Effects of Allium sativum extract on atazanavir induced Nephrotoxicity in male winstar rats

Abstract

Introduction of highly active antiretroviral therapy in 1998 in the treatment of HIV led to dramatic decrease in morbidity and mortality among HIV infected patients translating it into a chronic manageable condition. Atazanavir was a recommended first line therapy for HIV treatment. However, it is nephrotoxic with prolonged use and may lead to irreversible renal damage. Allium sativum, a common food supplement is known for its antioxidant properties but its nephroprotective properties in Atazanavir nephrotoxicity has not been studied. The present study investigated the effects of A. sativum extract on serum creatinine, Urea, Uric Acid and Electrolytes (Sodium, Potassium & Chloride) on male laboratory wistar rats. The study also determined effects of the A. sativum extract on kidneys histology. This was an experimental study conducted at the University of Eldoret, Department of Biological Sciences, Zoology laboratory. Thirty-nine (39) male wistar rats of approximately the same age and weighing between 150g- 250g were sourced from Chiromo campus of the University of Nairobi and transported to the University of Eldoret – zoology laboratory where they were allowed two weeks to acclimatize. During the acclimatization period all the experimental animals were accustomed to handling by the animal attendant. Thereafter, the animals were randomly divided into 3 groups (Control, Treatment and Intervention groups) of 13 animals each. Treatment group received Atazanavir 10mg/kg, Intervention group received Atazanavir (10mg/kg.bwt) and A. sativum extract (250mg/kg.bwt) while control group received normal saline (1.5ml). Administration of drugs was by gavage. Blood sampling was done twice (14 days apart) during pre-treatment and later 2 weekly for 6 weeks during treatment phase. The blood samples we used to determine electrolytes (Na+, K+& Cl-), nitrogenous metabolites (Creatinine and Urea) and Uric Acid levels using automated clinical Chemistry analyzer (Reflectron Automated Analyzer, Beckman, U.S.A). At the end of the study, 4 representative animals from each group were sacrificed and kidney tissue were harvested for histological examination. Quantitative data were expressed as Mean ± standard Error of Mean (SEM) and the difference of means among treatment groups was measured by one-way analysis of variance (ANOVA) followed by Tukey’s Honest Significant Difference test. Values were statistically significant when P < 0.05. The study showed that Atazanavir administration caused increased in Creatine, Urea, Electrolytes (Na+, K+& Cl-) and Uric acid while co-administered with A. sativum extract, the levels significantly (p<0.05) decreased to near normal as compared to control animals. Kidney tissue from experimental animals showed features of renal cell nephritis characterized by clear and enlarged podocytes, irregular infiltrating cells with hyperchromatic nuclei, marked pleomorphism and expanded mesangial matrix. The Atazanavir effects on the kidney histology were reversed when the treatment was co-administered with A. sativum extract. A. sativum extract exhibited nephroprotective activity. The findings of the present study showed that A. sativum extract ameliorates effects of Atazanavir leading to reduction in Creatinine, Urea, Electrolytes (Na+, K+& Cl-) and Uric Acid. Therefore, A. sativum extract can be further tested and recommended for use as a supplement in Atazanavir treatment.