Toxins

46 KiB

Open AccessRetraction

Retraction: Reddy, K.R.N.; Abbas, H.K.; Abel, C.A.; Shier, W.T.; Salleh, B. Mycotoxin Contamination of Beverages: Occurrence of Patulin in Apple Juice and Ochratoxin A in Coffee, Beer and Wine and Their Control Methods. Toxins 2010, 2, 229-261.

by Florian Lang and Shu-Kun Lin

Toxins 2010, 2(4), 934; https://doi.org/10.3390/toxins2040934 - 28 Apr 2010

Viewed by 7902

Abstract

It has been brought to our attention by a member of our Editorial Board that substantial portions of this review article have been copied verbatim from earlier publications without credit. After comparing the present paper and the other sources we have determined that [...] Read more.

It has been brought to our attention by a member of our Editorial Board that substantial portions of this review article have been copied verbatim from earlier publications without credit. After comparing the present paper and the other sources we have determined that indeed this manuscript clearly violates our policy on originality of all material submitted for publication and the generally accepted ethics of scientific publication. Consequently, the Editorial Team and Publisher have determined that it should be retracted. We apologize for any inconvenience this may cause. Full article

128 KiB

Open AccessReview

Discovery and Characterization of Proteins Associated with Aflatoxin-Resistance: Evaluating Their Potential as Breeding Markers

by Robert L. Brown, Zhi-Yuan Chen, Marilyn Warburton, Meng Luo, Abebe Menkir, Ahmad Fakhoury and Deepak Bhatnagar

Toxins 2010, 2(4), 919-933; https://doi.org/10.3390/toxins2040919 - 26 Apr 2010

Cited by 29 | Viewed by 10806

Abstract

Host resistance has become a viable approach to eliminating aflatoxin contamination of maize since the discovery of several maize lines with natural resistance. However, to derive commercial benefit from this resistance and develop lines that can aid growers, markers need to be identified [...] Read more.

Host resistance has become a viable approach to eliminating aflatoxin contamination of maize since the discovery of several maize lines with natural resistance. However, to derive commercial benefit from this resistance and develop lines that can aid growers, markers need to be identified to facilitate the transfer of resistance into commercially useful genetic backgrounds without transfer of unwanted traits. To accomplish this, research efforts have focused on the identification of kernel resistance-associated proteins (RAPs) including the employment of comparative proteomics to investigate closely-related maize lines that vary in aflatoxin accumulation. RAPs have been identified and several further characterized through physiological and biochemical investigations to determine their causal role in resistance and, therefore, their suitability as breeding markers. Three RAPs, a 14 kDa trypsin inhibitor, pathogenesis-related protein 10 and glyoxalase I are being investigated using RNAi gene silencing and plant transformation. Several resistant lines have been subjected to QTL mapping to identify loci associated with the aflatoxin-resistance phenotype. Results of proteome and characterization studies are discussed. Full article

(This article belongs to the Special Issue Advances in Mycotoxin Research)

342 KiB

Open AccessReview

AIP56: A Novel Bacterial Apoptogenic Toxin

by Manuel T. Silva, Nuno M. S. Dos Santos and Ana Do Vale

Toxins 2010, 2(4), 905-918; https://doi.org/10.3390/toxins2040905 - 26 Apr 2010

Cited by 16 | Viewed by 10770

Abstract

Photobacterium damselae subsp. piscicida (Phdp) is a Gram-negative pathogen agent of an important fish septicemia. The key virulence factor of Phdp is the plasmid-encoded exotoxin AIP56, which is secreted by exponentially growing pathogenic strains. AIP56 has 520 amino acids including an [...] Read more.

Photobacterium damselae subsp. piscicida (Phdp) is a Gram-negative pathogen agent of an important fish septicemia. The key virulence factor of Phdp is the plasmid-encoded exotoxin AIP56, which is secreted by exponentially growing pathogenic strains. AIP56 has 520 amino acids including an N-terminal cleavable signal peptide of 23 amino acid residues, two cysteine residues and a zinc-binding region signature HEXXH that is typical of most zinc metallopeptidases. AIP56 induces in vitro and in vivo selective apoptosis of fish macrophages and neutrophils through a caspase-3 dependent mechanism that also involves caspase-8 and -9. In vivo, the AIP56-induced phagocyte apoptosis progresses to secondary necrosis with release of cytotoxic phagocyte molecules including neutrophil elastase. Fish injected with recombinant AIP56 die with a pathology similar to that seen in the natural infection. Full article

(This article belongs to the Special Issue Toxins from Aquatic Organisms)

► Show Figures

Figure 1

675 KiB

Open AccessReview

Marine Toxins: Chemistry, Toxicity, Occurrence and Detection, with Special Reference to the Dutch Situation

by Arjen Gerssen, Irene E. Pol-Hofstad, Marnix Poelman, Patrick P.J. Mulder, Hester J. Van den Top and Jacob De Boer

Toxins 2010, 2(4), 878-904; https://doi.org/10.3390/toxins2040878 - 23 Apr 2010

Cited by 139 | Viewed by 20455

Abstract

Various species of algae can produce marine toxins under certain circumstances. These toxins can then accumulate in shellfish such as mussels, oysters and scallops. When these contaminated shellfish species are consumed severe intoxication can occur. The different types of syndromes that can occur [...] Read more.

