Department of Pharmacology; College of pharmacy, King Saud University, Riyadh Kingdom of Saudi Arabia.
Oxid Med Cell Longev. 2010 Nov-Dec;3(6):428-33. doi: 10.4161/oxim.3.6.14416. Epub 2010 Nov 1.
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 were 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 increase the biochemical levels of alanine transaminase , alkaline phosphatase, total bilirubin, total carnitine, thiobarbituric acid reactive substances (TBARs), total nitrate/nitrite (NOx) p < 0.05 and decrease in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), 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 reverse 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.
多柔比星是一种广泛用于治疗不同类型实体瘤的抗生素。本研究旨在探讨抗氧化剂左旋肉碱是否可以减轻多柔比星引起的肝损伤。雄性 Wistar 白化大鼠被分为六组：第 1 组连续 10 天腹腔注射生理盐水；第 2、3 和 4 组每隔一天注射多柔比星（3mg/kg，ip），以获得累积剂量为 6、12 和 18mg/kg 的治疗。第 5 组连续 10 天注射左旋肉碱（200mg/kg，ip），第 6 组接受多柔比星（18mg/kg）和左旋肉碱（200mg/kg）。高累积剂量的多柔比星（18mg/kg）显著增加丙氨酸转氨酶、碱性磷酸酶、总胆红素、总肉碱、硫代巴比妥酸反应物质（TBARs）、总硝酸盐/亚硝酸盐（NOx）的生化水平，p<0.05，降低谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSHPx）、谷胱甘肽-S-转移酶（GST）、谷胱甘肽还原酶（GR）和过氧化氢酶（CAT）的活性，p<0.05。实时 PCR 证实了多柔比星对抗氧化基因活性的影响，与对照组相比，肝组织中这些基因的表达水平显著降低，p<0.05。有趣的是，左旋肉碱的补充完全逆转了多柔比星引起的生化和基因表达水平，使其恢复到对照值。总之，本研究的数据表明，多柔比星给药期间抗氧化防御的降低导致肝损伤，可通过左旋肉碱的补充来预防，其机制可能是通过降低氧化应激并维持抗氧化酶的活性和基因表达水平。
