Protective effects of Suberoylanilide hydroxamic acid and Dapagliflozin administration on liver of diabetic rats

Background Type 2 diabetes mellitus (T2DM) is common metabolic disorders. T2DM patients had 2-fold increase to get liver disorders. Evidence that some antidiabetic substances treated liver disorders in T2DM patients is evolving. Current study aimed to investigate hepatoprotective actions of Suberoylanilide hydroxamic acid (SAHA) and dapagliflozin (DAPA) in T2DM rats. Methods T2DM occured by high fat diet (HFD) and single Streptozotocin (STZ) injection (35 mg/kg i.p.). Forty rats sorted into 4 groups: NC (negative control), T2DM, T2DM + SAHA (5 mg/kg/i.p. for 8 weeks) and T2DM + DAPA (1mg/kg/p.o. for 8 weeks). At experimental end, levels of fasting blood glucose (FBG), fasting insulin, hepatic function tests [gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, albumin, total protein], lipid profiles [total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG)] measured in serum. Hepatic tissue homogenization prepared for estimating oxidative stress biomarkers [glutathione (GSH), malonaldehyde (MDA), superoxide dismutase (SOD)]. Hepatic histopathological examination made under light microscope. Results Diabetic rats had significant rise in liver weights and hepatic enzymes (AST, ALT, GGT, total bilirubin), lipid profile [TG, TC, LDL-C) in serum, and elevation in MDA in liver homogenate, but significant decline in total proteins, albumin, HDL-C) in serum and SOD, GSH in liver homogenate. These changes associated with histopathological changes in liver tissue as degeneration, vacuolation of hepatocytes, dilatation, and congestion of portal veins with lymphocytic infiltration. SAHA and DAPA treatment decreased liver weights, FBG, insulin, insulin resistance (IR), AST, ALT, GGT, bilirubin, TG, TC, LDL-C. SAHA and DAPA increased antioxidant enzymes (GSH, SOD) levels, serum total protein, albumin and HDL-C. Interestingly, DAPA was better that SAHA in improving liver enzymes, lipid profile, decreased FBG but SAHA was better in improving antioxidants as SOD, insulin levels and IR. Also, there were marked improvements in liver histopathological changes in SAHA and DAPA groups that were better in SAHA group. Conclusions Suberoylanilide hydroxamic acid and dapagliflozin represent an approach to protect liver versus DM-induced disorders via suppression oxidative stress, improve lipid profile, hyperglycemia and IR progression thus conserving liver functions and structure.