Protective effect of atorvastatin on oxidative stress in streptozotocin‐induced diabetic rats independently their lipid‐lowering effects

Abstract

In the present study, we investigate the effects of atorvastatin on the lipid profile, oxidative stress, and liver enzyme markers, and its protective activity against diabetic complications, in streptozotocin (STZ)-induced diabetic rats. Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and high-density lipoprotein (HDL) levels, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities, were measured 7 weeks after the administration of STZ and atorvastatin. Thiobarbituric acid reactive substances (TBARS), non-protein associated sulfhydryl (NP-SH), total sulfhydryl (T-SH), and nitric oxide (NO) levels were measured to evaluate oxidative stress. Atorvastatin was found to inhibit ALT and AST activities and to reduce FBG levels in rats with STZ-induced diabetes. Moreover, atorvastatin treatment significantly reduced lipid peroxidation in kidney, heart, and eye tissues (P < 0.001, for all), and resulted in a significant increase in NP-SH levels in brain tissues (P < 0.001). Total NO and nitrate levels increased significantly after atorvastatin treatment (P < 0.01). Our results revealed that atorvastatin has a protective effect against STZ-induced oxidative damage by reducing TBARS levels and increasing NP-SH levels, has a hepatoprotective effect by decreasing ALT and AST activities. It also shows the antihyperglycemic activity by lowering FBG levels. K E Y W O R D Satorvastatin, diabetes mellitus, lipid peroxidation, liver enzymes, streptozotocin (STZ)

Multiparticulate Systems of Ezetimibe Micellar System and Atorvastatin Solid Dispersion Efficacy of Low-Dose Ezetimibe/Atorvastatin on High-Fat Diet-Induced Hyperlipidemia and Hepatic Steatosis in Diabetic Rats

“…This group had a moderate steatosis and inflammatory cell infiltration, as well as an absence of ballooning degeneration ( Figure 6B). Similar values of inflammation and ballooning with high steatosis values have been described in previous studies with different treatments of ezetimibe or atorvastatin in insulin-resistant obese rats [1]. These results match the changes in the visual appearance of the liver samples ( Figure S1).…”

“…Similar NASH scores were observed in different studies on diabetic rats fed a high-fat diet [18]. These degenerations in liver tissue are related to the high lipid levels and the oxidative stress observed in other studies with diabetic animals fed a high-fat diet [1,12]. steatosis.…”

“…GK rats fed a high-fat diet (HFD group) exhibited a significant (p < 0.05) increase in TC (53.65%), TG (72.69%), and LDL (145.11%), and a significant decrease (p < 0.05) in HDL (43.95%) compared with the control group ( Table 1). The use of diabetic rats causes a substantial reduction in the hepatic LDL receptor, increasing the highest levels of cholesterol and LDL [1,2]. The surfactant Kolliphor RH40 may inhibit the efflux transporter (P-glycoprotein) and improve the elimination of fatty acids from liver cells [37,39].…”

“…This hepatic damage is manifested in liver steatosis and inflammation of the hepatic cells. Non-alcoholic steatohepatitis (NASH) is also characterized by a high level of cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) in individuals with hyperlipidemia [ 1 ]. The accumulation of LDL and high values of transaminases such as alanine transaminase (ALT) and aspartate transaminase (AST) are indicative of significant hepatic steatosis in diabetic patients and are difficult to manage with current available therapies [ 1 ].…”

“…Non-alcoholic steatohepatitis (NASH) is also characterized by a high level of cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) in individuals with hyperlipidemia [ 1 ]. The accumulation of LDL and high values of transaminases such as alanine transaminase (ALT) and aspartate transaminase (AST) are indicative of significant hepatic steatosis in diabetic patients and are difficult to manage with current available therapies [ 1 ]. Animal models, such as Goto-Kakizaki (GK) rats are especially useful as models of diabetic dyslipidemia for the efficacy studies of different pharmacological treatments [ 2 ].…”