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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Protective role of thymoquinone against liver damage induced by tamoxifen in female rats
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Protective role of thymoquinone against liver damage induced by tamoxifen in female rats

机译：胸腺醌对他莫昔芬诱导的雌性大鼠肝损伤的保护作用

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摘要

One of the major reasons for terminating a clinical trial is the liver toxicity induced by chemotherapy. Tamoxifen (TAM) is an anti-estrogen used in the treatment and prevention of hormone-dependent breast cancer. Tamoxifen therapy may cause hepatic injury. The seeds of Nigella sativa, which contain the active ingredient thymoquinone (TQ), have been used in folk medicine for diverse ailments. TQ is reported to possess anticancer and hepatoprotective effects. In this study, the protective effects of TQ against TAM-induced hepatotoxicity in female rats were evaluated. Four groups of rats were used: control; TAM; TQ; TAM+TQ. TAM (45 mg·(kg body mass)-1·day-1, by intraperitoneal injection (i.p.), for 10 consecutive days) resulted in elevated serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, and gamma glutamyl transferase, as well as depletion of reduced glutathione in the liver and accumulation of lipid peroxides. Also, TAM treatment inhibited the hepatic activity of superoxide dismutase. Further, it raised the levels of tumor necrosis factor alpha in the liver and induced histopathological changes. Pretreatment with TQ (50 mg·(kg body mass)-1·day-1; orally, for 20 consecutive days, starting 10 days before TAM injection) significantly prevented the elevation in serum activity of the assessed enzymes. TQ significantly inhibited TAM-induced hepatic GSH depletion and LPO accumulation. Consistently, TQ normalized the activity of SOD, inhibited the rise in TNF-α and ameliorated the histopathological changes. In conclusion, TQ protects against TAM-induced hepatotoxicity.
机译：终止临床试验的主要原因之一是化疗引起的肝毒性。他莫昔芬（TAM）是一种抗雌激素，用于治疗和预防激素依赖性乳腺癌。他莫昔芬疗法可能引起肝损伤。含有活性成分胸腺醌（TQ）的黑黑苜蓿种子已在民间医学中用于治疗各种疾病。据报道，TQ具有抗癌和保肝作用。在这项研究中，评估了TQ对TAM诱导的雌性大鼠肝毒性的保护作用。使用四组大鼠：对照组;对照组。 TAM; TQ; TAM + TQ。 TAM（45 mg·（kg体重）-1·day-1，通过腹腔注射（ip），连续10天）导致血清丙氨酸转氨酶，天冬氨酸转氨酶，碱性磷酸酶，乳酸脱氢酶，总胆红素水平升高，和γ-谷氨酰转移酶，以及减少肝脏中还原型谷胱甘肽的消耗和脂质过氧化物的积累。而且，TAM处理抑制了超氧化物歧化酶的肝活性。此外，它升高了肝脏中肿瘤坏死因子α的水平并诱导了组织病理学改变。用TQ预处理（50 mg·（kg体重）-1·day-1;口服，连续20天，从TAM注射前10天开始）可显着防止所评估酶的血清活性升高。 TQ显着抑制TAM诱导的肝GSH耗竭和LPO积累。一致地，TQ使SOD的活性正常化，抑制TNF-α的上升并改善组织病理学变化。总之，TQ可防止TAM诱导的肝毒性。

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