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Veterinary Drugs—2nd Edition

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 11927

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Prof. Dr. Mihai Cosmin Cenariu

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Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania
Interests: livestock health and management; drug design and development; nanomedicine; flow cytometry; molecular biology
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Prof. Dr. Sanda Andrei

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Department of Preclinical Sciences, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania
Interests: oxidative stress; in vitro and in vivo antioxidant activity; antioxidant enzymes; natural antioxidants
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Prof. Dr. Adela Pintea

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Department Biochemistry, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj Napoca, 400372 Cluj Napoca, Romania
Interests: natural antioxidants; oxidative stress; reactive oxygen species; in vitro antioxidant tests; lipophilic compounds; chromatograph
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Dear Colleagues,

Treating diseases with medicinal substances has been attempted since ancestral times, initially in a primitive and empiric way, but gradually developing into a well-defined science, with strict norms and very clear protocols. Up until recently, veterinary drugs were developed together with human drugs, without clear differentiation between the two. Nevertheless, in recent decades, a clear distinction between drugs intended for human and animal use has been made, although some molecules are still used in both branches of medicine.

Veterinary drugs are substances that are administered to animals in order to prevent or treat a certain disease, to facilitate a certain diagnosis, or to modify various normal behaviors (tranquilizers) or functions (estrus synchronization, ovulation, increase in growth rate, improved milk production, or chemical castration).

The strict regulations that apply to human drug production can be found in the veterinary pharmaceutical industry as well, with very well-established quality control keys and thorough standard operating procedures that ensure the high-quality standard of the end product. Some of those guidelines imply that veterinary drugs must first and foremost be as harmless as possible to the animal patient but at the same time be effective in treating the targeted disease. Moreover, drugs intended for use in food-producing animals must also not pose a risk for human consumers of products derived from treated animals.

In order to prove the high quality of a veterinary drug (as demonstrated by its efficacy and safety), a certain molecule must go through a challenging process of validation, which involves top-quality scientific research and thorough testing. Thus, this Special Issue welcomes original research and reviews of the literature that refer to:

Pharmacology and pharmacokinetics of veterinary drugs;
Toxicology studies on veterinary drugs;
Testing of various molecules for veterinary use;
Food safety and analytical chemistry of all classes of drugs used in veterinary medicine.

Prof. Dr. Mihai Cosmin Cenariu
Prof. Dr. Sanda Andrei
Prof. Dr. Adela Pintea
Guest Editors

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Keywords

veterinary drugs
veterinary pharmacology and pharmacokinetics
veterinary drug toxicology
food safety
analytical chemistry

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Related Special Issue

Veterinary Drugs in Molecules (12 articles)

Published Papers (8 papers)

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Research

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17 pages, 2054 KiB

Open AccessFeature PaperArticle

A Zebrafish Embryo Model to Screen Potential Therapeutic Compounds in Sapindaceae Poisoning

by Clovis P. Wouters, Benjamin Klein, Nicholas Price, François Boemer, Marianne L. Voz and Dominique-Marie Votion

Molecules 2024, 29(20), 4954; https://doi.org/10.3390/molecules29204954 - 19 Oct 2024

Viewed by 663

Abstract

Hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG) are protoxins produced by Sapindaceae plants, particularly Acer pseudoplatanus, and are responsible for causing atypical myopathy (AM) in equids. These protoxins metabolise into toxic compounds, such as methylenecyclopropylacetyl-CoA (MCPA-CoA), which alters energy metabolism and induces severe rhabdomyolysis. Currently, no specific treatment exists for this poisoning, in vitro models fail to reproduce HGA’s toxic effects on equine primary myoblasts, and mammalian models are impractical for large-scale drug screening. This study aimed to develop a zebrafish embryo model for screening therapeutic compounds against AM. Zebrafish embryos were exposed to various concentrations of HGA, MCPrG, and methylenecyclopropylacetate (MCPA) for 72 h. MCPrG did not induce toxicity, while HGA and MCPA showed median lethal concentration (LC50) values of 1.7 µM and 1 µM after 72 h, respectively. The highest levels of the conjugated metabolite MCPA–carnitine were detected 24 h after HGA exposure, and the acylcarnitines profile was highly increased 48 h post-exposure. Isovaleryl-/2- methylbutyrylcarnitine levels notably rose after 24 h, suggesting potential exposition biomarkers. Glycine and carnitine effectively reduced mortality, whereas riboflavin showed no protective effect. These findings suggest that the zebrafish embryo represents a valuable model for identifying therapeutic compounds for Sapindaceae poisoning. Full article

