Azathioprine and methotrexate impaired the morphology and functions of the kidney in adult wistar rats.

Abstract

Azathioprine (50-150mg per day) and Methotrexate (2.5mg per week) are used in the treatment of cancer in adult Man. We evaluated the nephrotoxic effects of Azathioprine and Methotrexate in rats. Forty adult male wistar rats (150 - 230g) were used in the study. Group I was control. Experimental Groups II - V received oral administrations of 5mg/kg/bodyweight of Azathioprine per day, 15mg/kg/bodyweight of Azathioprine per day, 8mg/kg/bodyweight of Methotrexate per week and 20mg/kg/bodyweight of Methotrexate per week respectively for 35 days. Histological examinations of the kidney showed dose-dependent morphological anomalies such as irregular cyto-architecture and decreased diameters of the Urinary Space, shrunk Glomeruli and necrotic cells in Groups II – V. Statistical analyses showed dose-dependent elevated levels (P≤0.05) of superoxide dismutase and malondialdehyde in kidney homogenates of Groups II – V when compared to Group I. This implied increased oxidative stress in rats of Groups II – V. Evaluations of creatinine and urea concentrations showed dose-dependent significantly elevated levels (P≤0.05) in Groups II – V when compared to Group I. This study provided further evidence that the nephrotoxic activities of Azathioprine and Methotrexate could be due to generated increased oxidative stress, which resulted in impaired morphology and functions of the kidney in rats.

Key words: Azathioprine, methotrexate, kidney, morphology, functions.