Protective Effects of the Hydroalcoholic Extract of Capparis spinosa L. Against Cyclophosphamide-Induced Nephrotoxicity in Mice

Abstract

Background: Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs despite its toxic side effects, including nephrotoxicity, hematotoxicity, mutagenicity, and immunotoxicity. Capparis spinosa is a multipurpose plant that contains a number of chemically active and diverse secondary metabolites, particularly flavonoids. Rutin and quercetin are two major flavonoids in the caper plant. Objectives: This study was undertaken to investigate the protective effect of Capparis spinosa L. extract on nephrotoxicity induced by cyclophosphamide in mice. Methods: In this experimental study, 40 male Swiss albino mice (20 - 25 g) were randomly divided into five groups with each group consisting of eight mice. Mice were pretreated with C. spinosa extract (CSE) orally in doses of 100, 200 and 400 mg/kg for five consecutive days, and CP (200 mg/kg, ip) was administrated on the fifth day 1 hour after the last dose of extract. The animals were sacrificed on the sixth day. Blood samples were collected to determine the serum creatinine (Cr) and blood urea nitrogen (BUN) levels. The malondialdehyde (MDA) and glutathione (GSH) levels were assayed in kidney tissue. The right kidney was maintained in 10% formalin for hematoxylin and eosin staining and histological examination. Results: Different plant parts (fruit, leaves, and petals) were examined for antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl assay, and leaf extract was used to determine nephroprotective effects. Results showed a significant increase in the levels of MDA, Cr, and BUN and a reduction of GSH by CP administration. Pre-treatment with CSE decreased the levels of MDA, Cr, and BUN. GSH increased in all doses, but the most significant alteration was observed in the doses of 200 and 400 mg/kg (P < 0.05). The nephroprotective effect of the CSE was confirmed by the histological examination of the kidneys. Conclusions: Our results indicate that CSE ameliorates biochemical indices and oxidative stress parameters against CP-induced nephrotoxicity.