Influence of Azithromycin Treatment on Hepatic Lipid Peroxidation and Antioxidant Defence Systems of Rats

Abstract

Aim: Azithromycin is a semisynthetic macrolide antibiotic commonly indicated for use in middle ear, upper and lower respiratory tract infections, bronchitis, and community-acquired pneumonia with a well-established safety and efficacy profile. The antibiotic is usually well tolerated; however, it has been associated with rare cases of progressive cholestatic hepatitis and fulminant hepatic failure. This study was therefore designed to examine the effect of two doses of Azithromycin; 5.6 mg/kg body weight, (b.w.) and 11.2 mg/ kg b.w. on some hepatic and renal function indices, oxidative stress and antioxidant defense system in rats. Study Design: Toxicological, Histological and Biochemical study. Place and Duration of Study: Biochemistry Unit, Department of Chemical Sciences, Faculty of Natural Sciences, Ajayi Crowther University, Oyo, Nigeria between March 2012 and April 2012. Methodology: Thirty rats (Wistar strain) weighing between 180 – 200 g were randomly assigned into three treatment groups of ten animals each; Group I (Control) did not receive any drug, Group II received 5.6 mg/ kg b.w. and Group III received 11.2mg/ kg b.w. Azithromycin by oral gavage twice daily for seven days. Results: Urea, Creatinine and Bilirubin levels were significantly (p=0.05) elevated in the plasma of the rats that received 5.6 mg/ kg b.w. and 11.2mg/ kg b.w. by 20.0% and 35.0%, 78.0% and 130.0%, and 14.0% and 47.4% respectively when compared to the control. Activities of some marker enzymes; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and Gamma-glutamyl transferase (GGT) were also significantly increased (p=0.05) in the plasma of treated animals by 19.0% and 36.6%, 27.0% and 36.4%, 16.0% and 23.5%, and 43.9% and 80.5% respectively. Also, there was a significant increase (p=0.05) in plasma Triglycerides, Total cholesterol, HDL- and LDL-cholesterol in the treated animals by 20% and 31.2%, 19% and 35.4%, 24% and 74.3%, and 33% and 35.2% respectively. Furthermore, the two doses of Azithromycin significantly (p=0.05) reduced the levels of hepatic Ascorbic acid, Glutathione (GSH) and activities of Glutathione-S-transferase (GST) by 35%, 66.3% and 34% and 56.1%, 45% and 50%, respectively. In addition, there was a significant decrease in the activities of hepatic Catalase (CAT), and Superoxide dismutase (SOD) by 67.4% and 43.0%, and 43% and 50% respectively in the two treated group. These were accompanied by a significant increase (p=0.05) in hepatic lipid peroxidation (LPO) by 81% and 91.6% respectively in the treated groups. The histology of the liver revealed sinusoidal and portal congestion and a mild periportal cellular infiltration by mononuclear cells, by Zithromax 500®. Likewise, kidney histopathology revealed severe cortical congestion and hemorrhage and few tubules containing protein casts in the treated group. Conclusion: In conclusion, the administration of 5.6 mg/ kg b.w. and 11.2mg/ kg b.w. of Azithromycin induced marked renal and liver damage, oxidative stress and altered the antioxidant status in rats.