Restoration of renal glutathione levels and histoarchitecture by N-acetylcysteine post cyclophosphamide exposure in rats

Abstract

Objective: To evaluate the protective potential of N-acetylcysteine against cyclophosphamide induced nephrotoxicity in rats.

Study design: Laboratory-based randomized controlled trial.

Place and Duration of Study: Department of Pharmacology and Therapeutics in collaboration with Clinicopathologic Laboratory, Army Medical College, Rawalpindi and National Institute of Health, Islamabad from  March to July 2018.

Material and Methods: A total of eighteen rats were divided into three equal groups. Group I served as the untreated control, Group II received a single intraperitoneal injection of cyclophosphamide (200mg/kg) and the Group III was administered an intraperitoneal injection of N-acetylcysteine (100mg/kg), once daily for five consecutive days followed by a single injection of cyclophosphamide one hour after the last dose. Twenty four hours after cyclophosphamide administration, the animals were sacrificed and the kidneys were evaluated for glutathione levels and histopathological changes. The results were statistically analyzed on SPSS version 21, for quantitative analysis one way ANOVA followed by post hoc Tukey test and for histopathologic analysis, Chi-Square test was applied.

Results: In the renal tissue, cyclophosphamide depleted the glutathione levels from the normal mean of 1.17ng/ml to 0.34ng/ml with p ? 0.05, alongside notable histopathologic changes including multiple foci of hemorrhages and dense leukocytic infiltrates. N-acetylcysteine reestablished the glutathione pools by raising the mean value upto 0.93ng/ml and preserved the normal histoarchitecture.

Conclusion: N-acetylcysteine can attenuate cyclophosphamide induced nephrotoxicity by preserving the normal glutathione levels and histoarchitecture.

Keywords: Cyclophosphamide, Glutathione, Histoarchitecture, N-acetylcysteine, Nephrotoxicity