亚洲传统医药

Abstract: Tamoxifen citrate (TAM) is widely used for the treatment of breast cancer, but it can be responsible for liver damage including hepatic carcinogenesis. The purpose of this study was to elucidate hepatoprotective effects, antioxidant protection abilities, and DNA fragmentation inhibitory effects of α-lipoic acid (LA) due to TAM-induced liver injury. A model of liver injury in female rats, i.e intraperitoneal (i.p.) injections of TAM at a dose of 45 mg/Kg/day for 7 successive days, was utilized. The dose of LA used as a protective agent in this study was 20 mg/Kg/day for 4 days before and for 14 days concurrently during TAM administration. Another group received LA for only 14 days concurrently during TAM administration as a curative agent. The model of TAM-intoxication treated with the protective and curative schedules of LA elicited significant declines in antioxidant enzymes [glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT)], reduced liver levels of glutathione (SGH) and tumour necrosis factor-α (TNF-α) with concomitant significant elevations in TBARS (thiobarbituric acid reactive substance), levels of liver transaminases [serum glutamate pyruvate transaminase (sGPT) and serum glutamate oxaloacetate transaminase (sGOT)] and serum lactate dehydrogenase (sLDH) levels. The oral administration of LA to TAM-intoxicated rats, produced significant increases in all of the antioxidant enzymes and GSH concomitant with significant decreases in the levels of liver TBARS, TNF-α, transaminases, and LDH levels. Similarly, the oral administration of LA, as a curative agent, to TAM-intoxicated rats, produced similar changes to those as when LA was used as a protective agent, but to a lesser extent. In addition, it was noted that TAM-intoxicated rats exhibited a degree of DNA fragmentation. LA administration to TAM-intoxicated partially inhibited the DNA fragmentation. Therefore, LA has the ability to scavenge free radicals, prevent DNA fragmentation, reduce liver injury and protect against oxidative stress induced by TAM intoxication. Overall, the use of LA as a protective agent against TAM-induced liver injury is more effective than its use as curative (post-TAM administration) agent.

Key words: tamoxifen, tumour necrosis factor-α, α-lipoic acid, glutathione peroxidase, reduced glutathione, thiobarbituric acid reactive substance, catalase, superoxide dismutase, oxidative stress, DNA fragmentation, liver injury