Tinospora cordifolia ameliorates urotoxic effect of cyclophosphamide by modulating GSH and cytokine levels

Abstract

Cyclophosphamide (CP) is a commonly used anti-cancer drug which causes toxicity by its reactive metabolites. In this study we investigated the effect of Tinospora cordifolia on urotoxicity induced by acute dose of CP using Swiss albino mice model. Administration of an alcoholic extract of the plant T. cordifolia (Family: Menispermaceae) (200 mg/kg i.p.) for 5 days reduced CP (1.5 mmol/kg body wt. i.p.) induced urotoxicity as evident from the morphological analysis of bladder, decreased the relative bladder and liver weights and also decreased level of urea nitrogen and protein in blood as well as urine. Severely inflamed and dark coloured urinary bladders of the CP alone treated animals were found to be normalized by the treatment of T. cordifolia. GSH content, which was drastically reduced by CP administration in both bladder and liver was enhanced by treatment with T. cordifolia. Histopathological analysis of the bladder of CP alone-treated group showed severe necrotic damage where as the T. cordifolia-treated group showed normal bladder architecture. The lowered levels of cytokines IFN-γ, IL-2, after CP treatment were found to be increased in treated animals. At the same time the level of pro-inflammatory cytokine TNF-α, which was elevated during CP administration, was significantly reduced by extract administration. This study clearly demonstrates uroprotective role of T. cordifolia from CP induced toxicities by modulating GSH and pro-inflammatory cytokine levels.