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

Aim: Azithromycin is a semisynthetic macrolide antibiotic commonly indicated for use in middle ear, upper and lower respiratory tract infections, bronchitis, and communityacquired 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 (R). 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.