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Opinion

Age-Related Diseases and Foods Generating Chlorinative Stress

by
Eleonora Di Salvo
1,
Marco Casciaro
2,*,
Concetto Mario Giorgianni
3,
Nicola Cicero
3,4 and
Sebastiano Gangemi
2
1
Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy
2
School and Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
3
Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, 98125 Messina, Italy
4
Science4life srl, Spin off Company, University of Messina, 98100 Messina, Italy
*
Author to whom correspondence should be addressed.
Antioxidants 2023, 12(2), 249; https://doi.org/10.3390/antiox12020249
Submission received: 16 November 2022 / Revised: 8 January 2023 / Accepted: 20 January 2023 / Published: 22 January 2023
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Abstract

:
Background: Aging is a slow and inexorable process affecting all life beings and is characterised by age-related worsening in adaptation to external changes. Several factors contribute to such a process, and oxidative stress due to external damages is one key player. Of particular interest is the oxidative stress generated from halogen compounds such as chloride. Hypochlorus acid is produced starting from MPO’s interaction with hydrogen peroxide. We focused on the oxidation of tyrosine residues by HOCl, which leads as a result to the formation of 3-chlorotyrosine (3-ClTyr). This molecule, due to its stability, is considered a marker for MPO activity. Results: We collected data from literature research articles evaluating chlorinative stress and the effects of 3-ClTyr on chronic diseases linked to aging. As diseases are not the only source of 3-ClTyr in people, we also focused on other origins of chlorinative stress, such as food intake. Discussion: Oxidation and halogenation are caused by infectious diseases and by pathologies characterised by inflammation. Moreover, diet could negatively or positively influence chlorinative stress. Comparing 3-ClTyr levels in the oldest and youngest old with age-related diseases and comparing data between different geographic areas with different pesticide rules could be the next challenge.

Graphical Abstract

1. Introduction

Aging is a slow and inexorable process affecting all life, being characterised by an increasing worsening in adaptation to external changes and in a growing difficulty to maintain body homeostasis due to a diminished renewal capacity by cells and tissues. Several factors contribute to such a process, and oxidative stress due to external damages is one key player. Oxidative stress can originate from an exaggerated response to biological agents, such as in infectious diseases. In fact, in the attempt to counteract external pathogens, the oxidative burst of immune system cells can become harmful. Reactive oxygen species (ROS), highly unstable oxidating molecules, can also be generated by a lack of antioxidant systems in chronic diseases such as diabetes, COPD, and autoimmune disease [1,2,3]. Of particular interest is the oxidative stress generated from halogen compounds such as chloride (Cl−).
During the life span, the human being undergoes inflammatory processes that involve myeloperoxidase (MPO) as a defense system. MPO has a weak antimicrobial activity, which is potentiated by the interaction with hydrogen peroxide. Native MPO is converted to MPO compound I, which can in turn start the “halogenation cycle” or the “peroxidation” one. Once the halogenation cycle is started, MPO compound I undergoes a two-electron reduction with halides/pseudohalides such as chloride (Cl−) to produce hypochlorous acid [4]. Instead, with the peroxidation cycle, MPO compound I, forming a MPO compound II complex, encounters two consecutive one-electron reductions, resulting in several radicals [5] (Figure 1).
MPO can work as a tool for many chemical reactions. Although it has such interchangeability, its main role is to produce hypochlorous acid (HOCl). HOCl is a powerful oxidating agent for biological agents. It can modify many biomolecules, such as DNA, lipids, and lipoproteins [6]. Of course, as an ROS, HOCl cannot stably maintain its form, so it interacts quickly with atoms of sulphur and nitrogen (nucleophile groups), typically present in thiols and thioethers (in cysteine and methionine residues), amines, and amides [7]. These interactions with thiol groups can deeply modify the biomolecules. The inactivation or activation of cellular enzymes such as metalloproteinases (MMPs) or proteinases can alter signalling cascades, compromising cell and tissue homeostasis [8]. Equally, the modification of amines and amides by HOCl generates chloramines and chloramides with detrimental cellular consequences.
Here, we focus on the oxidation of tyrosine residues by HOCl, which leads as a result to the formation of 3-chlorotyrosine (3-ClTyr). This molecule, due to its stability, is considered a marker for MPO activity (Figure 2) [9,10,11,12].
As mentioned above, 3-ClTyr is easy to detect in serum due to its stability, and reflects the oxidative stress status linked to MPO activity and HOCl presence. However, it is also responsible for a direct influence on human homeostasis, as reported by some authors on the cardiovascular system. MPO-mediated chlorination of HDL impairs the direct binding of HDL to the ATP-binding cassette transporter (ABCA1) responsible for removing the exceeding intracellular cholesterol from macrophages. As a direct consequence, chlorination contributes to atherogenesis. Moreover, free 3-ClTyr can lead to direct vascular lesion formation by promoting the migration of human aortic smooth muscle cells [13].
The action of 3-ClTyr on the cardiovascular system is only one of the potential detrimental effects of the molecule on human pathophysiology. For this reason, we decided to collect data from literature research articles evaluating chlorinative stress on and the effects of 3-ClTyr on chronic disease linked to aging. As diseases are not the only source of 3-ClTyr in people, we focused also on other origins of chlorinative stress, such as food intake.

