Chrysin protects against cisplatin-induced colon, toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53
Chrysin protects against cisplatin-induced colon, toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53
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DOI：
10.1016/j.taap.2011.11.013
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发表时间：
2012-02-01
影响因子：
3.8
通讯作者：
Sultana, Sarwat
中科院分区：
文献类型：
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作者：
Khan, Rehan;Khan, Abdul Quaiyoom;Sultana, Sarwat
顺铂一种抗肿瘤药物，被广泛用作对抗多种形式癌症的首要疗法，但它具有明显的副作用，肾毒性、耳毒性等。CDDP诱导的呕吐和腹泻也是显著的毒性，可能是由于肠损伤。胡萝卜素（5，7-二羟基黄酮）是一种广泛存在于多种植物中的天然黄酮类化合物，具有抗氧化、抗肿瘤等多种生物活性。在本研究中，我们研究了白杨素对CDDP诱导的结肠毒性的保护作用。CDDP诱导的结肠毒性和损伤的可能机制包括氧化应激、p38 MAPK和p53的激活以及结肠上皮细胞凋亡（通过上调巴克和切割的caspase-3的表达）。以25和50 mg/kg体重的玉米油溶液经口给药Wistar大鼠，每日一次，连续14天。在第14天，以7.5 mg/kg体重的剂量单次腹膜内注射顺铂，并在顺铂注射24 h后对动物实施安乐死。甜菜碱改善CDDP诱导的脂质过氧化、黄嘌呤氧化酶活性、谷胱甘肽耗竭、抗氧化剂（过氧化氢酶、谷胱甘肽还原酶、谷胱甘肽过氧化物酶和葡萄糖-6-磷酸脱氢酶）和II相解毒酶（谷胱甘肽-S-转移酶和醌还原酶）活性降低。同时，CDDP可诱导杯状细胞崩解、p38 MAPK和p53磷酸化表达以及凋亡性组织损伤。组织学结果进一步支持白杨素对CDDP诱导的结肠损伤的保护作用。本研究的结果表明，白杨素对CDDP诱导的结肠毒性的保护作用与减轻氧化应激，激活p38 MAPK和p53，以及凋亡组织损伤有关。(C)2011 Elsevier Inc. All rights reserved.
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, antiinflammatory 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. (C) 2011 Elsevier Inc. All rights reserved.