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Metabolites
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Toxic Effects and Metabolic Regulations of Hazardous Chemicals in Animal-Derived...
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Toxic Effects and Metabolic Regulations of Hazardous Chemicals in Animal-Derived Food

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Animal Metabolism".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 10205

Special Issue Editors

Prof. Dr. Chongshan Dai

E-Mail Website
Guest Editor
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China
Interests: antioxidants; oxidative stress; molecular mechanism; autophagy; ferroptosis; neurotoxicity
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Haiyang Jiang

E-Mail Website
Guest Editor
College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, China
Interests: toxic effects; cell death; molecular mechanism; veterinary residues; risk assessment

Special Issue Information

Dear Colleagues,

Animal-derived food is all edible animal products, including eggs and milk,  meat, and their products. Biological, chemical, and physical agents are three categories of safety hazards to animal-derived food safety. Chemical contaminants, including veterinary drugs, heavy metals, nanomaterials, environmental pollutants, feed additives, and natural toxins (such as mycotoxins and bacterial toxins) can occur in animal-derived food, and could cause various harmful effects to animals or humans, including hepatotoxicity, nephrotoxicity, reproductive toxicity, neurotoxicity, or cardiovascular toxicity. The toxic effects caused by chemical hazard contaminants are often complex and content-dependent. To develop the effective prevention and control strategies, understanding the precise molecular mechanisms of these chemical contaminants-caused toxic effects is required. It has reported that many chemical contaminants in the low dose could damage cellular DNA, lipids, and proteins, finally resulting in various serious toxic effects. Recent studies showed that some chemical hazard contaminants could induce metabolism-dependent cell death by affecting multiple metabolic pathways in cell autophagy and ferroptosis, including glycolysis, pentose phosphate pathway, hexosamine biosynthetic pathway, and tricarboxylic acid (TCA) cycle, These evidences reveal that metabolism regulations may play a critical role in chemical contaminants-induced toxic effects or cell death. In this Special Issue, we aim to collate innovative original research and review articles that reveal the toxic effects of chemical hazard contaminants, molecular mechanisms, and metabolic regulations by using in vitro and in vivo models.

Dr. Chongshan Dai
Prof. Dr. Haiyang Jiang
Guest Editors

Manuscript Submission Information

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Keywords

  • toxic effects
  • metabolic regulations
  • hazardous chemicals
  • animal-derived food safety
  • risk assessment
  • cell death
  • animal model 
  • in vitro model

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Published Papers (5 papers)

