Zemin Zhu , Muhammad Shahab , Shahab Uddin , Imdadullah , Muhammad Ishfaq
{"title":"黄曲霉毒素b1诱导的男性生殖毒性:人类和动物的生物激活、机制、分子途径和植物化学物质的缓解","authors":"Zemin Zhu , Muhammad Shahab , Shahab Uddin , Imdadullah , Muhammad Ishfaq","doi":"10.1016/j.toxicon.2025.108554","DOIUrl":null,"url":null,"abstract":"<div><div>Aflatoxins (AFTs) represent a major subclass of mycotoxins that are widely recognized as critical contaminants in both food systems and environmental matrices (soil, water, air dust). Among them, aflatoxin B1 (AFB1) is identified as the most toxic and biologically active compound, exhibiting a broad spectrum of deleterious effects, including nephrotoxicity, immunotoxicity, neurotoxicity, hepatotoxicity and genotoxicity. Increasing evidence has highlighted the role of AFB1 in impairing reproductive health, with a particular emphasis on AFB1-induced infertility in both humans and animals. The compound adversely affects the architecture and physiological functions of reproductive organs, leading to disrupted gametogenesis in males and consequent reductions in fertility rates. These testicular toxicities pose serious threats to public health, food security, and animal productivity. The molecular mechanisms implicated in AFB1-mediated reproductive damage include apoptosis, inflammation, autophagy, cell cycle dysregulation, and oxidative stress. Recently, naturally derived phytochemicals have emerged as promising countermeasures due to their low toxicity at appropriate doses and natural structural motifs. These bioactive compounds exert antioxidant, anti-inflammatory, and anti-apoptotic effects, thereby mitigating AFB1-induced germ cell toxicity. Additionally, certain phytochemicals modulate the biotransformation and detoxification of AFB1 in vivo, reducing its genotoxic potential and facilitating its excretion. This review provides a comprehensive analysis of AFB1-induced testicular toxicity in male mammals, with a focus on the underlying molecular pathways and protective roles of various plant-based agents. It further delineates the mechanistic basis for the anti-AFB1 activity of these phytochemicals, drawing attention to their shared properties and species-specific responses. Here, we identify existing gaps in current research and propose future directions to optimize phytochemical interventions. Overall, this review underscores the therapeutic potential of phytochemicals in alleviating AFB1-associated reproductive dysfunction through targeted modulation of critical signaling pathways.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"267 ","pages":"Article 108554"},"PeriodicalIF":2.4000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Aflatoxin B1-Induced male reproductive Toxicity: Bioactivation, mechanisms, molecular pathways, and Mitigation by phytochemicals in humans and animals\",\"authors\":\"Zemin Zhu , Muhammad Shahab , Shahab Uddin , Imdadullah , Muhammad Ishfaq\",\"doi\":\"10.1016/j.toxicon.2025.108554\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Aflatoxins (AFTs) represent a major subclass of mycotoxins that are widely recognized as critical contaminants in both food systems and environmental matrices (soil, water, air dust). Among them, aflatoxin B1 (AFB1) is identified as the most toxic and biologically active compound, exhibiting a broad spectrum of deleterious effects, including nephrotoxicity, immunotoxicity, neurotoxicity, hepatotoxicity and genotoxicity. Increasing evidence has highlighted the role of AFB1 in impairing reproductive health, with a particular emphasis on AFB1-induced infertility in both humans and animals. The compound adversely affects the architecture and physiological functions of reproductive organs, leading to disrupted gametogenesis in males and consequent reductions in fertility rates. These testicular toxicities pose serious threats to public health, food security, and animal productivity. The molecular mechanisms implicated in AFB1-mediated reproductive damage include apoptosis, inflammation, autophagy, cell cycle dysregulation, and oxidative stress. Recently, naturally derived phytochemicals have emerged as promising countermeasures due to their low toxicity at appropriate doses and natural structural motifs. These bioactive compounds exert antioxidant, anti-inflammatory, and anti-apoptotic effects, thereby mitigating AFB1-induced germ cell toxicity. Additionally, certain phytochemicals modulate the biotransformation and detoxification of AFB1 in vivo, reducing its genotoxic potential and facilitating its excretion. This review provides a comprehensive analysis of AFB1-induced testicular toxicity in male mammals, with a focus on the underlying molecular pathways and protective roles of various plant-based agents. It further delineates the mechanistic basis for the anti-AFB1 activity of these phytochemicals, drawing attention to their shared properties and species-specific responses. Here, we identify existing gaps in current research and propose future directions to optimize phytochemical interventions. Overall, this review underscores the therapeutic potential of phytochemicals in alleviating AFB1-associated reproductive dysfunction through targeted modulation of critical signaling pathways.</div></div>\",\"PeriodicalId\":23289,\"journal\":{\"name\":\"Toxicon\",\"volume\":\"267 \",\"pages\":\"Article 108554\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicon\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0041010125003290\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicon","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041010125003290","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Aflatoxin B1-Induced male reproductive Toxicity: Bioactivation, mechanisms, molecular pathways, and Mitigation by phytochemicals in humans and animals
Aflatoxins (AFTs) represent a major subclass of mycotoxins that are widely recognized as critical contaminants in both food systems and environmental matrices (soil, water, air dust). Among them, aflatoxin B1 (AFB1) is identified as the most toxic and biologically active compound, exhibiting a broad spectrum of deleterious effects, including nephrotoxicity, immunotoxicity, neurotoxicity, hepatotoxicity and genotoxicity. Increasing evidence has highlighted the role of AFB1 in impairing reproductive health, with a particular emphasis on AFB1-induced infertility in both humans and animals. The compound adversely affects the architecture and physiological functions of reproductive organs, leading to disrupted gametogenesis in males and consequent reductions in fertility rates. These testicular toxicities pose serious threats to public health, food security, and animal productivity. The molecular mechanisms implicated in AFB1-mediated reproductive damage include apoptosis, inflammation, autophagy, cell cycle dysregulation, and oxidative stress. Recently, naturally derived phytochemicals have emerged as promising countermeasures due to their low toxicity at appropriate doses and natural structural motifs. These bioactive compounds exert antioxidant, anti-inflammatory, and anti-apoptotic effects, thereby mitigating AFB1-induced germ cell toxicity. Additionally, certain phytochemicals modulate the biotransformation and detoxification of AFB1 in vivo, reducing its genotoxic potential and facilitating its excretion. This review provides a comprehensive analysis of AFB1-induced testicular toxicity in male mammals, with a focus on the underlying molecular pathways and protective roles of various plant-based agents. It further delineates the mechanistic basis for the anti-AFB1 activity of these phytochemicals, drawing attention to their shared properties and species-specific responses. Here, we identify existing gaps in current research and propose future directions to optimize phytochemical interventions. Overall, this review underscores the therapeutic potential of phytochemicals in alleviating AFB1-associated reproductive dysfunction through targeted modulation of critical signaling pathways.
期刊介绍:
Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee.
Toxicon''s "aims and scope" are to publish:
-articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms
-papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins
-molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins
-clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained.
-material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems.
-articles on the translational application of toxins, for example as drugs and insecticides
-epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged.
-articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon.
-review articles on problems related to toxinology.
To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.