Jena Sunil K, Suresh Sarasija, Sangamwar Abhay T
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
J Pharm Pharmacol. 2015 Sep;67(9):1198-206. doi: 10.1111/jphp.12422. Epub 2015 Apr 23.
Tamoxifen (TMX), a non-steroidal antiestrogen is a first-line drug in the treatment and prevention of all stages of estrogen-receptor-positive breast cancer. However, oxidative liver damage and hepatocarcinoma are the major problems associated with its long-term clinical use. The aim of this study was to investigate the ameliorative effect of phospholipid against TMX-induced hepatotoxicity.
Fifteen female Sprague-Dawley rats were divided into three groups with five rats in each group. Group I received only standard diet and distilled water for 28 days and served as normal. Group II received TMX per day p.o., for 28 days and served as control, and group III received TMX-phospholipid complex (TMX-PLC) per day p.o., for 28 days. Rats were examined for the effect of phospholipid on TMX-induced depletion of antioxidant enzymes, serum biochemical parameters and induction of lipid peroxidation.
Treatment with TMX-PLC significantly ameliorates the TMX-induced hepatotoxicity by diminishing the toxicity markers such lipid peroxidation, aspartate transaminase and alanine transaminase, accompanied by an increase in antioxidant enzyme activity in TMX-treated rats. Histological findings further confirmed the hepatoprotective effect of phospholipid.
Data of the present study suggests that phospholipid may prove as a useful component of combination therapy in cancer patients under the TMX treatment regimen.
他莫昔芬（TMX）是一种非甾体类抗雌激素药物，是治疗和预防各阶段雌激素受体阳性乳腺癌的一线药物。然而，肝氧化损伤和肝癌是其长期临床使用中存在的主要问题。本研究旨在探讨磷脂对TMX诱导的肝毒性的改善作用。
将15只雌性Sprague-Dawley大鼠分为三组，每组5只。第一组连续28天仅给予标准饮食和蒸馏水，作为正常对照组。第二组每天口服TMX，持续28天，作为对照组，第三组每天口服TMX-磷脂复合物（TMX-PLC），持续28天。检测磷脂对TMX诱导的抗氧化酶消耗、血清生化参数及脂质过氧化诱导的影响。
TMX-PLC治疗可通过降低脂质过氧化、天冬氨酸转氨酶和丙氨酸转氨酶等毒性标志物，显著改善TMX诱导的肝毒性，同时提高TMX处理大鼠的抗氧化酶活性。组织学结果进一步证实了磷脂的肝保护作用。
本研究数据表明，在TMX治疗方案下，磷脂可能是癌症患者联合治疗的有用成分。