2. Materials and Methods

We spanned literature from inception until 31 October 2022. We entered the terms “aging”, “elderly”, “oldest old”, “centenarians”, “nonagenarians”, and “octagenarians” together with “chlorinative stress”, “3-chlorotyrosine”, “HOCl”, “chlorine”, and “hypochlorous acid”. We selected only articles that were in English. First, we excluded articles whose title did not match with our topic. Then, we read the abstract and then the entire paper of the research articles, focusing on the role of chlorinative stress in patients aged 65 or above.

3. Results

A total of 13 research articles evaluating the correlation between chlorinative stress and age-related disease were collected from the literature (Table 1).

3.1. Neurodegenerative Diseases

Pena-Bautista et al. studied 53 patients with a mean age of 70 affected by Alzheimer’s. Patients’ urine levels did not show any significant differences regarding tyrosine chlorination (3-Cl-Tyr/p-Tyr) vs. age-matched healthy controls. The authors speculated that the chlorination product levels were below the limit of detection since the experiment was conducted on urine samples [14].
Garcia-Moreno et al. conducted their analysis on 60 patients affected by Parkinson’s disease with a mean age of 63. In these patients, 3-chlorotyrosine was not detected nor in serum or in cerebrospinal fluid [15].

3.2. Chronic Obstructive Pulmonary Disease (COPD)

O’Donnel et al. reported 3Cl-Tyr levels in 14 patients with a mean age of 65 affected by COPD. Their study presented some criticism, because in healthy patients it was particularly difficult to collect spontaneous sputum, with them being “healthy”. However, they demonstrated an intimate link between 3Cl-Tyr, neutrophil number, and MPO activity. Their data suggested a positive correlation between 3Cl-Tyr and lung inflammation [16].

3.3. Kidney Failure (KD)

Afshinnia et al. noticed a positive correlation between 3Cl-Tyr levels and a worse chronic KD stage in 23 patients with a mean age of 67. They also reported an independent link with coronary artery disease [17].
The association with kidney failure was further confirmed by Delporte et al., who reported 3Cl-Tyr augmented levels in 15 haemodialysis patients aged 77 [18].

3.4. Coronary Disease (CD)

Cheng et al. evaluated 77 patients with acute CD with a mean age of 65. 3-Cl-Tyr levels were importantly increased in patients with an acute myocardial infarction (MI) compared to normal controls [19].
Wang et al. did not find differences in HDL-3-ClTyr levels between a group of 20 patients aged 63 and healthy controls [20].
A similar trend was confirmed by research on serum on a group of 512 patients affected by MI with a mean age of 62 [21].
Shao et al. reported elevated serum 3-ClTyr in 20 patients with stable coronary disease aged 64 and in 20 patients with acute coronary syndrome aged 63 [22].

3.5. Colorectal Cancer (CRC)

A positive correlation of 3-ClTyr with CRC and with cancer stage was found in 75 patients with a mean age of 66 [23].

3.6. Rheumatoid Arthritis (RA) and Vasculitis

Stamp et al. reported that 3-ClTyr values in a group of 77 patients aged up to 82 years old were significantly augmented [24].
Another study by Vivekanandan-Giri et al. confirmed the trend, although the mean age in the 38 patients analysed was 63 [25].
Higashi et al. demonstrated a significant increase in 3-ClTyr in urine during the acute phase of the disease in eight patients affected by vasculitis with a mean age of 66 [26].

3.7. Brain Levels

Kato et al. analysed chlorinative stress in the aged brain in three patients with a mean age of 69 affected by aneurism, myocardial infarction, and lung cancer, respectively. In every case, 3-ClTyr was detectable [27].

