Chrysin protects against kidney tissue damage caused by pemetrexed used in cancer treatment

Abstract

Pemetrexed (PMTX) is a multi-targeted, anticancer, antifolate agent that exerts its effect by disrupting the folate-dependent metabolic processes underlying cell proliferation. Kidney toxicity is a common side effect of anticancer agents. Chrysin (Chr) is a powerful antioxidant compound abundant in plant extracts, honey, and bee propolis. The aim of this study is to investigate the effect of the combined use of chrysin, a natural flavonoid, against the possible harmful effects of PMTX on kidney tissue. 50 male Wistar albino rats were divided into five groups: Control, Sham, PMTX, Chr, PMTX+Chr. Sham (1ml corn oil/day), CH (50mg/kg/day) by oral gavage, PMTX (1mg/kg/week) by i.p., PMTX+CH (PMTX;1mg/kg/week, CH;50mg/kg/day) were given at the same time every day. At the end of 4 weeks at the end of the study, blood and kidney tissues were collected. The malondialdehyde (MDA), superoxide dismutase (SOD) activities, and total antioxidant (TAS), total oxidant status (TOS), OSI also were measured. Blood-urea-nitrogen (BUN) and creatinine (Cr) analyzed by ELISA. Indicators of oxidative stress, MDA was elevated and antioxidant activity was reduced in the PMTX group compared to control and Sham (p <0,05). In the PMTX+Chr group, MDA, BUN, Cr and TOS were decreased, SOD and TAS was increased compared to PMTX group (p <0,05). We found that Chr exhibited ameliorative effects on PMTX induced nephrotoxicity increasing antioxidant activity and reducing oxidative damage.