Doxorubicin toxicity can be ameliorated during antioxidant L-carnitine supplementation.
Doxorubicin toxicity can be ameliorated during antioxidant L-carnitine supplementation.
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DOI：
10.4161/oxim.3.6.14416
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发表时间：
2010-11
影响因子：
--
通讯作者：
Sayed-Ahmed MM
中科院分区：
文献类型：
--
作者：
Alshabanah OA;Hafez MM;Al-Harbi MM;Hassan ZK;Al Rejaie SS;Asiri YA;Sayed-Ahmed MM
阿霉素是一种广泛用于治疗不同类型实体瘤的抗生素。本研究探讨抗氧化剂左旋肉碱是否能减轻阿霉素引起的肝损害。雄性Wistar白化大鼠分为6组：1组腹腔注射生理盐水，连续10 d；2、3、4组每隔一天注射一次阿霉素（3 mg/kg， 1次），累积剂量分别为6、12、18 mg/kg。第五组连续10天注射左旋肉碱（200 mg/kg，每日1次），第六组给予阿霉素（18 mg/kg）和左旋肉碱（200 mg/kg）。高累积剂量多柔比星（18 mg/kg）显著提高了谷丙转氨酶、碱性磷酸酶、总胆红素、硫代巴比托酸活性物质（TBARs）、总硝酸盐/亚硝酸盐（NOx）生化水平p < 0.05，降低了谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSHP x）、谷胱甘肽-s转移酶（GST）、谷胱甘肽还原酶（GR）和过氧化氢酶（CAT）活性p < 0.05。real - time PCR证实了阿霉素对抗氧化基因活性的影响，与对照组相比，肝组织中抗氧化基因的表达水平显著降低p < 0.05。有趣的是，补充左旋肉碱完全逆转了阿霉素诱导的生化和基因表达水平到控制值。综上所述，本研究数据表明，补充左旋肉碱可以通过降低氧化应激，保持抗氧化酶的活性和基因表达水平来预防阿霉素给药过程中抗氧化防御能力的降低。
Doxorubicin is an antibiotic broadly used in treatment of different types of solid tumors. The present study investigates whether L-carnitine, antioxidant agent, can reduce the hepatic damage induced by doxorubicin. Male Wistar albino rats were divided into six groups: group 1 was intraperitoneal injected with normal saline for 10 consecutive days; group 2, 3 and 4 were injected every other day with doxorubicin (3 mg/kg, i.p.), to obtain treatments with cumulative doses of 6, 12 and 18 mg/kg. The fifth group was injected with L-carnitine (200 mg/kg, i.p.) for 10 consecutive days and the sixth group was received doxorubicin (18 mg/kg) and L-carnitine (200 mg/kg). High cumulative dose of doxorubicin (18 mg/kg) significantly increases the biochemical levels of alanine transaminase, alkaline phosphatase, total bilirubin, thiobarbituric acid reactive substances (TBARs), total nitrate/nitrite (NOx) p < 0.05 and decrease in glutathione (GSH ), superoxide dismutase (SOD), glutathione peroxidase (GSHP x), glutathione-s-transferase (GST), glutathione reductase (GR) and catalase (CAT) activity p < 0.05. The effect of doxorubicin on the activity of antioxidant genes was confirmed by real time PCR in which the expression levels of these genes in liver tissue were significantly decrease compared to control p < 0.05. Interestingly, L-carnitine supplementation completely reversed the biochemical and gene expression levels induced by doxorubicin to the control values. In conclusion, data from this study suggest that the reduction of antioxidant defense during doxorubicin administration resulted in hepatic injury could be prevented by L-carnitine supplementation by decreasing the oxidative stress and preserving both the activity and gene expression level of antioxidant enzymes.
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影响因子：
--
作者：
Essick EE;Sam F
通讯作者：
Sam F
影响因子：
1.8
作者：
Karaman, A;Fadillioglu, E;Yilmaz, Z
通讯作者：
Yilmaz, Z
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作者：
Chang, BJ;Nishikawa, M;Inoue, M
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Inoue, M
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作者：
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通讯作者：
Aral, Erinc
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14
作者：
Injac, Rade;Perse, Martina;Strukelj, Borut
通讯作者：
Strukelj, Borut