Various species of algae can produce marine toxins under certain circumstances. These toxins can then accumulate in shellfish such as mussels, oysters and scallops. When these contaminated shellfish species are consumed severe intoxication can occur. The different types of syndromes that can occur after consumption of contaminated shellfish, the corresponding toxins and relevant legislation are discussed in this review. Amnesic Shellfish Poisoning (ASP), Paralytic Shellfish Poisoning (PSP), Diarrheic Shellfish Poisoning (DSP) and Azaspiracid Shellfish Poisoning (AZP) occur worldwide, Neurologic Shellfish Poisoning (NSP) is mainly limited to the USA and New Zealand while the toxins causing DSP and AZP occur most frequently in Europe. The latter two toxin groups are fat-soluble and can therefore also be classified as lipophilic marine toxins. A detailed overview of the official analytical methods used in the EU (mouse or rat bioassay) and the recently developed alternative methods for the lipophilic marine toxins is given. These alternative methods are based on functional assays, biochemical assays and chemical methods. From the literature it is clear that chemical methods offer the best potential to replace the animal tests that are still legislated worldwide. Finally, an overview is given of the situation of marine toxins in The Netherlands. The rat bioassay has been used for monitoring DSP and AZP toxins in The Netherlands since the 1970s. Nowadays, a combination of a chemical method and the rat bioassay is often used. In The Netherlands toxic events are mainly caused by DSP toxins, which have been found in Dutch shellfish for the first time in 1961, and have reoccurred at irregular intervals and in varying concentrations. From this review it is clear that considerable effort is being undertaken by various research groups to phase out the animal tests that are still used for the official routine monitoring programs. Full article

(This article belongs to the Special Issue Toxins from Aquatic Organisms)

► Show Figures

Figure 1

267 KiB

Open AccessReview

The Double-Edged Sword of Autoimmunity: Lessons from Multiple Sclerosis

by Anne Lise K. Hestvik

Toxins 2010, 2(4), 856-877; https://doi.org/10.3390/toxins2040856 - 22 Apr 2010

Cited by 14 | Viewed by 12937

Abstract

The relationship between immune responses to self-antigens and autoimmune disease is unclear. In contrast to its animal model experimental autoimmune encephalomyelitis (EAE), which is driven by T cell responses to myelin antigens, the target antigen of the intrathecal immune response in multiple sclerosis [...] Read more.

The relationship between immune responses to self-antigens and autoimmune disease is unclear. In contrast to its animal model experimental autoimmune encephalomyelitis (EAE), which is driven by T cell responses to myelin antigens, the target antigen of the intrathecal immune response in multiple sclerosis (MS) has not been identified. Although the immune response in MS contributes significantly to tissue destruction, the action of immunocompetent cells within the central nervous system (CNS) may also hold therapeutic potential. Thus, treatment of MS patients with glatiramer acetate triggers a protective immune response. Here we review the immunopathogenesis of MS and some recent findings on the mechanism of glatiramer acetate (GA). Full article

(This article belongs to the Collection Toxicity and Therapeutic Interventions in the Immune System)

► Show Figures

Figure 1

373 KiB

Open AccessArticle

Occurrence of Black Aspergilli and Ochratoxin A on Grapes in Italy

by Gianluca Lucchetta, Irene Bazzo, Gianluca Dal Cortivo, Lisa Stringher, Diego Bellotto, Michele Borgo and Elisa Angelini

Toxins 2010, 2(4), 840-855; https://doi.org/10.3390/toxins2040840 - 21 Apr 2010

Cited by 33 | Viewed by 10102

Abstract

Ochratoxin A (OTA) in wine is linked to contamination by several Aspergillus species. In 2003–2007, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producing fungi. A. niger aggregate was the prevalent species. A. carbonarius, which is considered [...] Read more.

Ochratoxin A (OTA) in wine is linked to contamination by several Aspergillus species. In 2003–2007, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producing fungi. A. niger aggregate was the prevalent species. A. carbonarius, which is considered the main source of OTA in grapes, was mostly found in Southern Italy. The year and the environment had an important influence on the development of the black Aspergillus populations. Testing with ELISA showed OTA to be present in about 30% of the samples. Samples from Southern Italy showed the highest occurrence (45%) and also the highest OTA concentration, sometimes higher than 2 mg/L. The values decreased progressively the further North the samples were taken. Full article

(This article belongs to the Special Issue Ochratoxins)

► Show Figures

Figure 1

364 KiB

Open AccessReview

Ochratoxin A in Ruminants–A Review on Its Degradation by Gut Microbes and Effects on Animals

by Muhammad Mobashar, Jürgen Hummel, Ralf Blank and Karl-Heinz Südekum

Toxins 2010, 2(4), 809-839; https://doi.org/10.3390/toxins204809 - 21 Apr 2010

Cited by 48 | Viewed by 12206

Abstract

Ruminants are much less sensitive to ochratoxin A (OTA) than non-ruminants. The ruminal microbes, with protozoa being a central group, degrade the mycotoxin extensively, with disappearance half lives of 0.6–3.8 h. However, in some studies OTA was detected systemically when using sensitive analytical [...] Read more.

Ruminants are much less sensitive to ochratoxin A (OTA) than non-ruminants. The ruminal microbes, with protozoa being a central group, degrade the mycotoxin extensively, with disappearance half lives of 0.6–3.8 h. However, in some studies OTA was detected systemically when using sensitive analytical methods, probably due to some rumen bypass at proportions of estimated 2–6.5% of dosage (maximum 10%). High concentrate proportions and high feeding levels are dietary factors promoting the likeliness of systemic occurrence due to factors like shifts in microbial population and higher contamination potential. Among risk scenarios for ruminants, chronic intoxication represents the most relevant. Full article

(This article belongs to the Special Issue Ochratoxins)

285 KiB

Open AccessReview

Fibrolase: Trials and Tribulations

by Francis S. Markland and Steve Swenson

Toxins 2010, 2(4), 793-808; https://doi.org/10.3390/toxins2040793 - 20 Apr 2010

Cited by 21 | Viewed by 10139

Abstract

Fibrolase is the fibrinolytic enzyme isolated from Agkistrodon contortrix contortrix (southern copperhead snake) venom. The enzyme was purified by a three-step HPLC procedure and was shown to be homogeneous by standard criteria including reverse phase HPLC, molecular sieve chromatography and SDS-PAGE. The purified [...] Read more.