(This article belongs to the Special Issue Veterinary Drugs—2nd Edition)

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16 pages, 4702 KiB

Open AccessArticle

Inclusion Complexes of Ethanamizuril with β- and Hydroxypropyl-β-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study

by Juan Guo, Lifang Zhang, Mi Wang, Yingchun Liu and Chenzhong Fei

Molecules 2024, 29(10), 2164; https://doi.org/10.3390/molecules29102164 - 7 May 2024

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Abstract

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, ¹H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher K_f (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL. Full article

(This article belongs to the Special Issue Veterinary Drugs—2nd Edition)

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21 pages, 5231 KiB

Open AccessArticle

Randomly Methylated β-Cyclodextrin Inclusion Complex with Ketoconazole: Preparation, Characterization, and Improvement of Pharmacological Profiles

by Yili Ding, Shufeng Xu, Charles Ding, Zhiyuan Zhang and Zhe Xu

Molecules 2024, 29(9), 1915; https://doi.org/10.3390/molecules29091915 - 23 Apr 2024

Cited by 1 | Viewed by 1067

Abstract

As a powerful imidazole antifungal drug, ketoconazole’s low solubility (0.017 mg/mL), together with its odor and irritation, limited its clinical applications. The inclusion complex of ketoconazole with randomly methylated β-cyclodextrin was prepared by using an aqueous solution method after cyclodextrin selection through phase solubility studies, complexation methods, and condition selection through single factor and orthogonal strategies. The complex was confirmed by FTIR (Fourier-transform infrared spectroscopy), DSC (differential scanning calorimetry), TGA (thermogravimetric analysis), SEM (scanning electron microscope images), and NMR (Nuclear magnetic resonance) studies. Through complexation, the water solubility of ketoconazole in the complex was increased 17,000 times compared with that of ketoconazole alone, which is the best result so far for the ketoconazole water solubility study. In in vitro pharmacokinetic studies, ketoconazole in the complex can be 100% released in 75 min, and in in vivo pharmacokinetic studies in dogs, through the complexation, the C_max was increased from 7.56 μg/mL to 13.58 µg/mL, and the AUC_0~72 was increased from 22.69 μgh/mL to 50.19 μgh/mL, indicating that this ketoconazole complex can be used as a more efficient potential new anti-fungal drug. Full article

(This article belongs to the Special Issue Veterinary Drugs—2nd Edition)

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23 pages, 8032 KiB

Open AccessArticle

Optimization of Ethanol Extraction Technology for Yujin Powder Using Response Surface Methodology with a Box–Behnken Design Based on Analytic Hierarchy Process–Criteria Importance through Intercriteria Correlation Weight Analysis and Its Safety Evaluation

by Lidong Jiang, Wangdong Zhang, Wenbo Zhao, Yanzi Cai, Xue Qin, Baoshan Wang, Jiao Xue, Yanqiao Wen, Yanming Wei, Yongli Hua and Wanling Yao

Molecules 2023, 28(24), 8124; https://doi.org/10.3390/molecules28248124 - 15 Dec 2023