4. Discussion

As discussed above, MPO activity and HOCl formation is a physiological event that affects all human beings. The main purpose of HOCl’s presence is its antimicrobial function. As happens for other ROSs, their presence is counterbalanced by a scavenging system and by the intervention of antioxidant body defences, which are mainly enzymatic. Chlorinative stress is a result of MPO activation. In every age-related disease mentioned above there is the activation of such an enzyme. Neutrophils, together with specific monocyte–macrophage line cells activate MPO and produce HOCl. MPO is a glycosylated haem enzyme deposited in neutrophils and macrophagous azurophilic granules; these granules have a powerful bactericidal action, which is due to the production of hypochlorous acid from hydrogen peroxide and chloride ions. MPO could be released extracellularly; augmented serum levels of MPO have been described in chronic inflammatory conditions typical of age-related diseases such as atherosclerosis, neurodegenerative conditions, and some cancers [28,29,30,31]. Oxidative and chlorinative stress are key features of aging. Age-related diseases are characterised by high ROS levels [32,33]. What distinguishes successful aging is the ability of the person not to undergo the oxidative stress and inflammation without counterbalancing it. It can happen that the oldest elderly have a coexisting condition of high inflammatory parameters but also an optimal anti-inflammatory counterbalance, guaranteeing long-lasting healthy status [34].
As we reported by spanning the literature, oxidation and halogenation are caused by infectious disease, but also happen in pathologies characterised by intense inflammatory status. A young subject can more easily face elevated ROS levels in cardiovascular, metabolic, or autoimmune diseases. As we report, often, aged people with such diseases suffer more chlorinative stress, which is testified by elevated 3-ClTyr levels. This compound could modify the proteins’ structure, compromising their optimal function. This is a worsening factor in such already detrimental diseases. Whichever is the source of HOCl, the result is more oxidative and chlorinative stress, and in turn, more inflammation. For this reason, reducing the levels of HOCl is one important step in reducing inflammaging. This goal can be reached in diverse manners. The lifestyle is one of the best options in a long-term period and is a variable of ease intervention by the patient itself.

Chlorinative Stress: Food, Help, or Threat?

In recent years, the close correlation between chlorination and diet has been demonstrated. Nevertheless, the use of chlorinated substances has been restricted in the instance of the Global Stockholm Convention (UNEP, 2004), both in Europe and the USA [35]. Until then, the most commonly used chlorinated substances were organic pesticides, used in the agrifood industry, such as dichlorodiphenyldichlorethylene (DDE), hexachlorbenzene (HCB) [36], and persistent organic pollutants (POPs). This set of toxic chemicals are persistent in the environment and able to last for several years because they accumulate in the fatty tissue of animals and humans, as well as in the ground [37]. Although the use of these substances has been forbidden, some studies have reported their presence in human tissues several times [38]. Children and foetuses are no exceptions [39]. However, epidemiologic [40] data demonstrated that the central nervous system is one of the targets of polychlorinated biphenyls (PCBs). The early or midlife brain intake of PCBs worsens nervous tissue aging, with an augmented risk of neurodegenerative disease [41]. Furthermore, exposure to these chemicals has been shown to increase risk based on age, causing adverse reproductive outcomes that may be related to exposure to POPs, and consequently altering oxidative stress markers [42,43]. Although regulated pesticide levels seem to be decreasing, there have been traces of DDT and other chlorinated compounds in recent studies conducted in Italy and Spain. Unfortunately, there is an obvious difficulty in comparing the variations in exposure in various countries because the studies refer to the total concentrations of the chlorinated substance in the food product rather than in the fat or liver of animals or fish.
On the other hand, vegetarian food could be a source of antioxidant molecules, serving as nutraceuticals. In fact, the abovementioned pesticides have been banned from most industrialised countries. Only food originating from remote areas could be a source of chlorination. In contrast, some substances present in food can help to counteract the damage caused by chlorinated chemicals, modulating the immune system and inhibiting the action of oxidative stress. Food and physical exercise demonstrated their potential in ameliorating oxidative stress status. Only few data were reported about gender differences in ROS production response. Mattioli et al. focused on these differences, noticing a diversity in food intake response between women and men [44]. One of the most promising nutrients in terms of its antioxidant capacity is resveratrol [41,45]. Moreover, substances extracted from plant material, such as fruit rich in anthocyanins, flavonoids and total polyphenols [46]; oil [47]; and chicken meat reformulated by the partial replacement of meat by Mediterranean plant ingredients [48], have been proven to have antioxidant qualities and health benefits. We have listed some of the foods acting as nutraceuticals with the molecules cited above (Table 2).