Fibrolase is the fibrinolytic enzyme isolated from Agkistrodon contortrix contortrix (southern copperhead snake) venom. The enzyme was purified by a three-step HPLC procedure and was shown to be homogeneous by standard criteria including reverse phase HPLC, molecular sieve chromatography and SDS-PAGE. The purified enzyme is a zinc metalloproteinase containing one mole of zinc. It is composed of 203 amino acids with a blocked amino-terminus due to cyclization of the terminal Gln residue. Fibrolase shares a significant degree of homology with enzymes of the reprolysin sub-family of metalloproteinases including an active site homology of close to 100%; it is rapidly inhibited by chelating agents such as EDTA, and by alpha2-macroglobulin (α2M). The enzyme is a direct-acting thrombolytic agent and does not rely on plasminogen for clot dissolution. Fibrolase rapidly cleaves the A(α)-chain of fibrinogen and the B(β)-chain at a slower rate; it has no activity on the γ-chain. The enzyme exhibits the same specificity with fibrin, cleaving the α-chain more rapidly than the β-chain. Fibrolase was shown to have very effective thrombolytic activity in a reoccluding carotid arterial thrombosis model in the canine. A recombinant version of the enzyme was made in yeast by Amgen, Inc. (Thousand Oaks, CA, USA) and called alfimeprase. Alfimeprase is identical to fibrolase except for a two amino acid truncation at the amino-terminus and the insertion of a new amino-terminal amino acid in the truncated protein; these changes lead to a more stable enzyme for prolonged storage. Alfimeprase was taken into clinical trials by Nuvelo, Inc. (San Carlos, CA), which licensed the enzyme from Amgen. Alfimeprase was successful in Phase I and II clinical trials for peripheral arterial occlusion (PAO) and central venous access device (CVAD) occlusion. However, in Phase III trials alfimeprase did not meet the expected end points in either PAO or CVAD occlusion and in a Phaase II stroke trial, and Nuvelo dropped further development in 2008. Full article

(This article belongs to the Special Issue Animal Venoms)

► Show Figures

Figure 1

166 KiB

Open AccessArticle

Ochratoxin A and β2-Microglobulin in BEN Patients and Controls

by Pavlina Yordanova, Karmaus Wilfried, Svetla Tsolova and Plamen Dimitrov

Toxins 2010, 2(4), 780-792; https://doi.org/10.3390/toxins2040780 - 20 Apr 2010

Cited by 10 | Viewed by 9968

Abstract

Ochratoxin A (OTA) is a mycotoxin naturally occurring in different foods. OTA is arguably a risk factor for Balkan endemic nephropathy (BEN). The aims of this study are to (1) test the OTA-BEN association in BEN-groups and controls and (2) determine whether urine [...] Read more.

Ochratoxin A (OTA) is a mycotoxin naturally occurring in different foods. OTA is arguably a risk factor for Balkan endemic nephropathy (BEN). The aims of this study are to (1) test the OTA-BEN association in BEN-groups and controls and (2) determine whether urine β2-microglobulin, a marker of impaired ability of the kidneys to re-absorb, is related to OTA. BEN patients had significantly higher OTA serum levels. Within the offspring, OTA was significantly related to higher β2-microglobulin excretion. OTA (2005/2006) was related to a higher incidence of BEN after 2008, providing further evidence that OTA is a risk factor for BEN. Full article

(This article belongs to the Special Issue Ochratoxins)

266 KiB

Open AccessReview

Ochratoxins—Food Contaminants: Impact on Human Health

by Lalini Reddy and Kanti Bhoola

Toxins 2010, 2(4), 771-779; https://doi.org/10.3390/toxins2040771 - 20 Apr 2010

Cited by 120 | Viewed by 25314

Abstract

Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half-life in humans and is thus [...] Read more.

Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half-life in humans and is thus easily detected in serum. Dietary intake studies have confirmed link between endemic nephrotoxicity in humans to their daily household intake of OTA. OTA has been reported to contribute to endemic nephrotoxicity and carcinogenicity in humans and animals. OTA produces renal tumours, DNA adducts and chromosomal aberrations in kidneys. OTA may be embryotoxic, teratogenic, and immunotoxic only at doses higher than those causing nephrotoxicity. The incidence of endemic nephrotoxicity has been mostly reported in northeast Europe since the early fifties. Recent studies however have warned that OTA and other toxins, such as aristolochic acid, show very similar renal pathology. There is thus the need for thorough co-occurrence studies on toxin incidence. Full article

(This article belongs to the Special Issue Ochratoxins)

► Show Figures

Figure 1

226 KiB

Open AccessArticle

Ochratoxin A and Aflatoxins in Liquorice Products

by Amedeo Pietri, Silvia Rastelli and Terenzio Bertuzzi

Toxins 2010, 2(4), 758-770; https://doi.org/10.3390/toxins2040758 - 20 Apr 2010

Cited by 30 | Viewed by 10023

Abstract

The occurrence of ochratoxin A (OTA) and aflatoxins (AFs) in liquorice products made in Italy was surveyed. Twenty-eight samples of dried liquorice extract and fifty-four of liquorice confectionery (liquorice content between 2 and 10%) were collected from retail outlets located in northern Italy. [...] Read more.

