Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

• Published in: Toxicology and applied pharmacology 2012-02, Vol.258 (3), p.315-329
• Main Authors: Khan, Rehan, Khan, Abdul Quaiyoom, Qamar, Wajhul, Lateef, Abdul, Tahir, Mir, Rehman, Muneeb U, Ali, Farrah, Sultana, Sarwat
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; Animals; Antineoplastic Agents - toxicity; ANTINEOPLASTIC DRUGS; APOPTOSIS; Apoptosis - drug effects; Bak; BENZOQUINONES; Biological and medical sciences; BIOLOGICAL STRESS; Caspase 3 - metabolism; CATALASE; Cisplatin; Cisplatin - toxicity; Colon - drug effects; Colon - pathology; Colon toxicity; CORN OIL; DAMAGE; Dose-Response Relationship, Drug; Flavonoids - administration & dosage; Flavonoids - pharmacology; GLUCOSE; GLUTATHIONE; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; INTRAPERITONEAL INJECTION; LARGE INTESTINE; Male; Medical sciences; NEOPLASMS; OXIDASES; OXIDATION; Oxidative stress; Oxidative Stress - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism; p38MAPK; RATS; Rats, Wistar; THERAPY; TOXICITY; Toxicology; Tumor Suppressor Protein p53 - metabolism; Up-Regulation - drug effects
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2011.11.013

Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea 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, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, 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 also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. [Display omitted] ► Cisplatin-induced colon toxicity is associated with oxidative stress and apoptosis. ► Chrysin abrogates cisplatin-induced phospho-p38MAPK, p53, Bak and caspase-3 expression. ► Chrysin abrogates cisplatin-induced goblet cell damage and histological alterations. ► Chrysin protects against cisplatin-induced apoptotic damages and oxidative stress.