Thymoquinone attenuates ifosfamide-induced Fanconi syndrome in rats and enhances its antitumor activity in mice
Thymoquinone attenuates ifosfamide-induced Fanconi syndrome in rats and enhances its antitumor activity in mice
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DOI：
10.1016/s0378-8741(98)00242-6
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发表时间：
1999-11-01
影响因子：
5.4
通讯作者：
Badary, OA
中科院分区：
文献类型：
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作者：
Badary, OA
用异环磷酰胺(IFO)诱导大鼠和小鼠Fanconi综合征(FS)模型，观察黑种草油的主要成分百里酚(TQ)对FS的影响及其抗肿瘤活性。大鼠每日注射异环磷胆碱(50 mg/kg/d)。连续5天诱发FS，表现为糖、电解质和有机酸消耗减少，血肌酐和尿素升高，内生肌酐清除率降低。大鼠口服TQ(5 mg/kg·d-1)，在IFO治疗前和治疗期间给药5天，可明显减轻IFO所致的肾损害。TQ能明显改善IFO所致的尿磷、糖尿、血肌酐和尿素升高，并显著提高肌酐清除率，并能显著阻止IFO所致的肾组织谷胱甘肽(GSH)耗竭和过氧化脂质蓄积。在荷Ehrlich腹水癌(EAC)小鼠模型上，饮水中加入TQ(10 mg/kg/d)可显著增强IFO(50 mg/kg/d，ip)的抗肿瘤作用。第1-4天和第15-18天)。此外，与IFO单独治疗相比，IFO联合TQ治疗的小鼠体重减轻和死亡率更低。提示TQ可能通过减轻IFO的肾毒性，提高其抗肿瘤活性，从而提高IFO的治疗效果。(C)1999爱思唯尔爱尔兰科学有限公司。保留所有权利。
The effect of thymoquinone (TQ), the main constituent of the Nigella sativa L. oil, on ifosfamide (IFO)-induced Fanconi syndrome (FS) and its antitumor activity were investigated in rats and mice, respectively. In rats, a daily injection of IFO (50 mg/kg per day, i.p.) for 5 days induced a FS characterized by wasting off glucose, electrolytes and organic acids, along with elevated serum creatinine and urea, as well as decreased creatinine clearance rate. Administration of TQ with the drinking water of rats, (5 mg/kg per day) for 5 days before and during IFO treatment, ameliorated the severity of IFO-induced renal damage. TQ significantly improved IFO-induced phosphaturia, glucosuria, elevated serum creatinine and urea, and significantly normalized creatinine clearance rate, Moreover, TQ significantly prevented IFO-induced renal glutathione (GSH) depletion and lipid peroxide accumulation. In mice bearing Ehrlich ascites carcinoma (EAC) xenograft, TQ (10 mg/kg per day) administered in drinking water significantly enhanced the antitumor effect of IFO (50 mg/kg per day, i.p. on days 1-4 and 15-18). Furthermore, mice treated with IFO in combination with TQ showed less body weight loss and mortality rate compared to IFO single therapy. These observations demonstrate that TQ may improve the therapeutic efficacy of IFO by decreasing IFO-induced nephrotoxicity and improving its antitumor activity. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.