EVALUATION OF THE POSSIBLE PROTECTIVE EFFECT OF METFORMIN IN CISPLATIN - INDUCED NEPHROTOXICITY IN ADULT MALE ALBINO RATS

Abstract

Backgrounds: Clinical use of cisplatin is limited by its nephrotoxicity as cisplatin -induced oxidative stress which leads ultimately to kidney dysfunction. Objective: Evaluation of the nephron-protective effect of metformin against nephrotoxicity induced by cisplatin in adult albino rats. Materials and Methods: Sixty adult male albino rats were divided randomly into 6 equal groups: Group I (control group) was injected with 1 ml isotonic saline solution intraperitoneally (I.P). Group 2 was injected with single dose of cisplatin I.P 3.5mg/kg. Group 3 was injected with single dose of cisplatin I.P 7.5 mg/kg. Group 4 was given an oral dose of metformin (350 mg/kg /day for 10 days). Group 5 was given 100 mg kg/day metformin for 3 days before cisplatin injection I.P at a dose of 7.5 mg/kg on day four, and metformin continued for 7days after. Group 6 was given 350 mg kg/day metformin for 3 days before cisplatin injection I.P at a dose of 7.5 mg/kg on day four, and metformin continued for 7days after. Body weight of each rat was recorded on day 1, 4, 7 and 10 and average weight for each group was calculated. At the end of specified duration (10 days), rats were sacrificed and both kidneys were excised, processed and stained with Hematoxylin and Eosin for histopathological study and with Periodic Acid-Schiff (PAS) and Mallory’s stain stains for histochemical study. Results: Rats injected with high dose of cisplatin (7.5 mg/kg) showed more loss of average body weight and higher blood urea nitrogen (BUN) and serum creatinine (Cr) levels than those rats injected with 3.5 mg/kg cisplatin. Rat group injected with high dose of cisplatin (7.5 mg/kg) and given low dose metformin (100 mg/kg/day) showed less loss of average body weight and improved renal functions than rat group given high dose of cisplatin (7.5 mg/kg) and high dose of metformin (350 mg/kg/ day). Histopathological examination with H&E and histochemical examination with PAS and Mallory stains revealed mild glomerular, tubular and interstitial changes in cisplatin low dose group compared to cisplatin high dose group which showed more renal damages. Group given metformin low dose + cisplatin high dose showed less renal damage than those given high dose of cisplatin+ high dose metformin. Conclusion: Metformin has protective effects against cisplatin -induced nephrotoxicity in adult male albino rats.