The occurrence of ochratoxin A (OTA) and aflatoxins (AFs) in liquorice products made in Italy was surveyed. Twenty-eight samples of dried liquorice extract and fifty-four of liquorice confectionery (liquorice content between 2 and 10%) were collected from retail outlets located in northern Italy. After extraction and purification through an immunoaffinity column, OTA and AFs were analysed using both HPLC-FLD and HPLC-MS/MS. OTA occurred in all samples of dried liquorice extract and in 61% of samples of liquorice confectionery, showing very high values for the former (mean 89.6 µg kg^-1, maximum value 990.1 µg kg^-1), and relatively low levels for the latter (mean 0.96 µg kg^-1, maximum value 8.3 µg kg^-1). The contribution of dried liquorice extract to OTA intake appears to be non-negligible for children, who are potentially high consumers. AF contamination resulted very low: AFB₁ was detected only in 15.8% of samples (maximum value 7.7 µg kg^-1, mean 0.38 and 0.41 µg kg^-1 for dried liquorice extract and liquorice confectionery, respectively); the other AFs were not detected. To our knowledge, it is the first time that AFB₁ has been detected in liquorice extract samples. Full article

(This article belongs to the Special Issue Ochratoxins)

► Show Figures

Figure 1

204 KiB

Open AccessReview

Antigenotoxic Studies of Different Substances to Reduce the DNA Damage Induced by Aflatoxin B₁ and Ochratoxin A

by Eduardo Madrigal-Santillán, José A. Morales-González, Nancy Vargas-Mendoza, Patricia Reyes-Ramírez, Sandra Cruz-Jaime, Teresa Sumaya-Martínez, Ricardo Pérez-Pastén and Eduardo Madrigal-Bujaidar

Toxins 2010, 2(4), 738-757; https://doi.org/10.3390/toxins2040738 - 19 Apr 2010

Cited by 32 | Viewed by 12105

Abstract

Mycotoxins are produced mainly by the mycelial structure of filamentous fungi, or more specifically, molds. These secondary metabolites are synthesized during the end of the exponential growth phase and appear to have no biochemical significance in fungal growth and development. The contamination of [...] Read more.

Mycotoxins are produced mainly by the mycelial structure of filamentous fungi, or more specifically, molds. These secondary metabolites are synthesized during the end of the exponential growth phase and appear to have no biochemical significance in fungal growth and development. The contamination of foods and feeds with mycotoxins is a significant problem for the adverse effects on humans, animals, and crops that result in illnesses and economic losses. The toxic effect of the ingestion of mycotoxins in humans and animals depends on a number of factors including intake levels, duration of exposure, toxin species, mechanisms of action, metabolism, and defense mechanisms. In general, the consumption of contaminated food and feed with mycotoxin induces to neurotoxic, immunosuppressive, teratogenic, mutagenic, and carcinogenic effect in humans and/or animals. The most significant mycotoxins in terms of public health and agronomic perspective include the aflatoxins, ochratoxin A (OTA), trichothecenes, fumonisins, patulin, and the ergot alkaloids. Due to the detrimental effects of these mycotoxins, several strategies have been developed in order to reduce the risk of exposure. These include the degradation, destruction, inactivation or removal of mycotoxins through chemical, physical and biological methods. However, the results obtained with these methods have not been optimal, because they may change the organoleptic characteristics and nutritional values of food. Another alternative strategy to prevent or reduce the toxic effects of mycotoxins is by applying antimutagenic agents. These substances act according to several extra- or intracellular mechanisms, their main goal being to avoid the interaction of mycotoxins with DNA; as a consequence of their action, these agents would inhibit mutagenesis and carcinogenesis. This article reviews the main strategies used to control AFB₁ and ochratoxin A and contains an analysis of some antigenotoxic substances that reduce the DNA damage caused by these mycotoxins. Full article

► Show Figures

Graphical abstract

997 KiB

Open AccessReview

Bacterial Toxins and the Nervous System: Neurotoxins and Multipotential Toxins Interacting with Neuronal Cells

by Michel R. Popoff and Bernard Poulain

Toxins 2010, 2(4), 683-737; https://doi.org/10.3390/toxins2040683 - 15 Apr 2010

Cited by 91 | Viewed by 20518

Abstract

Toxins are potent molecules used by various bacteria to interact with a host organism. Some of them specifically act on neuronal cells (clostridial neurotoxins) leading to characteristics neurological affections. But many other toxins are multifunctional and recognize a wider range of cell types [...] Read more.

Toxins are potent molecules used by various bacteria to interact with a host organism. Some of them specifically act on neuronal cells (clostridial neurotoxins) leading to characteristics neurological affections. But many other toxins are multifunctional and recognize a wider range of cell types including neuronal cells. Various enterotoxins interact with the enteric nervous system, for example by stimulating afferent neurons or inducing neurotransmitter release from enterochromaffin cells which result either in vomiting, in amplification of the diarrhea, or in intestinal inflammation process. Other toxins can pass the blood brain barrier and directly act on specific neurons. Full article

(This article belongs to the Special Issue Neurotoxins of Biological Origin)

► Show Figures

Figure 1

375 KiB

Open AccessReview

Clostridial Neurotoxins: Mechanism of SNARE Cleavage and Outlook on Potential Substrate Specificity Reengineering

by Thomas Binz, Stefan Sikorra and Stefan Mahrhold

Toxins 2010, 2(4), 665-682; https://doi.org/10.3390/toxins2040665 - 13 Apr 2010

Cited by 57 | Viewed by 13506

Abstract

The clostridial neurotoxin family consists of tetanus neurotoxin and seven distinct botulinum neurotoxins which cause the diseases tetanus and botulism. The extreme potency of these toxins primarily relies not only on their ability to specifically enter motoneurons but also on the activity their [...] Read more.

