الفهرس | Only 14 pages are availabe for public view |
Abstract Tamoxifen, a synthetic non-steroidal antagonist of estrogen receptor (ER) in breast tissue, has been used for more than 30 years to treat breast cancer in women and men. However, it behaves as an agonist in other tissues such as endometrium so, it could be characterized as a mixed agonist/antagonist.With the wide spread therapeutic use of tamoxifen, the side effects of the drug particularly its cytotoxicity in liver has been arise. Many cases of tamoxifen-induced hepatotoxicity have been reported including toxic hepatitis, massive hepatic steatosis, multifocal hepatic fatty infilteration,hepatic necrosis, hepatic cirrhosis and even hepatic cell carcinoma. Reactive oxygen species over production and apoptosis could be involved in the mechanisms of TAM-induced hepatotoxicity.N-acetylcysteine (NAC), the acetylated variant of the amino acid Lcysteine, is an excellent source of sulfhydryl group (SH) and can act as a precursor for glutathione (GSH) resulting in promoting detoxification and acting directly as free radical scavengers. NAC has historically been used as a mucolytic agent in a varity of respiratory illnesses (e.g.chronic bronchitis).However, it appears also to have beneficial effects in conditions characterized by decreased GSH or oxidative stress such as HIV infection,cancer, heart disease and cigarette smoking. NAC has been used extensively in the manangement of acetaminophen poisoning caused by GSH depletion and glutathione reduction. NAC also act as a chelating agent in the treatment of acute heavy metal poisoning. |