Modulatory Effect of Lovastatin on Therapeutic Efficiency of Conventional Antidiabetics on Pancreatic and Cardiovascular Complications of Diabetes

The aim of the present study is to assess the possible modulatory effect of lovastatin (LOVA) on metformin (MET) and gliclazide (GLIC) on pancreatic and cardiovascular complications in rats with experimentally induced diabetes. Male Swiss rats were randomly assigned to seven groups. Group 1 served as normal control group. Group 2 served as diabetic control group, treated with streptozotocin (STZ) alone. Groups 3, 4, 5, 6 and 7 received LOVA, MET, GLIC, LOVA plus MET and LOVA plus GLIC, respectively, for 30 consecutive days after treatment with STZ. To evaluate the modulatory effect of LOVA, blood glucose level was assessed coupled with pancreatic tissue levels of oxidative stress markers including thiobarbituric acid reactive substances (TBARS) production, glutathione reduced (GSH) stores, total nitrite (NO2-) production as well as glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities. Degree of lipid derangement was evaluated by measuring serum levels of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, triglycerides (TGs), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C). Serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6), as well as blood fibrinogen (FBG) level and white blood cells (WBCs) count were evaluated to assess generalized inflammatory and hematological disorders. Combination of LOVA with either MET or GLIC significantly corrected STZ-induced alterations of serum levels of glucose, HMG-CoA reductase, TGs, TC, LDL-C, HDL-C, CRP and IL-6, tissue contents of TBARS, GSH, NO2-, GST and SOD, as well as blood FBG level and WBCs count as compared to either drug alone. LOVA combination with MET but not with GLIC could modulate serum HDL-C level, whilst LOVA combination with GLIC but not with MET could modulate pancreatic tissue CAT activity. These results show that combination of LOVA with MET or GLIC significantly modulates their effects on diabetes-induced pancreatic and cardiovascular complications, including hyperglycemia, oxidative and nitrosative stress, dyslipidemia, inflammatory disorders, hyperfibrinogenemia and leucocytosis.