Comparative Study of the Protective Effect of N-Acytel Cysteine and Melatonin on Methotrexate Induced Renal Toxicity in Males Albino Rats

Abstract

Background: Methotrexate (MTX) is widely used as a cytotoxic chemotherapeutic agent for malignancies as well as in the treatment of various inflammatory diseases. MTX treatment has been associated with renal toxicity. The current study was conducted to assess the potential protective role of N-acetylcysteine and/or melatonin in attenuation of methotrexate-induced renal damage in MTX intoxicated male albino rats.Methods: sixty, apparently healthy adult male albino rats weighed 150+10 gm were randomly divided into six groups; (group 1: negative control group, group 2: positive control (NAC treated) group, group 3: positive control (Melatonin treated) group, group 4: MTX treated group, group 5: MTX/NAC treated group, group 6: MTX/Melatonin treated group). The rats were treated once daily for 12 weeks by I.V injection of Methotrexate in a dose of 2 mg/kg ( 1 / 7 LD 50 ), N-acetylcysteine in a dose of 80 mg/kg ( 1 / 14 LD 50 ) and Melatonin: in a daily dose of 10 mg/kg ( 1 / 36 LD 50 ) in the tail veins of rats and blood samples were obtained at the end of the 4 th , 8 th and 12 th weeks and were prepared for Creatinine examination. At the end of the study, kidney samples were obtained for histopathological examination.Results: A significant constant increase in the creatinine of the MTX-treated group (group 4) was observed throughout the study. Supplementation of NAC concomitantly with MTX in group 5 reduced significantly creatinine when compared to the non-supplemented group 4 that treated with MTX at the 4 th , 8 th and 12 th weeks. On the other hand, the use of the melatonin in combination with MTX in group 6 produced minimal non-significant reduction of the creatinine level relative to group 4 at the 4 th , 8 th and 12 th weeks (P>0.05). The previous chemical results were confirmed by the histopathological studies of the kidney that revealed maximal affection of the renal cortex in the MTX-treated rats (group 4). Kidney histopathologic findings were significantly milder when NAC was co-administered with MTX in groups 5. Meanwhile, deterioration of the renal cortical structure was observed in the MTXmelatonin treated rats (group 6).Conclusion: The present study showed that NAC has a superior protective effect than Melatonin against the renal damage induced by MTX in male albino rats.