L-ergothioneine and metformin alleviates liver injury in experimental type-2 diabetic rats via reduction of oxidative stress, inflammation, and hypertriglyceridemia

Type-2 diabetes (T2D) is associated with liver toxicity. L-ergothioneine (L-egt) has been reported to reduce toxicity in tissues exposed to injury, while metformin is commonly prescribed to manage T2D. Hence, this study evaluates the hepatoprotective role of L-egt, with or without metformin, in T2D male rats. A total of 36 adult male Sprague-Dawley rats were randomly divided into non-diabetic (n = 12) and diabetic (n = 24) groups. After induction of diabetes, animals were divided into six groups (n = 6) and treated orally either with deionized water, L-egt (35 mg/kg bodyweight (bwt)), metformin (500 mg/kg bwt), or a combination of L-egt and metformin for 7 weeks. Body weight and blood glucose were monitored during the experiment. Thereafter, animals were euthanized and liver tissue was excised for biochemical, ELISA, real-time quantitative PCR, and histopathological analysis. L-egt with or without metformin reduced liver hypertrophy, liver injury, triglycerides, oxidative stress, and inflammation. Also, L-egt normalized mRNA expression of SREBP-1c, fatty acid synthase, nuclear factor kappa B, transforming growth factor β1, nuclear factor erythroid 2-related factor 2, and sirtuin-1 in diabetic rats. Furthermore, co-administration of L-egt with metformin to diabetic rats reduced blood glucose and insulin resistance. These results provide support to the therapeutic benefits of L-egt in the management of liver complications associated with T2D.