5. Conclusions

Most of the data obtained by several authors independently demonstrate that the trend in 3-ClTyr concentration in age-related disease and in inflammatory conditions is elevated. As mentioned above, ROSs are a paradigm of inflammation, which is the main characteristic of aging. For this reason, the term “inflammaging” was elaborated. Reaching old age is determined mainly by successful aging, which is typical of subjects with specific characteristics together with a favourable lifestyle. In a previous study [51] and in this paper, we reported that chlorinative stress is present in many diseases typical of the elderly. We also reported how diet could negatively or positively influence chlorinative stress, building the basis for a comparison of 3-ClTyr levels in the oldest old vs. youngest old, both with age-related disease and in healthy controls. Comparing the data between different geographic areas and countries could also give a scenario about the influence of pesticides in such results.

Author Contributions

Conceptualisation, S.G. and N.C.; methodology, M.C.; formal analysis, M.C. and E.D.S.; investigation, M.C., E.D.S. and C.M.G.; resources, S.G. and N.C.; data curation, C.M.G.; writing—original draft preparation, M.C. and E.D.S.; writing—review and editing, E.D.S. and C.M.G.; visualisation, M.C.; supervision, S.G and N.C.; project administration, S.G.; funding acquisition, N.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Newsholme, P.; Cruzat, V.F.; Keane, K.N.; Carlessi, R.; de Bittencourt, P.I.H., Jr. Molecular Mechanisms of ROS Production and Oxidative Stress in Diabetes. Biochem. J. 2016, 473, 4527–4550. [Google Scholar] [CrossRef] [PubMed]
  2. Langen, R.C.J.; Korn, S.H.; Wouters, E.F.M. ROS in the Local and Systemic Pathogenesis of COPD. Free Radic. Biol. Med. 2003, 35, 226–235. [Google Scholar] [CrossRef] [PubMed]
  3. Di Dalmazi, G.; Hirshberg, J.; Lyle, D.; Freij, J.B.; Caturegli, P. Reactive Oxygen Species in Organ-Specific Autoimmunity. Autoimmun. Highlights 2016, 7, 11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Furtmüller, P.G.; Burner, U.; Obinger, C. Reaction of Myeloperoxidase Compound I with Chloride, Bromide, Iodide, and Thiocyanate. Biochemistry 1998, 37, 17923–17930. [Google Scholar] [CrossRef] [PubMed]
  5. Davies, M.J. Myeloperoxidase-Derived Oxidation: Mechanisms of Biological Damage and Its Prevention. J. Clin. Biochem. Nutr. 2011, 48, 8–19. [Google Scholar] [CrossRef] [Green Version]
  6. Andrés, C.M.C.; Pérez de la Lastra, J.M.; Juan, C.A.; Plou, F.J.; Pérez-Lebeña, E. Hypochlorous Acid Chemistry in Mammalian Cells-Influence on Infection and Role in Various Pathologies. Int. J. Mol. Sci. 2022, 23, 10735. [Google Scholar] [CrossRef]
  7. Trivedi, M.V.; Laurence, J.S.; Siahaan, T.J. The Role of Thiols and Disulfides in Protein Chemical and Physical Stability. Curr. Protein Pept. Sci. 2009, 10, 614–625. [Google Scholar] [CrossRef] [Green Version]
  8. Luo, S.; Levine, R.L. Methionine in Proteins Defends against Oxidative Stress. FASEB J. 2009, 23, 464–472. [Google Scholar] [CrossRef] [Green Version]
  9. Pattison, D.I.; Davies, M.J. Absolute Rate Constants for the Reaction of Hypochlorous Acid with Protein Side Chains and Peptide Bonds. Chem. Res. Toxicol. 2001, 14, 1453–1464. [Google Scholar] [CrossRef]
  10. Pattison, D.I.; Davies, M.J. Reactions of Myeloperoxidase-Derived Oxidants with Biological Substrates: Gaining Chemical Insight into Human Inflammatory Diseases. Curr. Med. Chem. 2006, 13, 3271–3290. [Google Scholar] [CrossRef]
