Modulation of tamoxifen-induced hepatotoxicity by tamoxifen-phospholipid complex
Sunil K Jena1, Sarasija Suresh1, Abhay T Sangamwar2
1Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
Objectives:
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.
Methods:
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.
Key Findings:
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.
Conclusions:
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.
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