Deoxynivalenol exposure-related male reproductive toxicity in mammals: Molecular mechanisms, detoxification and future directions DOI Creative Commons
Chongshan Dai, Zhihui Hao,

Dingkuo Liu

et al.

Environment International, Journal Year: 2025, Volume and Issue: 199, P. 109478 - 109478

Published: April 17, 2025

An increasing body of evidence indicates that exposure to widespread, environmental and food contaminants such as mycotoxins may cause endocrine disorders infertility. Deoxynivalenol (DON), which is a toxic secondary metabolite produced by Fusarium fungi, can lead multiple harmful effects in humans animals, hepatotoxicity, nephrotoxicity, immunotoxicity, gastrointestinal toxicity, neurotoxicity, genetic toxicity carcinogenicity. Recently, there has been growing concern about DON-induced male Exposure DON its metabolites damage the structure function reproductive organs, resulting impairment gametogenesis thus impaired fertility. Potential molecular mechanisms involve oxidative stress, inflammatory response, mitochondrial dysfunction, apoptosis, cell cycle arrest, pyroptosis, ferroptosis. Moreover, several signaling pathways, including nuclear factor-kappa B, mitogen-activated protein kinase, NLR family pyrin domain containing 3, factor erythroid 2-related 2, AMP-activated apoptotic microRNAs are involved these detrimental biological processes. Research shown antioxidants, small-molecule inhibitors, or proteins (such lactoferrin) supplementation potentially offer protective targeting pathways. This review comprehensively summarizes on mammals, underlying emphasizes potential small molecules therapeutics. In further, systematic risk assessment when at doses human health, in-depth precise mechanism investigation using emerging technologies, development more effective intervention strategies warrant urgent investigation.

Language: Английский

Ferroptosis and Charcot–Marie–Tooth Disease 1A: Emerging Evidence for a Pathogenic Association DOI Creative Commons

Jacob B. White,

Kayla L. Sanchez, António Currais

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 331 - 331

Published: March 11, 2025

Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy worldwide, presenting clinically as muscle weakness that progresses to impaired ambulation or quadriplegia with age. CMT1A, subtype, caused by a duplication in PMP22, encoding an essential membrane protein for Schwann cell myelin integrity. While mechanisms of neurodegeneration CMT1A are poorly understood, excessive oxidative stress, particularly lipid peroxidation, known pathological feature, and antioxidant therapy has reversed phenotype mouse model. For first time, we define pathogenic link between ferroptosis, form regulated death peroxidation hindered defenses. Human-derived fibroblasts showed greater susceptibility RSL3, pro-ferroptosis agent, compared controls, alongside several ferroptosis markers, including elevated peroxides depleted GPX4, critical anti-ferroptosis repressor. Similarly, transcriptomic analysis human iPSC-derived cells revealed activation cellular stress markers CMT1A. We propose chronic, sublethal ferroptotic mediated peroxide accumulation, depletes defenses cells, leading decompensation age, manifesting symptomatic disease. These results emphasize driver pathology, potentially revealing new therapeutic path.

Language: Английский

Citations

0
Deoxynivalenol exposure-related male reproductive toxicity in mammals: Molecular mechanisms, detoxification and future directions DOI Creative Commons
Chongshan Dai, Zhihui Hao,

Dingkuo Liu

et al.

Environment International, Journal Year: 2025, Volume and Issue: 199, P. 109478 - 109478

Published: April 17, 2025

An increasing body of evidence indicates that exposure to widespread, environmental and food contaminants such as mycotoxins may cause endocrine disorders infertility. Deoxynivalenol (DON), which is a toxic secondary metabolite produced by Fusarium fungi, can lead multiple harmful effects in humans animals, hepatotoxicity, nephrotoxicity, immunotoxicity, gastrointestinal toxicity, neurotoxicity, genetic toxicity carcinogenicity. Recently, there has been growing concern about DON-induced male Exposure DON its metabolites damage the structure function reproductive organs, resulting impairment gametogenesis thus impaired fertility. Potential molecular mechanisms involve oxidative stress, inflammatory response, mitochondrial dysfunction, apoptosis, cell cycle arrest, pyroptosis, ferroptosis. Moreover, several signaling pathways, including nuclear factor-kappa B, mitogen-activated protein kinase, NLR family pyrin domain containing 3, factor erythroid 2-related 2, AMP-activated apoptotic microRNAs are involved these detrimental biological processes. Research shown antioxidants, small-molecule inhibitors, or proteins (such lactoferrin) supplementation potentially offer protective targeting pathways. This review comprehensively summarizes on mammals, underlying emphasizes potential small molecules therapeutics. In further, systematic risk assessment when at doses human health, in-depth precise mechanism investigation using emerging technologies, development more effective intervention strategies warrant urgent investigation.

Language: Английский

Citations

0