  11. Pattison, D.I.; Hawkins, C.L.; Davies, M.J. Hypochlorous Acid-Mediated Oxidation of Lipid Components and Antioxidants Present in Low-Density Lipoproteins: Absolute Rate Constants, Product Analysis, and Computational Modeling. Chem. Res. Toxicol. 2003, 16, 439–449. [Google Scholar] [CrossRef] [PubMed]
  12. Ramachandra, C.J.A.; Ja, K.P.M.M.; Chua, J.; Cong, S.; Shim, W.; Hausenloy, D.J. Myeloperoxidase As a Multifaceted Target for Cardiovascular Protection. Antioxid. Redox Signal. 2020, 32, 1135–1149. [Google Scholar] [CrossRef] [PubMed]
  13. Syslová, K.; Böhmová, A.; Mikoška, M.; Kuzma, M.; Pelclová, D.; Kačer, P. Multimarker Screening of Oxidative Stress in Aging. Oxid. Med. Cell Longev. 2014, 2014, 562860. [Google Scholar] [CrossRef] [Green Version]
  14. Peña-Bautista, C.; Tirle, T.; López-Nogueroles, M.; Vento, M.; Baquero, M.; Cháfer-Pericás, C. Oxidative Damage of DNA as Early Marker of Alzheimer’s Disease. Int. J. Mol. Sci. 2019, 20, 6136. [Google Scholar] [CrossRef] [Green Version]
  15. García-Moreno, J.-M.; Martín de Pablos, A.; García-Sánchez, M.-I.; Méndez-Lucena, C.; Damas-Hermoso, F.; Rus, M.; Chacón, J.; Fernández, E. May Serum Levels of Advanced Oxidized Protein Products Serve as a Prognostic Marker of Disease Duration in Patients with Idiopathic Parkinson’s Disease? Antioxid Redox Signal 2013, 18, 1296–1302. [Google Scholar] [CrossRef]
  16. O’Donnell, C.; Newbold, P.; White, P.; Thong, B.; Stone, H.; Stockley, R.A. 3-Chlorotyrosine in Sputum of COPD Patients: Relationship with Airway Inflammation. COPD: J. Chronic Obstr. Pulm. Dis. 2010, 7, 411–417. [Google Scholar] [CrossRef] [PubMed]
  17. Afshinnia, F.; Zeng, L.; Byun, J.; Gadegbeku, C.A.; Magnone, M.C.; Whatling, C.; Valastro, B.; Kretzler, M.; Pennathur, S. Myeloperoxidase Levels and Its Product 3-Chlorotyrosine Predict Chronic Kidney Disease Severity and Associated Coronary Artery Disease. Am. J. Nephrol. 2017, 46, 73–81. [Google Scholar] [CrossRef]
  18. Delporte, C.; Franck, T.; Noyon, C.; Dufour, D.; Rousseau, A.; Madhoun, P.; Desmet, J.-M.; Serteyn, D.; Raes, M.; Nortier, J.; et al. Simultaneous Measurement of Protein-Bound 3-Chlorotyrosine and Homocitrulline by LC–MS/MS after Hydrolysis Assisted by Microwave: Application to the Study of Myeloperoxidase Activity during Hemodialysis. Talanta 2012, 99, 603–609. [Google Scholar] [CrossRef]
  19. Cheng, M.-L.; Chen, C.-M.; Gu, P.-W.; Ho, H.-Y.; Chiu, D.T.-Y. Elevated Levels of Myeloperoxidase, White Blood Cell Count and 3-Chlorotyrosine in Taiwanese Patients with Acute Myocardial Infarction. Clin. Biochem. 2008, 41, 554–560. [Google Scholar] [CrossRef]
  20. Wang, G.; Mathew, A.V.; Yu, H.; Li, L.; He, L.; Gao, W.; Liu, X.; Guo, Y.; Byun, J.; Zhang, J.; et al. Myeloperoxidase Mediated HDL Oxidation and HDL Proteome Changes Do Not Contribute to Dysfunctional HDL in Chinese Subjects with Coronary Artery Disease. PLoS ONE 2018, 13, e0193782. [Google Scholar] [CrossRef]
  21. Mocatta, T.J.; Pilbrow, A.P.; Cameron, V.A.; Senthilmohan, R.; Frampton, C.M.; Richards, A.M.; Winterbourn, C.C. Plasma Concentrations of Myeloperoxidase Predict Mortality after Myocardial Infarction. J. Am. Coll. Cardiol. 2007, 49, 1993–2000. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  22. Shao, B.; Tang, C.; Sinha, A.; Mayer, P.S.; Davenport, G.D.; Brot, N.; Oda, M.N.; Zhao, X.-Q.; Heinecke, J.W. Humans with Atherosclerosis Have Impaired ABCA1 Cholesterol Efflux and Enhanced HDL Oxidation by Myeloperoxidase. Circ. Res. 2014, 114, 1733–1742. [Google Scholar] [CrossRef]
  23. Fleszar, M.G.; Fortuna, P.; Zawadzki, M.; Kosyk, B.; Krzystek-Korpacka, M. Simultaneous LC-MS/MS-Based Quantification of Free 3-Nitro-l-Tyrosine, 3-Chloro-l-Tyrosine, and 3-Bromo-l-Tyrosine in Plasma of Colorectal Cancer Patients during Early Postoperative Period. Molecules 2020, 25, 5158. [Google Scholar] [CrossRef]
