Background: Type 2 diabetes mellitus (T2DM) patients have hepatic disorders risk. This study investigated liver-protective effects of suberoylanilide hydroxamic acid (SAHA) and dapagliflozin (DAPA) in T2DM rats. 
 
Methods: T2DM induced 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. 
 
Result: After 8 weeks treatment, diabetic rats showed elevated FBG, insulin, liver enzymes (GGT, ALT, AST), bilirubin, TG, TC, LDL-C, MDA, with reductions in albumin, proteins, HDL-C, GSH, SOD. Histopathological liver damage observed. SAHA and DAPA improved metabolic, oxidative stress and liver function. DAPA was effective in improving FBG and lipid profiles, while SAHA showed effective on insulin resistance and antioxidant. Histological liver improvements were more pronounced in SAHA group. SAHA and DAPA offer hepatoprotection in T2DM by improving oxidative stress, lipid metabolism and insulin sensitivity and preserving liver structure.

Protective Effects of Suberoylanilide Hydroxamic Acid and Dapagliflozin Administration on the Liver of Type 2 Diabetic Rats