The clostridial neurotoxin family consists of tetanus neurotoxin and seven distinct botulinum neurotoxins which cause the diseases tetanus and botulism. The extreme potency of these toxins primarily relies not only on their ability to specifically enter motoneurons but also on the activity their catalytic domains display inside presynaptic motoneuronal terminals. Subsequent to neurotoxin binding and endocytosis the catalytic domains become translocated across endosomal membranes and proteolyze unique peptide bonds of one of three soluble N-ethylmaleimide-sensitive fusion protein attachment receptors (SNAREs), vesicle associated membrane protein/synaptobrevin, synaptosome associated protein of 25 kDa, or syntaxin. As these substrate proteins are core components of the vesicular membrane fusion apparatus, cleavage of any of the substrate molecules results in the blockade of neurotransmitter release. This review summarizes the present knowledge about the molecular basis of the specific substrate recognition and cleavage mechanism and assesses the feasibility of reengineering catalytic domains to hydrolyze non-substrate members of the three SNARE families in order to expand the therapeutic application of botulinum neurotoxins. Full article

(This article belongs to the Special Issue Bacterial Protein Toxins)

► Show Figures

Figure 1

442 KiB

Open AccessArticle

Studies on Carcinogenic and Toxic Effects of Ochratoxin A in Chicks

by Stoycho D. Stoev

Toxins 2010, 2(4), 649-664; https://doi.org/10.3390/toxins2040649 - 12 Apr 2010

Cited by 69 | Viewed by 11863

Abstract

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm [...] Read more.

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm OTA, which showed that PHE cannot be used as a real protector against the carcinogenic or toxic effects of OTA in chicks. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver. Full article

(This article belongs to the Special Issue Ochratoxins)

► Show Figures

Graphical abstract

2338 KiB

Open AccessArticle

The Effects of Cholera Toxin on Cellular Energy Metabolism

by Rachel M. Snider, Jennifer R. McKenzie, Lewis Kraft, Eugene Kozlov, John P. Wikswo and David E. Cliffel

Toxins 2010, 2(4), 632-648; https://doi.org/10.3390/toxins2040632 - 8 Apr 2010

Cited by 20 | Viewed by 10774

Abstract

Multianalyte microphysiometry, a real-time instrument for simultaneous measurement of metabolic analytes in a microfluidic environment, was used to explore the effects of cholera toxin (CTx). Upon exposure of CTx to PC-12 cells, anaerobic respiration was triggered, measured as increases in acid and lactate [...] Read more.

Multianalyte microphysiometry, a real-time instrument for simultaneous measurement of metabolic analytes in a microfluidic environment, was used to explore the effects of cholera toxin (CTx). Upon exposure of CTx to PC-12 cells, anaerobic respiration was triggered, measured as increases in acid and lactate production and a decrease in the oxygen uptake. We believe the responses observed are due to a CTx-induced activation of adenylate cyclase, increasing cAMP production and resulting in a switch to anaerobic respiration. Inhibitors (H-89, brefeldin A) and stimulators (forskolin) of cAMP were employed to modulate the CTx-induced cAMP responses. The results of this study show the utility of multianalyte microphysiometry to quantitatively determine the dynamic metabolic effects of toxins and affected pathways. Full article

(This article belongs to the Special Issue Feature Papers)

► Show Figures

Figure 1

380 KiB

Open AccessReview

Biosynthesis and Toxicological Effects of Patulin

by Olivier Puel, Pierre Galtier and Isabelle P. Oswald

Toxins 2010, 2(4), 613-631; https://doi.org/10.3390/toxins2040613 - 5 Apr 2010

Cited by 454 | Viewed by 32594

Abstract

Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young [...] Read more.

Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes. Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. The biosynthetic pathway consists of approximately 10 steps, as suggested by biochemical studies. Recently, a cluster of 15 genes involved in patulin biosynthesis was reported, containing characterized enzymes, a regulation factor and transporter genes. This review includes information on the current understanding of the mechanisms of patulin toxinogenesis and summarizes its toxicological effects. Full article

(This article belongs to the Special Issue Advances in Mycotoxin Research)

► Show Figures

Figure 1

546 KiB

Open AccessReview

Biological Profile of Erucin: A New Promising Anticancer Agent from Cruciferous Vegetables

by Antonietta Melchini and Maria H. Traka

Toxins 2010, 2(4), 593-612; https://doi.org/10.3390/toxins2040593 - 5 Apr 2010

Cited by 87 | Viewed by 15191

Abstract

Consumption of cruciferous vegetables has been associated with a reduced risk in the development of various types of cancer. This has been attributed to the bioactive hydrolysis products that are derived from these vegetables, namely isothiocyanates. Erucin is one such product derived from [...] Read more.

Consumption of cruciferous vegetables has been associated with a reduced risk in the development of various types of cancer. This has been attributed to the bioactive hydrolysis products that are derived from these vegetables, namely isothiocyanates. Erucin is one such product derived from rocket salads, which is structurally related to sulforaphane, a well-studied broccoli-derived isothiocyanate. In this review, we present current knowledge on mechanisms of action of erucin in chemoprevention obtained from cell and animal models and relate it to other isothiocyanates. These mechanisms include modulation of phase I, II and III detoxification, regulation of cell growth by induction of apoptosis and cell cycle arrest, induction of ROS-mechanisms and regulation androgen receptor pathways. Full article

(This article belongs to the Special Issue Can Botanical Toxins Enhance Human Health?)