  24. Stamp, L.K.; Khalilova, I.; Tarr, J.M.; Senthilmohan, R.; Turner, R.; Haigh, R.C.; Winyard, P.G.; Kettle, A.J. Myeloperoxidase and Oxidative Stress in Rheumatoid Arthritis. Rheumatology 2012, 51, 1796–1803. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  25. Vivekanandan-Giri, A.; Slocum, J.L.; Byun, J.; Tang, C.; Sands, R.L.; Gillespie, B.W.; Heinecke, J.W.; Saran, R.; Kaplan, M.J.; Pennathur, S. High Density Lipoprotein Is Targeted for Oxidation by Myeloperoxidase in Rheumatoid Arthritis. Ann. Rheum. Dis. 2013, 72, 1725. [Google Scholar] [CrossRef] [PubMed]
  26. Higashi, N.; Mita, H.; Taniguchi, M.; Turikisawa, N.; Higashi, A.; Ozawa, Y.; Tohma, S.; Arimura, K.; Akiyama, K. Urinary Eicosanoid and Tyrosine Derivative Concentrations in Patients with Vasculitides. J. Allergy Clin. Immunol. 2004, 114, 1353–1358. [Google Scholar] [CrossRef] [PubMed]
  27. Kato, Y.; Maruyama, W.; Naoi, M.; Hashizume, Y.; Osawa, T. Immunohistochemical Detection of Dityrosine in Lipofuscin Pigments in the Aged Human Brain. FEBS Lett. 1998, 439, 231–234. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  28. Sharma, R.N.; Goel, S. Chlorinated Drinking Water, Cancers and Adverse Health Outcomes in Gangtok, Sikkim, India. J. Env. Sci. Eng. 2007, 49, 247–254. [Google Scholar]
  29. Cook, N.L.; Viola, H.M.; Sharov, V.S.; Hool, L.C.; Schöneich, C.; Davies, M.J. Myeloperoxidase-Derived Oxidants Inhibit Sarco/Endoplasmic Reticulum Ca2+-ATPase Activity, and Perturb Ca2+ Homeostasis in Human Coronary Artery Endothelial Cells. Free Radic. Biol. Med. 2012, 52, 951–961. [Google Scholar] [CrossRef] [Green Version]
  30. Ray, R.S.; Katyal, A. Myeloperoxidase: Bridging the Gap in Neurodegeneration. Neurosci. Biobehav. Rev. 2016, 68, 611–620. [Google Scholar] [CrossRef]
  31. Cabassi, A.; Binno, S.M.; Tedeschi, S.; Graiani, G.; Galizia, C.; Bianconcini, M.; Coghi, P.; Fellini, F.; Ruffini, L.; Govoni, P.; et al. Myeloperoxidase-Related Chlorination Activity Is Positively Associated with Circulating Ceruloplasmin in Chronic Heart Failure Patients: Relationship with Neurohormonal, Inflammatory, and Nutritional Parameters. Biomed. Res. Int. 2015, 2015, 691693. [Google Scholar] [CrossRef] [PubMed]
  32. Davalli, P.; Mitic, T.; Caporali, A.; Lauriola, A.; D’Arca, D. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases. Oxidative Med. Cell. Longev. 2016, 2016, 3565127. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. Giorgi, C.; Marchi, S.; Simoes, I.C.; Ren, Z.; Morciano, G.; Perrone, M.; Patalas-Krawczyk, P.; Borchard, S.; Jędrak, P.; Pierzynowska, K. Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases. Int. Rev. Cell Mol. Biol. 2018, 340, 209–344. [Google Scholar]
  34. Gangemi, S.; Basile, G.; Merendino, R.A.; Minciullo, P.L.; Novick, D.; Rubinstein, M.; Dinarello, C.A.; Balbo, C.L.; Franceschi, C.; Basili, S.; et al. Increased Circulating Interleukin-18 Levels in Centenarians with No Signs of Vascular Disease: Another Paradox of Longevity? Exp. Gerontol. 2003, 38, 669–672. [Google Scholar] [CrossRef] [PubMed]
  35. Regulation (EC) No 850/2004 of the European Parliament and of the Council of 29 April 2004 on Persistent Organic Pollutants and Amending Directive 79/117/EEC. 2004, Volume 158. Available online: https://eur-lex.europa.eu (accessed on 16 November 2022).
  36. Fontcuberta, M.; Arqués, J.F.; Villalbí, J.R.; Martínez, M.; Centrich, F.; Serrahima, E.; Pineda, L.; Duran, J.; Casas, C. Chlorinated Organic Pesticides in Marketed Food: Barcelona, 2001–2006. Sci. Total Environ. 2008, 389, 52–57. [Google Scholar] [CrossRef]
