Chrysin abrogates cisplatin-induced oxidative stress, p53 expression, goblet cell disintegration and apoptotic responses in the jejunum of Wistar rats

Abstract

Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for the treatment of numerous forms of cancer, but it has pronounced adverse effects, namely nephrotoxicity, ototoxicity, neurotoxicity, hepatotoxicity, diarrhoea and nausea. CDDP-induced emesis and diarrhoea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants, possesses multiple biological activities, such as antioxidant and anti-inflammatory properties. In the present study, we investigated the protective effect of chrysin against CDDP-induced jejunal toxicity. The plausible mechanism of CDDP-induced jejunal toxicity includes oxidative stress, p53 and apoptosis via up-regulating the expression of caspase-6 and -3. Chrysin was administered to Wistar rats orally in maize oil. A single intraperitoneal injection of CDDP was given and the animals were killed after 24 h of CDDP injection. Chrysin ameliorated CDDP-induced lipid peroxidation, increase in xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6-phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin attenuated CDDP-induced goblet cell disintegration, enhanced expression of p53 and apoptotic tissue damage. Histological findings further substantiated the protective effects of chrysin against CDDP-induced damage in the jejunum. The results of the present study demonstrate that oxidative stress and apoptosis are closely associated with CDDP-induced toxicity and chrysin shows the protective efficacy against CDDP-induced jejunum toxicity possibly via attenuating the oxidative stress and apoptotic tissue damage.