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Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats

World Journal of Gastroenterology 2009年第11期15卷 1373-1380页

作者： Salim S Al-Rejaie Abdulaziz M Aleisa Abdulaziz A Al-Yahya Saleh A Bakheet Abdulmalik Alsheikh Amal G Fatani Othman A Al-Shabanah Mohamed M Sayed-Ahmed Department of Pharmacology College of PharmacyKing Saud UniversityPO Box 2457Kingdom of Saudi Arabia Department of Pathology College of MedicineKing Saud UniversityPO Box 2457 Kingdom of Saudi Arabia

AIM:To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis. METHODS:A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each *** in group 1(control group)received a single intraperitoneal(i.p.)injection of normal saline. Animals in group 2(carnitine-supplemented group) were given L-carnitine(200 mg/kg per day)in drinking water for 8 *** in group 3(carnitine-depleted group)were given D-carnitine(200 mg/kg per day)and mildronate(200 mg/kg per day)in drinking water for 8 *** in group 4(DENA group)were injected with a single dose of DENA(200 mg/kg,i.p.)and 2 wk later received a single dose of carbon tetrachloride(2 mL/kg) by gavage as 1:1 dilution in corn *** in group 5(DENA-carnitine depleted group)received the same treatment as group 3 and group *** in group 6 (DENA-carnitine supplemented group)received the same treatment as group 2 and group ***:Administration of DENA resulted in a significant increase in alanine transaminase(ALT), gamma-glutamyl transferase(G-GT),alkaline phosphatase(ALP),total bilirubin,thiobarbituric acid reactive substances(TBARS)and total nitrate/ nitrite(NOx)and a significant decrease in reduced glutathione(GSH),glutathione peroxidase(GSHPx), catalase(CAT)and total carnitine content in liver *** the carnitine-depleted rat model,DENA induced a dramatic increase in serum ALT,G-GT,ALP and total bilirubin,as well as a progressive reduction in total carnitine content in liver ***, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes,TBARS and NOx,and a decrease in total carnitine,GSH,GSHPx, and CAT induced by DENA,compared with the control *** examination of liver tissues confirmed the biochemical data,where L-carnitine prevented DENA-induced hepatic carcinogenesis while D-carnitine-mildronate aggravated DENA-

关键词： Carnitine deficiency D-carnitine L-carnitine Diethylnitrosamine hepatic carcinogenesis

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