► Show Figures

Figure 1

522 KiB

Open AccessReview

Real and Perceived Risks for Mycotoxin Contamination in Foods and Feeds: Challenges for Food Safety Control

by Dragan R. Milićević, Marija Škrinjar and Tatjana Baltić

Toxins 2010, 2(4), 572-592; https://doi.org/10.3390/toxins2040572 - 1 Apr 2010

Cited by 224 | Viewed by 19972

Abstract

Mycotoxins are toxic compounds, produced by the secondary metabolism of toxigenic moulds in the Aspergillus, Alternaria, Claviceps, Fusarium, Penicillium and Stachybotrys genera occurring in food and feed commodities both pre- and post-harvest. Adverse human health effects from the consumption [...] Read more.

Mycotoxins are toxic compounds, produced by the secondary metabolism of toxigenic moulds in the Aspergillus, Alternaria, Claviceps, Fusarium, Penicillium and Stachybotrys genera occurring in food and feed commodities both pre- and post-harvest. Adverse human health effects from the consumption of mycotoxins have occurred for many centuries. When ingested, mycotoxins may cause a mycotoxicosis which can result in an acute or chronic disease episode. Chronic conditions have a much greater impact, numerically, on human health in general, and induce diverse and powerful toxic effects in test systems: some are carcinogenic, mutagenic, teratogenic, estrogenic, hemorrhagic, immunotoxic, nephrotoxic, hepatotoxic, dermotoxic and neurotoxic. Although mycotoxin contamination of agricultural products still occurs in the developed world, the application of modern agricultural practices and the presence of a legislatively regulated food processing and marketing system have greatly reduced mycotoxin exposure in these populations. However, in developing countries, where climatic and crop storage conditions are frequently conducive to fungal growth and mycotoxin production, much of the population relies on subsistence farming or on unregulated local markets. Therefore both producers and governmental control authorities are directing their efforts toward the implementation of a correct and reliable evaluation of the real status of contamination of a lot of food commodity and, consequently, of the impact of mycotoxins on human and animal health. Full article

(This article belongs to the Special Issue Advances in Mycotoxin Research)

► Show Figures

Figure 1

1277 KiB

Open AccessArticle

Oncological Outcomes in Rats Given Nephrocarcinogenic Exposure to Dietary Ochratoxin A, Followed by the Tumour Promoter Sodium Barbital for Life: A Pilot Study

by Peter G. Mantle, Miloslav Dobrota, Cheryl E. Gillett, Edward W. Odell and Sarah E. Pinder

Toxins 2010, 2(4), 552-571; https://doi.org/10.3390/toxins2040552 - 31 Mar 2010

Cited by 9 | Viewed by 9680

Abstract

The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young [...] Read more.

The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young rats, of a hybrid in which mononuclear leukaemia was rare, were given feed contaminated (5 ppm) with OTA for 36 weeks to initiate renal tumourigenesis. Some individuals were thereafter given sodium barbitate (500 ppm in drinking water) for life. Pathological outcomes were studied at or near the end of natural life. Renal tumours in males given barbitate became evident after latency of one year, but only slightly before those without barbitate. In contrast, female mammary tumourigenesis was advanced by at least 6 months synchronously in all rats given the OTA-barbitate regimen compared to tumourigenesis in controls. Diagnosis of malignant mammary angiosarcoma in a female given the OTA-barbitate regimen is a new finding in the rat. The long latency of OTA-induced renal tumourigenesis was not notably susceptible to accelerated promotion by barbitate, contrasting with an apparently marked effect of barbitate on development of mammary tumours. Full article

(This article belongs to the Special Issue Ochratoxins)

► Show Figures

Graphical abstract

196 KiB

Open AccessReview

Phytochemicals in Cancer Prevention and Therapy: Truth or Dare?

by Maria Russo, Carmela Spagnuolo, Idolo Tedesco and Gian Luigi Russo

Toxins 2010, 2(4), 517-551; https://doi.org/10.3390/toxins2040517 - 31 Mar 2010

Cited by 180 | Viewed by 15565

Abstract

A voluminous literature suggests that an increase in consumption of fruit and vegetables is a relatively easy and practical strategy to reduce significantly the incidence of cancer. The beneficial effect is mostly associated with the presence of phytochemicals in the diet. This review [...] Read more.

A voluminous literature suggests that an increase in consumption of fruit and vegetables is a relatively easy and practical strategy to reduce significantly the incidence of cancer. The beneficial effect is mostly associated with the presence of phytochemicals in the diet. This review focuses on a group of them, namely isothiocyanate, curcumin, genistein, epigallocatechin gallate, lycopene and resveratrol, largely studied as chemopreventive agents and with potential clinical applications. Cellular and animal studies suggest that these molecules induce apoptosis and arrest cell growth by pleiotropic mechanisms. The anticancer efficacy of these compounds may result from their use in monotherapy or in association with chemotherapeutic drugs. This latter approach may represent a new pharmacological strategy against several types of cancers. However, despite the promising results from experimental studies, only a limited number of clinical trials are ongoing to assess the therapeutic efficacy of these molecules. Nevertheless, the preliminary results are promising and raise solid foundations for future investigations. Full article

(This article belongs to the Special Issue Natural Products for Multi-Targeted Cancer Treatment: Where Are We Now?)

642 KiB

Open AccessReview

Venom Proteins of the Parasitoid Wasp Nasonia vitripennis: Recent Discovery of an Untapped Pharmacopee

by Ellen L. Danneels, David B. Rivers and Dirk C. De Graaf

Toxins 2010, 2(4), 494-516; https://doi.org/10.3390/toxins2040494 - 30 Mar 2010

Cited by 92 | Viewed by 16061

Abstract

Adult females of Nasonia vitripennis inject a venomous mixture into its host flies prior to oviposition. Recently, the entire genome of this ectoparasitoid wasp was sequenced, enabling the identification of 79 venom proteins. The next challenge will be to unravel their specific functions, [...] Read more.

