Abstract
Diabetic-induced liver toxicity is a serious complication that cause significant metabolic dysfunction. L-ergothioneine (L-egt) is a bioactive nutraceutical obtained from mushrooms and certain food products, with reported cytoprotective, antioxidant and anti-inflammatory properties and potential to improve efficacy of existing therapy. Thus, this study evaluates the effects of L-egt, and/or metformin, on diabetes-induced liver injury. Diabetes was induced in male Sprague-Dawley rats using 10% fructose for two weeks, followed by a single low dose streptozotocin (STZ, 40 mg/kg i.p) injection. After induction of diabetes, animals were treated either with de-ionized water (DW), L-egt (35 mg/kg bwt), metformin (500 mg/kg bwt), or a combination of L-egt and metformin orally for seven weeks. Body weight and glucose were monitored during the experiment. At the completion of experiment, blood samples were collected, and liver tissue was excised for biochemical analysis, enzyme-link immunosorbent assay (ELISA) of various liver function biomarkers, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis of genes associated with inflammation, oxidative stress, and lipid metabolism, as well as histopathological evaluation. Diabetic animals showed liver hypertrophy, increased liver injury, hepatic triglycerides, oxidative stress, and hepatic inflammation. However, L-egt, and/or metformin, improved glycemic control, reduced liver injury, triglycerides, oxidative damage, inflammatory injury, and normalize liver histology by upregulating Nrf2/Sirt1, downregulate NF-kB/TGF-B1, and reduce SREBP1c/FAS expression. In conclusion, these results showed that combination of L-egt and metformin improve therapeutic efficacy than either treatment alone. Thus, L-egt can be used as an adjuvant to mitigate diabetes-induced liver complication.
Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats