Sterol regulator element binding proteins (SREBPs) are a family of transcription factors involved in the biogenesis of cholesterol, fatty acids and triglycerides. They also regulate physiological functions of many organs, such as thyroid, brain, heart, pancreas and hormone synthesis. Beside the physiological effects, SREBPs participate in some pathological processes, diabetes, endoplasmic reticulum stress, atherosclerosis and chronic kidney disease associated with SREBP expression changes. In the liver, SREBPs are involved in the pathogenesis of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatitis and hepatic cancer. There are several SREBP inhibitors that have potential for treating obesity, diabetes and cancer. This review assesses the recent findings about the roles of SREBPs in the physiology of organs’ function and pathogenesis of liver diseases.

The main side effect of gentamicin is nephrotoxicity. The effect of cobalamin (Cob) was investigated on gentamicin nephrotoxicity in rats. Renal injury induced by i.p. injection of gentamicin (100 mg/kg) for 8 consecutive days. Cobalamin (6 mg/kg/day, i.p) treatment was done for 8 consecutive days as co-treatment and post-treatment protocol. Cobalamin significantly increased creatinine clearance levels and renal blood flow which were reduced by gentamicin. Also, cobalamin significantly improved serum electrolytes (sodium and potassium) levels which were disturbed by gentamicin. Cobalamin significantly compensated deficits in the antioxidant defense mechanisms, suppressed lipid per oxidation and ameliorated renal tissue damage mediated by gentamicin. The results of the current study indicated that cobalamin effectively protected the kidney tissue against gentamicin induced acute nephrotoxicity in rats. The antioxidant and anti-inflammatory activities can be supposed the main factors responsible for the nephroprotective effect of cobalamin.

Background and purpose: Nonalcoholic steatohepatitis (NASH) is considered a common and serious liver disease, which develops into cirrhosis, fibrosis, and even hepatocellular carcinoma. Oxidative stress is identified as an important factor in the induction and promotion of NASH. Allantoin is a natural and safe compound and has notable effects on lipid metabolism, inflammation, and oxidative stress. Therefore, this study was aimed to assess the role of allantoin on the oxidative stress and SIRT1/Nrf2 pathway in a mouse model of NASH. Experimental approach: C57/BL6 male mice received saline and allantoin (saline as the control and allantoin as the positive control groups). NASH was induced by a methionine-choline deficient diet (MCD). In the NASH-allantoin (NASH-Alla) group, allantoin was injected for 4 weeks in the mice feeding on an MCD diet. Afterward, histopathological, serum, oxidative stress, and western blot evaluations were performed. Findings/Results: We found NASH provided hepatic lipid accumulation and inflammation. Superoxide dismutase (SOD) and glutathione (GSH) levels decreased, lipid peroxidation increased, and the expression of SIRT1 and Nrf2 downregulated. However, allantoin-treatment decreased serum cholesterol, ALT, and AST. Liver steatosis and inflammation were improved. Protein expression of SIRT1 and Nrf2 were upregulated and SOD, CAT, and GSH levels increased and lipid peroxidation decreased. Conclusion and implications: It seems that the antioxidant effects of allantoin might have resulted from the activation of SIRT1/Nrf2 pathway and increase of cellular antioxidant power.

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