Viewed by 1179

Abstract

Here, we aimed to optimize the ethanol extraction technology for Yujin powder (YJP) and evaluate its safety. The ultrasonic-assisted ethanol reflux extraction method refluxing was used to extract YJP. The parameters were optimized through a combination of single-factor and response surface methodology (RSM). The comprehensive Y value score calculated using the content of 13 active ingredients in YJP ethanolic extracts (YEEs) and the yield of the dry extract were used as measuring criteria. RSM with a Box–Behnken design using three factors and three levels was adopted to optimize the ethanol extraction technology for YJP. Finally, acute and subchronic toxicity tests were performed to evaluate its safety. The results revealed the best technological parameters: a liquid–material ratio of 24:1, an ethanol concentration of 69%, assistance of ultrasound (40 °C, 50 kHZ, 30 min), reflux time of 53 min, and reflux temperature of 50 °C. In acute toxicity tests, the maximum administration dosage in mice was 28.21 g/kg, which is higher than 10 times the clinical dosage. Adverse effects in the acute and subchronic toxicity tests were not observed. All clinical indexes were normal. In conclusion, the RSM based on AHP–CRITIC weight analysis could be used to optimize the ethanol extraction technology for YJP and YEEs prepared under the above conditions and ensure high safety. Full article

(This article belongs to the Special Issue Veterinary Drugs—2nd Edition)

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14 pages, 16910 KiB

Open AccessArticle

Protopine Alleviates Dextran Sodium Sulfate-Induced Ulcerative Colitis by Improving Intestinal Barrier Function and Regulating Intestinal Microbiota

by Meishan Yue, Jialu Huang, Xiaolan Ma, Peng Huang, Yisong Liu and Jianguo Zeng

Molecules 2023, 28(13), 5277; https://doi.org/10.3390/molecules28135277 - 7 Jul 2023

Cited by 8 | Viewed by 1946

Abstract

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), and its pathogenesis is related to intestinal mucosal barrier damage and gut microbiota imbalance. Protopine (PRO), an isoquinoline alkaloid, is one of the main anti-inflammatory ingredients of traditional Chinese medicine Macleaya cordata (Willd.) R. Br. This study investigated the effects of PRO on the intestinal mucosal barrier and gut microbiota in dextran sodium sulfate (DSS)-induced colitis mice. C57BL/6J mice were treated with 3% DSS in drinking water to induce acute colitis, while PRO was administered orally once daily for 7 days. The results showed that PRO administration significantly alleviated the symptoms of DSS-induced colitis in mice and inhibited the expression of inflammation-related genes. In addition, PRO restored the integrity of the intestinal barrier in colitis mice by restoring colonic mucin secretion and promoting the expression of tight junction proteins. Furthermore, PRO alleviated the DSS-induced gut microbiota dysbiosis by decreasing the abundance of Proteobacteria, Escherichia-Shigella and Enterococcus, as well as enhancing the abundance of beneficial bacteria, such as Firmicutes and Akkermansia. These findings suggested that PRO effectively alleviated DSS-induced ulcerative colitis by suppressing the expression of inflammation-related genes, maintaining the intestinal mucosal barrier and regulating the intestinal microbiota. Full article

(This article belongs to the Special Issue Veterinary Drugs—2nd Edition)

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17 pages, 1811 KiB

Open AccessArticle

Enhanced Bioactive Potential of Functionalized Injectable Platelet-Rich Plasma

by Emoke Pall, Alexandra Roman, Diana Olah, Florin Ioan Beteg, Mihai Cenariu and Marina Spînu

Molecules 2023, 28(4), 1943; https://doi.org/10.3390/molecules28041943 - 17 Feb 2023

Cited by 6 | Viewed by 1848

Abstract

Injectable platelet-rich fibrin (iPRF) is a frequently used platelet concentrate used for various medical purposes both in veterinary and human medicine due to the regenerative potential of hard and soft tissues, and also because of its antimicrobial effectiveness. This in vitro study was carried out to assess the cumulative antimicrobial and antibiofilm effect of iPRF functionalized with a multifunctional glycoprotein, human lactoferrin (Lf). Thus, the ability to potentiate cell proliferation was tested on keratinocytes and evaluated by the CCK8 test. The combinations of iPRF and Lf induced an increase in the proliferation rate after 24 h. The average cell viability of treated cultures (all nine variants) was 102.87% ± 1.00, and the growth tendency was maintained even at 48 h. The highest proliferation rate was observed in cultures treated with 7% iPRF in combination with 50 µg/mL of Lf, with an average viability of 102.40% ± 0.80. The antibacterial and antibiofilm activity of iPRF, of human lactoferrin and their combination were tested by agar-well diffusion (Kirby–Bauer assay), broth microdilution, and crystal violet assay against five reference bacterial strains. iPRF showed antimicrobial and antibiofilm potential, but with variations depending on the tested bacterial strain. The global analysis of the results indicates an increased antimicrobial potential at the highest concentration of Lf mixed with iPRF. The study findings confirmed the hypothesized enhanced bioactive properties of functionalized iPRF against both Gram-positive and Gram-negative biofilm-producing bacteria. These findings could be further applied, but additional studies are needed to evaluate the mechanisms that are involved in these specific bioactive properties. Full article

