School of Public Health, Southwest Medical University, Luzhou, 646000, China; Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, 646000, China.
School of Public Health, Southwest Medical University, Luzhou, 646000, China.
Toxicon. 2023 Nov;235:107313. doi: 10.1016/j.toxicon.2023.107313. Epub 2023 Oct 12.
Microcystins constitute a class of toxins synthesized by cyanobacteria and are known to inflict significant damage on the antioxidant defense system of living organisms, primarily targeting the liver. α-Lipoic acid (α-LA) is universally recognized as a potent antioxidant in biological systems. It exerts its beneficial effects through multiple mechanisms-directly neutralizing reactive oxygen species (ROS) and free radicals, and indirectly enhancing antioxidant defenses by facilitating the regeneration of glutathione (GSH). However, the precise modus operandi of α-LA's protective effect against Microcystin-LR-induced hepatotoxicity remains incompletely elucidated. The present study, therefore, employed α-LA to explore its protective role against Microcystin-LR exposure in mice. A model of Microcystin-LR-induced hepatic injury was established by administering Microcystin-LR into the peritoneal cavity of BALB/c mice daily over a two-week period. Thereafter, BALB/c mice were pre-treated with varying concentrations of α-LA via oral gavage for a duration of 7 days, followed by a 7-day exposure to Microcystin-LR. Our findings reveal that α-LA pre-treatment significantly mitigated hepatic pathologies in Microcystin-LR-exposed mice. Furthermore, α-LA administration led to a notable elevation in the activities and expression levels of nuclear factor erythroid 2-related factor 2, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione-indicative of its antioxidative capacity. Concurrently, a significant decrease was observed in the activities and expression levels of malondialdehyde and cytochrome P450 2E1. Consequently, α-LA emerges as a promising therapeutic candidate for the amelioration of liver oxidative damage subsequent to Microcystin-LR exposure.
微囊藻毒素是由蓝藻合成的一类毒素，已知会对生物体的抗氧化防御系统造成严重损害，主要针对肝脏。α-硫辛酸（α-LA）在生物系统中被普遍认为是一种有效的抗氧化剂。它通过多种机制发挥其有益作用——直接中和活性氧（ROS）和自由基，以及通过促进谷胱甘肽（GSH）的再生间接增强抗氧化防御。然而，α-LA 对微囊藻毒素-LR 诱导的肝毒性的保护作用的确切作用机制仍不完全清楚。因此，本研究采用 α-LA 来探索其在小鼠中对微囊藻毒素-LR 暴露的保护作用。通过每天向 BALB/c 小鼠腹腔内注射微囊藻毒素-LR，建立微囊藻毒素-LR 诱导的肝损伤模型。在为期两周的时间里，BALB/c 小鼠接受了不同浓度的 α-LA 经口灌胃预处理，持续 7 天，随后暴露于微囊藻毒素-LR 7 天。我们的研究结果表明，α-LA 预处理显著减轻了微囊藻毒素-LR 暴露小鼠的肝病理学变化。此外，α-LA 给药导致核因子红细胞 2 相关因子 2、超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽 S-转移酶和谷胱甘肽的活性和表达水平显著升高——表明其抗氧化能力。同时，丙二醛和细胞色素 P450 2E1 的活性和表达水平显著降低。因此，α-LA 作为一种有前途的治疗候选物，可用于改善微囊藻毒素-LR 暴露后肝脏的氧化损伤。