Adult females of Nasonia vitripennis inject a venomous mixture into its host flies prior to oviposition. Recently, the entire genome of this ectoparasitoid wasp was sequenced, enabling the identification of 79 venom proteins. The next challenge will be to unravel their specific functions, but based on homolog studies, some predictions already can be made. Parasitization has an enormous impact on hosts physiology of which five major effects are discussed in this review: the impact on immune responses, induction of developmental arrest, increases in lipid levels, apoptosis and nutrient releases. The value of deciphering this venom is also discussed. Full article

(This article belongs to the Special Issue Animal Venoms)

► Show Figures

Figure 1

552 KiB

Open AccessReview

Ochratoxin A: General Overview and Actual Molecular Status

by André El Khoury and Ali Atoui

Toxins 2010, 2(4), 461-493; https://doi.org/10.3390/toxins2040461 - 29 Mar 2010

Cited by 356 | Viewed by 26348

Abstract

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show [...] Read more.

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show that this molecule can have several toxicological effects such as nephrotoxic, hepatotoxic, neurotoxic, teratogenic and immunotoxic. A role in the etiology of Balkan endemic nephropathy and its association to urinary tract tumors has been also proved. In this review, we will explore the general aspect of OTA: physico-chemical properties, toxicological profile, OTA producing fungi, contaminated food, regulation, legislation and analytical methods. Due to lack of sufficient information related to the molecular background, this paper will discuss in detail the recent advances in molecular biology of OTA biosynthesis, based on information and on new data about identification and characterization of ochratoxin biosynthetic genes in both Penicillium and Aspergillus species. This review will also cover the development of the molecular methods for the detection and quantification of OTA producing fungi in various foodstuffs. Full article

(This article belongs to the Special Issue Ochratoxins)

► Show Figures

Figure 1

274 KiB

Open AccessArticle

Effects of Aflatoxin B₁ and Fumonisin B₁ on Blood Biochemical Parameters in Broilers

by Eliana N. C. Tessari, Estela Kobashigawa, Ana Lúcia S. P. Cardoso, David R. Ledoux, George E. Rottinghaus and Carlos A. F. Oliveira

Toxins 2010, 2(4), 453-460; https://doi.org/10.3390/toxins2040453 - 29 Mar 2010

Cited by 51 | Viewed by 11126

Abstract

The individual and combined effects of dietary aflatoxin B₁(AFB₁) and fumonisin B₁ (FB₁) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days [...] Read more.

The individual and combined effects of dietary aflatoxin B₁(AFB₁) and fumonisin B₁ (FB₁) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days of age. Dietary treatments included a 3 × 3 factorial arrangement with three levels of AFB₁(0, 50 and 200 μg AFB₁/kg), and three levels of FB₁(0, 50 and 200 mg FB₁/kg). At 33 days post feeding, with the exception of birds fed 50 mg FB₁only, concentrations of AST were higher (p < 0.05) in all other treatment groups when compared with controls. Plasma TP was lower (p < 0.05) at six days post feeding in groups fed 200 mgAFB₁/kg alone or in combination with FB₁. At day 33 days post feeding, with the exception of birds fed the highest combination of AFB₁and FB₁which had higher plasma TP than control birds_,plasma TP of birds fed other dietary treatments were similar to controls. Broilers receiving the highest levels of AFB₁ and FB₁ had bile duct proliferation and trabecular disorder in liver samples. AFB₁ singly or in combination with FB at the levels studied, caused liver damage and an increase in serum levels of AST. Full article

(This article belongs to the Special Issue Feature Papers)

► Show Figures

Figure 1

430 KiB

Open AccessReview

Toxins–Useful Biochemical Tools for Leukocyte Research

by Susana Cubillos, Johannes Norgauer and Katja Lehmann

Toxins 2010, 2(4), 428-452; https://doi.org/10.3390/toxins2040428 - 26 Mar 2010

Cited by 9 | Viewed by 11480

Abstract

Leukocytes are a heterogeneous group of cells that display differences in anatomic localization, cell surface phenotype, and function. The different subtypes include e.g., granulocytes, monocytes, dendritic cells, T cells, B cells and NK cells. These different cell types represent the cellular component of [...] Read more.

Leukocytes are a heterogeneous group of cells that display differences in anatomic localization, cell surface phenotype, and function. The different subtypes include e.g., granulocytes, monocytes, dendritic cells, T cells, B cells and NK cells. These different cell types represent the cellular component of innate and adaptive immunity. Using certain toxins such as pertussis toxin, cholera toxin or clostridium difficile toxin, the regulatory functions of Gα_i, Gαs and small GTPases of the Rho family in leukocytes have been reported. A summary of these reports is discussed in this review. Full article

(This article belongs to the Collection Toxicity and Therapeutic Interventions in the Immune System)

► Show Figures

Graphical abstract

144 KiB

Open AccessReview

Inhibition of Hemorragic Snake Venom Components: Old and New Approaches

by Isabella Panfoli, Daniela Calzia, Silvia Ravera and Alessandro Morelli

Toxins 2010, 2(4), 417-427; https://doi.org/10.3390/toxins2040417 - 25 Mar 2010

Cited by 35 | Viewed by 11447

Abstract

Snake venoms are complex toxin mixtures. Viperidae and Crotalidae venoms, which are hemotoxic, are responsible for most of the envenomations around the world. Administration of antivenins aimed at the neutralization of toxins in humans is prone to potential risks. Neutralization of snake venom [...] Read more.

