流行病学研究显示，暴露于亚砷酸钠（NaAsO2）可引起糖尿病和肝毒性。二甲双胍（MET）是一种长期用于糖尿病治疗的口服降糖药物。此外，MET已被证明具有肝脏保护作用。本研究旨在研究MET对NaAsO2引起的肝毒性和葡萄糖耐量减低的影响。将小鼠分为四组：I组和II组分别连续五周接受蒸馏水和NaAsO2（10mg / kg，p.o.）；III组和IV组在前三周接受NaAsO2（10mg / kg，p.o.），并在NaAsO2之前的最后两周接受MET（125和250mg / kg，p.o.）。于第35天进行葡萄糖耐量试验。血清和组织参数也进行了评估。组织病理学检查显示NaAsO2引起的肝脏和胰腺损伤。NaAsO2导致高血糖、葡萄糖耐量降低以及肝功能酶显著增加。NaAsO2的给药显著降低了肝超氧化物歧化酶、过氧化物酶、谷胱甘肽过氧化物酶和总巯基含量，并增加了反应性硫代巴比妥酸物质的含量。此外，还引起肝脏一氧化氮含量的增加，以及肿瘤坏死因子α、核因子κB和半胱氨酸天冬酶-3的蛋白表达的增加。相反，MET（250mg / kg）的治疗显著改善了NaAsO2引起的生化和组织病理学变化。我们的研究结果表明，MET对NaAsO2引起的肝毒性和葡萄糖耐量减低的显著影响可能通过调节氧化应激，进而抑制炎症和细胞凋亡来发挥作用。版权所有©2023 Elsevier GmbH。保留所有权利。

Epidemiological studies have shown that exposure to sodium arsenite (NaAsO2) causes diabetes and hepatotoxicity. Metformin (MET), an oral hypoglycemic agent, has long been used in diabetes therapy. In addition, MET has been shown to have hepatoprotective effects. In this study, we investigated the effects of MET on NaAsO2-induced hepatotoxicity and glucose intolerance in mice.Mice were divided into four groups: Groups I and II received distilled water and NaAsO2 (10 mg/kg, p.o.) for five weeks, respectively. Groups III and IV were treated with NaAsO2 (10 mg/kg, p.o.) for three weeks, followed by MET (125 and 250 mg/kg, p.o.) for the last two weeks before NaAsO2. A glucose tolerance test was performed on day 35. The serum and tissue parameters were also evaluated.Histopathological examination revealed NaAsO2-induced liver and pancreatic damage. NaAsO2 caused hyperglycemia, glucose intolerance, and a significant increase in liver function enzymes. Administration of NaAsO2 significantly reduced hepatic superoxide dismutase, catalase, glutathione peroxidase, and total thiol levels and increased the content of reactive thiobarbituric acid substances. In addition, it led to an increase in liver nitric oxide levels and protein expression of tumor necrosis factor-α, nuclear factor kappa B, and cysteine-aspartic proteases-3. In contrast, treatment with MET (250 mg/kg) significantly improved NaAsO2-induced biochemical and histopathological changes.Our findings suggest that the significant effects of MET against NaAsO2-induced hepatotoxicity and glucose intolerance may be exerted via the regulation of oxidative stress, followed by suppression of inflammation and apoptosis.Copyright © 2023 Elsevier GmbH. All rights reserved.