Fenofibrate Potentiates the Antihyperglycemic, Antidyslipidemic and Hepatoprotective Activity of Pioglitazone in Alloxan-Induced Diabetic Rats
Md. Tanjir Islam
Department of Pharmacy, Southeast University, Banani, Dhaka, Bangladesh.
Md. Shahid Sarwar
Department of Pharmacy, Southeast University, Banani, Dhaka, Bangladesh.
A. F. M. Towheedur Rahman
Department of Pharmacy, North South University, Bashundhara, Dhaka, Bangladesh.
Md. Asaduzzaman
Department of Pharmacy, Southeast University, Banani, Dhaka, Bangladesh.
Yusuf Ali
Department of Pharmacy, Southeast University, Banani, Dhaka, Bangladesh.
Shaheda Zannah
Department of Pharmacy, Southeast University, Banani, Dhaka, Bangladesh.
Mamunur Rashid *
Department of Pharmacy, Southeast University, Banani, Dhaka, Bangladesh and Department of Pharmacy, Rajshahi University, Rajshahi, Bangladesh.
*Author to whom correspondence should be addressed.
Abstract
Aim: The present research was designed to investigate the hypoglycemic, hypolipidemic and hepatoprotective activity of the fixed dose combination of pioglitazone and fenofibrate.
Methodology: For the study purpose, pioglitazone at a dose of 15 mg/70 kg body weight (BW) and fenofibrate at a dose of 72.5 mg/70 kg BW were administered on alloxan (120 mg/kg BW) induced diabetic rats. Both the drugs (pioglitazone and fenofibrate), singly and in combination, separately were tested in vivo for 14 days (two weeks) to determine blood glucose level, lipid profile and hepatoprotective activity using Long-Evans male rats as test animals. In addition, to investigate any possible side effects of the combined therapy, the survival rate of rats were also measured.
Results: The study showed that in alloxan induced diabetic rats, combination therapy significantly decreased the blood glucose level from 16.00±0.01 to 7.85±0.03 mmol/L two hours later of last dose administration in comparison to the diabetic control group, after daily treatment for two weeks. In case of dyslipidemic effect, combination therapy reduced total cholesterol level by 31%, triglyceride level by 46% and LDL-cholesterol level by 37% significantly and increased HDL-cholesterol level by 77% in comparison with their respective diabetic control groups. It was also observed that combination therapy decreased alanine transaminase (ALT) level by 53% and aspartate transaminase (AST) level by 40% in comparison to diabetic control group effectively. These changes were significantly better than those of pioglitazone and fenofibrate monotherapy. No rats were died after combined treatment while the survival rates were 80%, 80% and 60% for pioglitazone, fenofibrate and diabetic groups (alloxan induced) respectively.
Conclusions: Our study suggests that the combination of pioglitazone and fenofibrate might be efficacious in patients with diabetic dyslipidemia and might provide better hepatoprotective activity in these patients.
Keywords: Alloxan, combination therapy, fenofibrate, hepatoprotection, pioglitazone.