1. SIRT5 safeguards against T-2 toxin induced liver injury by repressing iron accumulation, oxidative stress, and the activation of NLRP3 inflammasome.
- Author
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Huang J, Wang Y, Hu H, He K, Jiang X, Huang R, Liu T, Hu K, Guo X, Wang J, Zhang D, Li Q, Yang Z, and Wei Z
- Subjects
- Animals, Male, Mice, T-2 Toxin toxicity, Oxidative Stress drug effects, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Inflammasomes metabolism, Chemical and Drug Induced Liver Injury metabolism, Chemical and Drug Induced Liver Injury prevention & control, Chemical and Drug Induced Liver Injury pathology, Mice, Knockout, Sirtuins metabolism, Sirtuins genetics, Iron metabolism, Liver drug effects, Liver metabolism, Liver pathology, Mice, Inbred C57BL
- Abstract
T-2 toxin, a highly toxic trichothecene mycotoxin widely found in food and feed, poses a significant threat to human health as well as livestock and poultry industry. Liver, being a crucial metabolic organ, is particularly susceptible to T-2 toxin induced damage characterized by inflammation and oxidative stress. Despite the role of Sirtuin 5 (SIRT5) in mitigating liver injury has been confirmed, its specific impact on T-2 toxin induced liver injury remains to be elucidated. The objective of this study was to investigate the protective role of SIRT5 against T-2 toxin induced liver injury in mice. Following the oral administration of 1 mg/kg.bw of T-2 toxin for 21 consecutive days to SIRT5 knockout (SIRT5
-/- ) and wild-type (WT) male mice, liver assessments were conducted. Our findings demonstrated that aggravated hepatic pathological injury was observed in SIRT5-/- mice, accompanied by elevated malondialdehyde (MDA) and Fe levels, as well as enhanced expression of glutathione peroxidase 4 (GPX4), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, Gasdermin-D (GSDMD), tumour necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β). These results indicated that SIRT5 alleviated hepatic structural damage and dysfunction, while inhibiting oxidative stress, iron accumulation, and NLRP3 inflammasome activation. Analysis revealed a positive correlation among NLRP3 inflammasome activation, iron accumulation, and oxidative stress. Overall, our study demonstrated that SIRT5 mitigated liver injury induced by T-2 toxin through inhibiting iron accumulation, oxidative stress, and NLRP3 inflammasome activation, providing novel insights into the management and prevention of T-2 toxin poisoning., Competing Interests: Declaration of competing interest Zhengkai Wei reports financial support was provided by the Guangdong Basic and Applied Basic Research Foundation. Zhengkai Wei reports financial support was provided by Foundation for Innovative Research Groups of the National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)- Published
- 2024
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