  37. Dueri, S.; Castro-Jiménez, J.; Comenges, J.-M.Z. On the Use of the Partitioning Approach to Derive Environmental Quality Standards (EQS) for Persistent Organic Pollutants (POPs) in Sediments: A Review of Existing Data. Sci. Total Environ. 2008, 403, 23–33. [Google Scholar] [CrossRef]
  38. Cerrillo, I.; Olea-Serrano, M.F.; Ibarluzea, J.; Exposito, J.; Torne, P.; Laguna, J.; Pedraza, V.; Olea, N. Environmental and Lifestyle Factors for Organochlorine Exposure among Women Living in Southern Spain. Chemosphere 2006, 62, 1917–1924. [Google Scholar] [CrossRef]
  39. Lopez-Espinosa, M.-J.; Granada, A.; Carreno, J.; Salvatierra, M.; Olea-Serrano, F.; Olea, N. Organochlorine Pesticides in Placentas from Southern Spain and Some Related Factors. Placenta 2007, 28, 631–638. [Google Scholar] [CrossRef]
  40. Berghuis, S.A.; Bos, A.F.; Sauer, P.J.J.; Roze, E. Developmental Neurotoxicity of Persistent Organic Pollutants: An Update on Childhood Outcome. Arch. Toxicol. 2015, 89, 687–709. [Google Scholar] [CrossRef]
  41. Fumia, A.; Cicero, N.; Gitto, M.; Nicosia, N.; Alesci, A. Role of Nutraceuticals on Neurodegenerative Diseases: Neuroprotective and Immunomodulant Activity. Nat. Prod. Res. 2021, 36, 1–18. [Google Scholar] [CrossRef]
  42. Björvang, R.D.; Hallberg, I.; Pikki, A.; Berglund, L.; Pedrelli, M.; Kiviranta, H.; Rantakokko, P.; Ruokojärvi, P.; Lindh, C.H.; Olovsson, M.; et al. Follicular Fluid and Blood Levels of Persistent Organic Pollutants and Reproductive Outcomes among Women Undergoing Assisted Reproductive Technologies. Environ. Res. 2022, 208, 112626. [Google Scholar] [CrossRef] [PubMed]
  43. Lee, S.; Ko, E.; Lee, H.; Kim, K.-T.; Choi, M.; Shin, S. Mixed Exposure of Persistent Organic Pollutants Alters Oxidative Stress Markers and Mitochondrial Function in the Tail of Zebrafish Depending on Sex. Int. J. Environ. Res. Public Health 2021, 18, 9539. [Google Scholar] [CrossRef] [PubMed]
  44. Mattioli, A.V.; Selleri, V.; Zanini, G.; Nasi, M.; Pinti, M.; Stefanelli, C.; Fedele, F.; Gallina, S. Physical Activity and Diet in Older Women: A Narrative Review. J. Clin. Med. 2023, 12, 81. [Google Scholar] [CrossRef] [PubMed]
  45. Alesci, A.; Nicosia, N.; Fumia, A.; Giorgianni, F.; Santini, A.; Cicero, N. Resveratrol and Immune Cells: A Link to Improve Human Health. Molecules 2022, 27, 424. [Google Scholar] [CrossRef] [PubMed]
  46. Gervasi, T.; Oliveri, F.; Gottuso, V.; Squadrito, M.; Bartolomeo, G.; Cicero, N.; Dugo, G. Nero d’Avola and Perricone Cultivars: Determination of Polyphenols, Flavonoids and Anthocyanins in Grapes and Wines. Nat. Prod. Res. 2016, 30, 2329–2337. [Google Scholar] [CrossRef]
  47. Fejér, J.; Kron, I.; Pellizzeri, V.; Pľuchtová, M.; Eliašová, A.; Campone, L.; Gervasi, T.; Bartolomeo, G.; Cicero, N.; Babejová, A.; et al. First Report on Evaluation of Basic Nutritional and Antioxidant Properties of Moringa Oleifera Lam. from Caribbean Island of Saint Lucia. Plants 2019, 8, 537. [Google Scholar] [CrossRef] [Green Version]
  48. Albergamo, A.; Vadalà, R.; Metro, D.; Nava, V.; Bartolomeo, G.; Rando, R.; Macrì, A.; Messina, L.; Gualtieri, R.; Colombo, N.; et al. Physicochemical, Nutritional, Microbiological, and Sensory Qualities of Chicken Burgers Reformulated with Mediterranean Plant Ingredients and Health-Promoting Compounds. Foods 2021, 10, 2129. [Google Scholar] [CrossRef]
  49. Fang, J. Classification of Fruits Based on Anthocyanin Types and Relevance to Their Health Effects. Nutrition 2015, 31, 1301–1306. [Google Scholar] [CrossRef]