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Research

14 pages, 2350 KiB  
Article
Study on the Metabolic Transformation Rule of Enrofloxacin Combined with Tilmicosin in Laying Hens
by Jingchao Guo, Liyun Zhang, Yongxia Zhao, Awais Ihsan, Xu Wang and Yanfei Tao
Metabolites 2023, 13(4), 528; https://doi.org/10.3390/metabo13040528 - 6 Apr 2023
Cited by 1 | Viewed by 2165
Abstract
There is often abuse of drugs in livestock and poultry production, and the improper use of drugs leads to the existence of a low level of residues in eggs, which is a potential threat to human safety. Enrofloxacin (EF) and tilmicosin (TIM) are [...] Read more.
There is often abuse of drugs in livestock and poultry production, and the improper use of drugs leads to the existence of a low level of residues in eggs, which is a potential threat to human safety. Enrofloxacin (EF) and tilmicosin (TIM) are regularly combined for the prevention and treatment of poultry diseases. The current studies on EF or TIM mainly focus on a single drug, and the effects of the combined application of these two antibiotics on EF metabolism in laying hens are rarely reported. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the residual EF and TIM in laying hens and to investigate the effect of TIM on the EF metabolism in laying hens. In this paper, we first establish a method that can detect EF and TIM simultaneously. Secondly, the results showed that the highest concentration of EF in the egg samples was 974.92 ± 441.71 μg/kg on the 5th day of treatment. The highest concentration of EF in the egg samples of the combined administration group was 1256.41 ± 226.10 μg/kg on the 5th day of administration. The results showed that when EF and TIM were used in combination, the residue of EF in the eggs was increased, the elimination rate of EF was decreased, and the half-life of EF was increased. Therefore, the use of EF and TIM in combination should be treated with greater care and supervision should be strengthened to avoid risks to human health. Full article
(This article belongs to the Special Issue Toxic Effects and Metabolic Regulations of Hazardous Chemicals in Animal-Derived Food)
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13 pages, 3489 KiB  
Article
In Vitro Evaluation Reveals Effect and Mechanism of Artemether against Toxoplasma gondii
by Qiong Xu, Yin-Yan Duan, Ming Pan, Qi-Wang Jin, Jian-Ping Tao and Si-Yang Huang
Metabolites 2023, 13(4), 476; https://doi.org/10.3390/metabo13040476 - 27 Mar 2023
Cited by 2 | Viewed by 1794
Abstract
Due to the limited effectiveness of existing drugs for the treatment of toxoplasmosis, there is a dire need for the discovery of new therapeutic options. Artemether is an important drug for malaria and several studies have indicated that it also exhibits anti-T. [...] Read more.
Due to the limited effectiveness of existing drugs for the treatment of toxoplasmosis, there is a dire need for the discovery of new therapeutic options. Artemether is an important drug for malaria and several studies have indicated that it also exhibits anti-T. gondii activity. However, its specific effect and mechanisms are still not clear. To elucidate its specific role and potential mechanism, we first evaluated its cytotoxicity and anti-Toxoplasma effect on human foreskin fibroblast cells, and then analyzed its inhibitory activity during T. gondii invasion and intracellular proliferation. Finally, we examined its effect on mitochondrial membrane potential and reactive oxygen species (ROS) in T. gondii. The CC50 value of artemether was found to be 866.4 μM, and IC50 was 9.035 μM. It exhibited anti-T. gondii activity and inhibited the growth of T. gondii in a dose-dependent manner. We also found that the inhibition occurred primarily in intracellular proliferation, achieved by reducing the mitochondrial membrane integrity of T. gondii and stimulating ROS production. These findings suggest that the mechanism of artemether against T. gondii is related to a change in the mitochondrial membrane and the increase in ROS production, which may provide a theoretical basis for optimizing artemether derivatives and further improving their anti-Toxoplasma efficacy. Full article
(This article belongs to the Special Issue Toxic Effects and Metabolic Regulations of Hazardous Chemicals in Animal-Derived Food)
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18 pages, 4647 KiB  
Article
Network Pharmacology and Experimental Verification to Unveil the Mechanism of N-Methyl-D-Aspartic Acid Rescue Humantenirine-Induced Excitotoxicity
by Xue-Jia Qi, Chong-Yin Huang, Meng-Ting Zuo, Meng-Die Gong, Si-Juan Huang, Mo-Huan Tang and Zhao-Ying Liu
Metabolites 2023, 13(2), 195; https://doi.org/10.3390/metabo13020195 - 28 Jan 2023
Cited by 1 | Viewed by 1776
Abstract
Gelsemium is a medicinal plant that has been used to treat various diseases, but it is also well-known for its high toxicity. Complex alkaloids are considered the main poisonous components in Gelsemium. However, the toxic mechanism of Gelsemium remains ambiguous. In this [...] Read more.
Gelsemium is a medicinal plant that has been used to treat various diseases, but it is also well-known for its high toxicity. Complex alkaloids are considered the main poisonous components in Gelsemium. However, the toxic mechanism of Gelsemium remains ambiguous. In this work, network pharmacology and experimental verification were combined to systematically explore the specific mechanism of Gelsemium toxicity. The alkaloid compounds and candidate targets of Gelsemium, as well as related targets of excitotoxicity, were collected from public databases. The crucial targets were determined by constructing a protein–protein interaction (PPI) network. Subsequently, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the bioprocesses and signaling pathways involved in the excitotoxicity corresponding to alkaloids in Gelsemium. Then, the binding affinity between the main poisonous alkaloids and key targets was verified by molecular docking. Finally, animal experiments were conducted to further evaluate the potential mechanisms of Gelsemium toxicity. A total of 85 alkaloids in Gelsemium associated with 214 excitotoxicity-related