(This article belongs to the Special Issue Veterinary Drugs—2nd Edition)

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Review

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32 pages, 470 KiB

Open AccessReview

Some Aspects and Convergence of Human and Veterinary Drug Repositioning

by Patrik Mag, Melinda Nemes-Terényi, Ákos Jerzsele and Péter Mátyus

Molecules 2024, 29(18), 4475; https://doi.org/10.3390/molecules29184475 - 20 Sep 2024

Viewed by 1453

Abstract

Drug innovation traditionally follows a de novo approach with new molecules through a complex preclinical and clinical pathway. In addition to this strategy, drug repositioning has also become an important complementary approach, which can be shorter, cheaper, and less risky. This review provides an overview of drug innovation in both human and veterinary medicine, with a focus on drug repositioning. The evolution of drug repositioning and the effectiveness of this approach are presented, including the growing role of data science and computational modeling methods in identifying drugs with potential for repositioning. Certain business aspects of drug innovation, especially the relevant factors of market exclusivity, are also discussed. Despite the promising potential of drug repositioning for innovation, it remains underutilized, especially in veterinary applications. To change this landscape for mutual benefits of human and veterinary drug innovation, further exploitation of the potency of drug repositioning is necessary through closer cooperation between all stakeholders, academia, industry, pharmaceutical authorities, and innovation policy makers, and the integration of human and veterinary repositioning into a unified innovation space. For this purpose, the establishment of the conceptually new “One Health Drug Repositioning Platform” is proposed. Oncology is one of the disease areas where this platform can significantly support the development of new drugs for human and dog (or other companion animals) anticancer therapies. As an example of the utilization of human and veterinary drugs for veterinary repositioning, the use of COX inhibitors to treat dog cancers is reviewed. Full article

(This article belongs to the Special Issue Veterinary Drugs—2nd Edition)

17 pages, 1327 KiB

Open AccessReview

Short Review on the Biological Activity of Cyclodextrin-Drug Inclusion Complexes Applicable in Veterinary Therapy

by Mariana Grecu, Bogdan Minea, Liliana-Georgeta Foia, Andra-Cristina Bostanaru-Iliescu, Liviu Miron, Valentin Nastasa and Mihai Mares

Molecules 2023, 28(14), 5565; https://doi.org/10.3390/molecules28145565 - 21 Jul 2023

Cited by 7 | Viewed by 1784

Abstract

Cyclodextrins (CDs) are a family of carrier molecules used to improve the pharmacokinetic parameters of therapeutic molecules. These cyclic oligosaccharides have medical and pharmaceutical applications by being able to form inclusion complexes with molecules that are poorly soluble in water. The benefits of these complexes are directed towards improving the chemical and biological properties—i.e., solubility, bioavailability, stability, non-toxicity and shelf life of drug molecules. Since the 1960s, the first inclusion complexes used in therapeutics were those with α-, β- and γ-CD, which proved their usefulness, but had certain degrees of particularly renal toxicity. Currently, to correct these deficiencies, β-CD derivatives are most frequently used, such as sulfobutylether-β-CD, hydroxypropyl-β-CD, etc. Therefore, it is of interest to bring to the attention of those interested the diversity of current and potential future clinical applications of inclusion complexes in veterinary medicine and to present the contribution of these inclusion complexes in improving drug efficacy. The most important biological activities of β-CD complexed molecules in the veterinary field are summarized in this short review. Full article

(This article belongs to the Special Issue Veterinary Drugs—2nd Edition)

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