Snake venoms are complex toxin mixtures. Viperidae and Crotalidae venoms, which are hemotoxic, are responsible for most of the envenomations around the world. Administration of antivenins aimed at the neutralization of toxins in humans is prone to potential risks. Neutralization of snake venom toxins has been achieved through different approaches: plant extracts have been utilized in etnomedicine. Direct electric current from low voltage showed neutralizing properties against venom phospholipase A2 and metalloproteases. This mini-review summarizes new achievements in venom key component inhibition. A deeper knowledge of alternative ways to inhibit venom toxins may provide supplemental treatments to serum therapy. Full article

(This article belongs to the Special Issue Animal Venoms)

800 KiB

Open AccessArticle

The Black Aspergillus Species of Maize and Peanuts and Their Potential for Mycotoxin Production

by Edwin R. Palencia, Dorothy M. Hinton and Charles W. Bacon

Toxins 2010, 2(4), 399-416; https://doi.org/10.3390/toxins2040399 - 24 Mar 2010

Cited by 74 | Viewed by 14311

Abstract

The black spored fungi of the subgenera Circumdata,the section Nigri (=Aspergillus niger group) is reviewed relative to their production of mycotoxins and their effects on plants as pathogens. Molecular methods have revealed more than 18 cryptic species, of which several have been [...] Read more.

The black spored fungi of the subgenera Circumdata,the section Nigri (=Aspergillus niger group) is reviewed relative to their production of mycotoxins and their effects on plants as pathogens. Molecular methods have revealed more than 18 cryptic species, of which several have been characterized as potential mycotoxin producers. Others are defined as benign relative to their ability to produce mycotoxins. However, these characterizations are based on in vitro culture and toxins production. Several can produce the ochratoxins that are toxic to livestock, poultry, and humans. The black aspergilli produce rots of grapes, maize, and numerous other fruits and grain and they are generally viewed as post-harvest pathogens. Data are review to suggest that black aspergilli, as so many others, are symptomless endophytes. These fungi and their mycotoxins contaminate several major grains, foodstuffs, and products made from them such as wine, and coffee. Evidence is presented that the black aspergilli are producers of other classes of mycotoxins such as the fumonisins, which are known carcinogenic and known prior investigations as being produced by the Fusarium species. Three species are identified in U.S. maize and peanuts as symptomless endophytes, which suggests the potential for concern as pathogens and as food safety hazards. Full article

(This article belongs to the Special Issue Advances in Mycotoxin Research)

► Show Figures

Figure 1

361 KiB

Open AccessArticle

Development of an Electrochemical Immunosensor for Fumonisins Detection in Foods

by Mohamad Kamal Abdul Kadir and Ibtisam E. Tothill

Toxins 2010, 2(4), 382-398; https://doi.org/10.3390/toxins2040382 - 24 Mar 2010

Cited by 51 | Viewed by 11490

Abstract

An electrochemical affinity sensor for the determination of fumonisins mycotoxins (Fms) using monoclonal antibody modified screen-printed gold electrode with carbon counter and silver-silver chloride pseudo-reference electrode is reported in this work. A direct competitive enzyme-linked immunosorbent assay (ELISA) was initially developed, exhibiting a [...] Read more.

An electrochemical affinity sensor for the determination of fumonisins mycotoxins (Fms) using monoclonal antibody modified screen-printed gold electrode with carbon counter and silver-silver chloride pseudo-reference electrode is reported in this work. A direct competitive enzyme-linked immunosorbent assay (ELISA) was initially developed, exhibiting a detection limit of 100 µg·L^-1for fumonisins. This was then transferred to the surface of a bare gold screen-printed electrode (SPGE) and detection was performed by chronoamperometry, monitoring the reaction of 3,3’,5,5’-Tetramethylbenzidine dihydrochloride (TMB) and hydrogen peroxide (H₂O₂) catalysed by HRP at −100 mV potential vs. onboard Ag-AgCl pseudo-reference electrode. The immunosensor exhibited detection limit of 5 µg·L⁻¹ fumonisins with a dynamic range from 1 µg·L⁻¹–1000 µg·L⁻¹. The sensor also performed well in extracted corn samples. Full article

(This article belongs to the Special Issue Advances in Mycotoxin Research)

► Show Figures

Figure 1

349 KiB

Open AccessReview

Role of the Osmotic Stress Regulatory Pathway in Morphogenesis and Secondary Metabolism in Filamentous Fungi

by Rocio Duran, Jeffrey W. Cary and Ana M. Calvo

Toxins 2010, 2(4), 367-381; https://doi.org/10.3390/toxins2040367 - 24 Mar 2010

Cited by 112 | Viewed by 15664

Abstract

Environmental stimuli trigger an adaptative cellular response to optimize the probability of survival and proliferation. In eukaryotic organisms from mammals to fungi osmotic stress, mainly through the action of the high osmolarity glycerol (HOG) pathway, leads to a response necessary for adapting and [...] Read more.

Environmental stimuli trigger an adaptative cellular response to optimize the probability of survival and proliferation. In eukaryotic organisms from mammals to fungi osmotic stress, mainly through the action of the high osmolarity glycerol (HOG) pathway, leads to a response necessary for adapting and surviving hyperosmotic environments. In this review we show that the osmoadaptative response is conserved but not identical in different fungi. The osmoadaptative response system is also intimately linked to morphogenesis in filamentous fungi, including mycotoxin producers. Previous studies indicate that the response to osmotic stress is also coupled to the biosynthesis of natural products, including mycotoxins. Full article

(This article belongs to the Special Issue Advances in Mycotoxin Research)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Toxins, Volume 2, Issue 4 (April 2010) – 29 articles , Pages 367-934

Further Information

Guidelines

MDPI Initiatives

Follow MDPI