targets were predicted by network pharmacology. Functional analysis showed that the toxicity of Gelsemium was mainly related to the protein phosphorylation reaction and plasma membrane function. There were also 164 pathways involved in the toxic mechanism, such as the calcium signaling pathway and MAPK signaling pathway. Molecular docking showed that alkaloids have high affinity with core targets, including MAPK3, SRC, MAPK1, NMDAR2B and NMDAR2A. In addition, the difference of binding affinity may be the basis of toxicity differences among different alkaloids. Humantenirine showed significant sex differences, and the LD50 values of female and male mice were 0.071 mg·kg−1 and 0.149 mg·kg−1, respectively. Furthermore, we found that N-methyl-D-aspartic acid (NMDA), a specific NMDA receptor agonist, could significantly increase the survival rate of acute humantenirine-poisoned mice. The results also show that humantenirine could upregulate the phosphorylation level of MAPK3/1 and decrease ATP content and mitochondrial membrane potential in hippocampal tissue, while NMDA could rescue humantenirine-induced excitotoxicity by restoring the function of mitochondria. This study revealed the toxic components and potential toxic mechanism of Gelsemium. These findings provide a theoretical basis for further study of the toxic mechanism of Gelsemium and potential therapeutic strategies for Gelsemium poisoning. Full article
(This article belongs to the Special Issue Toxic Effects and Metabolic Regulations of Hazardous Chemicals in Animal-Derived Food)
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14 pages, 2439 KiB  
Article
A GABA Receptor Modulator and Semiochemical Compounds Evidenced Using Volatolomics as Candidate Markers of Chronic Exposure to Fipronil in Apis mellifera
by Vincent Fernandes, Kevin Hidalgo, Marie Diogon, Frédéric Mercier, Magaly Angénieux, Jérémy Ratel, Frédéric Delbac, Erwan Engel and Philippe Bouchard
Metabolites 2023, 13(2), 185; https://doi.org/10.3390/metabo13020185 - 26 Jan 2023
Viewed by 1825
Abstract
Among the various “omics” approaches that can be used in toxicology, volatolomics is in full development. A volatolomic study was carried out on soil bacteria to validate the proof of concept, and this approach was implemented in a new model organism: the honeybee [...] Read more.
Among the various “omics” approaches that can be used in toxicology, volatolomics is in full development. A volatolomic study was carried out on soil bacteria to validate the proof of concept, and this approach was implemented in a new model organism: the honeybee Apis mellifera. Emerging bees raised in the laboratory in pain-type cages were used. Volatolomics analysis was performed on cuticles, fat bodies, and adhering tissues (abdomens without the digestive tract), after 14 and 21 days of chronic exposure to 0.5 and 1 µg/L of fipronil, corresponding to sublethal doses. The VOCs analysis was processed using an HS-SPME/GC-MS method. A total of 281 features were extracted and tentatively identified. No significant effect of fipronil on the volatolome could be observed after 14 days of chronic exposure. Mainly after 21 days of exposure, a volatolome deviation appeared. The study of this deviation highlighted 11 VOCs whose signal abundances evolved during the experiment. Interestingly, the volatolomics approach revealed a VOC (2,6-dimethylcyclohexanol) that could act on GABA receptor activity (the fipronil target) and VOCs associated with semiochemical activities (pheromones, repellent agents, and compounds related to the Nasonov gland) leading to a potential impact on bee behavior. Full article
(This article belongs to the Special Issue Toxic Effects and Metabolic Regulations of Hazardous Chemicals in Animal-Derived Food)
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17 pages, 2465 KiB  
Article
Metabolic Disposition and Elimination of Tritum-Labeled Sulfamethoxazole in Pigs, Chickens and Rats
by Jingchao Guo, Yaqi Sun, Yongxia Zhao, Lingli Huang, Dapeng Peng, Haihong Hao, Yanfei Tao, Dongmei Chen, Guyue Cheng, Xu Wang and Yuanhu Pan
Metabolites 2023, 13(1), 57; https://doi.org/10.3390/metabo13010057 - 30 Dec 2022
Cited by 5 | Viewed by 1983
Abstract
Sulfamethoxazole (SMZ), as a sulfa antibiotic, is often used in the treatment of various infectious diseases in animal husbandry. At present, SMZ still has many unresolved problems in the material balance, metabolic pathways, and residual target tissues in food animals. Therefore, in order [...] Read more.
Sulfamethoxazole (SMZ), as a sulfa antibiotic, is often used in the treatment of various infectious diseases in animal husbandry. At present, SMZ still has many unresolved problems in the material balance, metabolic pathways, and residual target tissues in food animals. Therefore, in order to solve these problems, the metabolism, distribution, and elimination of SMZ is investigated in pigs, chickens, and rats by radioactive tracing methods, and the residue marker and target tissue of SMZ in food animals were determined, providing a reliable basis for food safety. After a single administration of [3H]-SMZ (rats and pigs by intramuscular injection and chickens by oral gavage), the total radioactivity was rapidly excreted, with more than 93% of the dose excreted within 14 days in the three species. Pigs and rats had more than 75% of the administered volume recovered by urine. After 7 days of continuous administration, within the first 6 h, radioactivity was found in almost all tissues. The highest radioactivity and longest persistence in pigs was in the liver, while in chickens it was in the liver and kidneys, most of which was removed within 14 days. A total of six, three and three metabolites were found in chickens, rats and pigs, respectively. N4-acetyl-sulfamethoxazole (S1) was the main metabolite of SMZ in rats, pigs and chickens. The radioactive substance with the longest elimination half-life is sulfamethoxazole (S0), so S0 was suggested to be the marker residue in pigs and chickens. Full article
(This article belongs to the Special Issue Toxic Effects and Metabolic Regulations of Hazardous Chemicals in Animal-Derived Food)
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