  50. Reboredo-Rodríguez, P.; Varela-López, A.; Forbes-Hernández, T.Y.; Gasparrini, M.; Afrin, S.; Cianciosi, D.; Zhang, J.; Manna, P.P.; Bompadre, S.; Quiles, J.L.; et al. Phenolic Compounds Isolated from Olive Oil as Nutraceutical Tools for the Prevention and Management of Cancer and Cardiovascular Diseases. Int. J. Mol. Sci. 2018, 19, 2305. [Google Scholar] [CrossRef] [Green Version]
  51. Casciaro, M.; Di Salvo, E.; Pace, E.; Ventura-Spagnolo, E.; Navarra, M.; Gangemi, S. Chlorinative Stress in Age-Related Diseases: A Literature Review. Immun. Ageing 2017, 14, 1–7. [Google Scholar] [CrossRef]
Antioxidants 12 00249 g001 550
Figure 1. Hypochlorus acid production starts from MPO interactions with hydrogen peroxide.
Figure 1. Hypochlorus acid production starts from MPO interactions with hydrogen peroxide.
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Antioxidants 12 00249 g002 550
Figure 2. Hypochlorous acid is formed from hydrogen peroxide and chloride anion by MPO as a catalyst. MPO catalyses the transformation of hydrogen peroxide (H2O2) and chloride anion (Cl−) into highly reactive hypochlorous acid. 3-ClTyr is a product resulting from the combination of HOCl and p-tyrosine.
Figure 2. Hypochlorous acid is formed from hydrogen peroxide and chloride anion by MPO as a catalyst. MPO catalyses the transformation of hydrogen peroxide (H2O2) and chloride anion (Cl−) into highly reactive hypochlorous acid. 3-ClTyr is a product resulting from the combination of HOCl and p-tyrosine.
Antioxidants 12 00249 g002
Table
Table 1. A list of the research articles included in the review evaluating chlorinative stress in elderly patients.
Table 1. A list of the research articles included in the review evaluating chlorinative stress in elderly patients.
ReferenceN° of PatientsMean AgeTissueDisease3-ClTyr
[14]5370UrineAlzheimer’s diseaseNormal
[15]6063Serum; Cerebrospinal fluidParkinson’s diseasen.d.
[16]1465SputumCOPD+
[17]2367SerumKidney failure+
[18]1577SerumKidney failure+
[19]7765SerumAcute myocardial infarction+
[20]2063SerumCoronary diseaseNormal
[21]51262SerumMyocardial infarctionNormal
[22]2064SerumStable coronary disease+
[22]2063SerumAcute coronary syndrome+
[23]7566SerumColorectal cancer+
[24]7782SerumRheumatoid arthritis+
[25]3863SerumRheumatoid arthritis+
[26]866UrineVasculitis+
[27]369BrainAneurism; myocardial infarction; lung cancer+
Table
Table 2. Examples of foods rich in polyphenols helpful in reducing oxidative stress, typical of the Mediterranean diet.
Table 2. Examples of foods rich in polyphenols helpful in reducing oxidative stress, typical of the Mediterranean diet.
Foods Rich in Polyphenols [49,50]
Strawberries
Raspberries
Cherries
Blueberries
Grapes
Mulberries
Olive oil
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Di Salvo, E.; Casciaro, M.; Giorgianni, C.M.; Cicero, N.; Gangemi, S. Age-Related Diseases and Foods Generating Chlorinative Stress. Antioxidants 2023, 12, 249. https://doi.org/10.3390/antiox12020249

AMA Style

Di Salvo E, Casciaro M, Giorgianni CM, Cicero N, Gangemi S. Age-Related Diseases and Foods Generating Chlorinative Stress. Antioxidants. 2023; 12(2):249. https://doi.org/10.3390/antiox12020249

Chicago/Turabian Style

Di Salvo, Eleonora, Marco Casciaro, Concetto Mario Giorgianni, Nicola Cicero, and Sebastiano Gangemi. 2023. "Age-Related Diseases and Foods Generating Chlorinative Stress" Antioxidants 12, no. 2: 249. https://doi.org/10.3390/antiox12020249

APA Style

Di Salvo, E., Casciaro, M., Giorgianni, C. M., Cicero, N., & Gangemi, S. (2023). Age-Related Diseases and Foods Generating Chlorinative Stress. Antioxidants, 12(2), 249. https://doi.org/10.3390/antiox12020249

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