| 1 | Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats显示文摘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 group.Rats 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 wk.Animals 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 wk.Rats 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 oil.Animals in group 5(DENA-carnitine depleted group)received the same treatment as group 3 and group 4.Rats in group 6 (DENA-carnitine supplemented group)received the same treatment as group 2 and group 4.RESULTS: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 tissues.In 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 tissues.Interestingly, 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 values.Histopathological examination of liver tissues confirmed the biochemical data,where L-carnitine prevented DENA-induced hepatic carcinogenesis while D-carnitine-mildronate aggravated DENA-induced hepatic damage. CONCLUSION:Data from this study suggest for the first time that:(1)carnitine deficiency is a risk factor and should be viewed as a mechanism in DENA- induced hepatic carcinogenesis;(2)oxidative stress plays an important role but is not the only cause of DENA-induced hepatic carcinogenesis;and(3) long-term L-carnitine supplementation prevents the development of DENA-induced liver cancer. | 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 | 2009 | World Journal of Gastroenterology2009，15，11： | 4 |
| 2 | Sinapic acid ameliorates D-galactosamine/lipopolysaccharideinduced fulminant hepatitis in rats:Role of nuclear factor erythroidrelated factor 2/heme oxygenase-1 pathways显示文摘BACKGROUND Sinapic acid(SA)has been shown to have various pharmacological properties such as antioxidant,antifibrotic,anti-inflammatory,and anticancer activities.Its mechanism of action is dependent upon its ability to curb free radical production and protect against oxidative stress-induced tissue injuries.AIM To study the hepatoprotective effects of SA against lipopolysaccharide(LPS)/Dgalactosamine(D-GalN)-induced acute liver failure(ALF)in rats.METHODS Experimental ALF was induced with an intraperitoneal(i.p.)administration of 8μg LPS and 800 mg/kg D-GalN in normal saline.SA was administered orally once daily starting 7 d before LPS/D-GalN treatment.RESULTS Data showed that SA ameliorates acute liver dysfunction,decreases serum levels of alanine transaminase(ALT),and aspartate aminotransferase(AST),as well as malondialdehyde(MDA)and NO levels in ALF model rats.However,pretreatment with SA(20 mg/kg and 40 mg/kg)reduced nuclear factor kappalight-chain-enhancer of activated B cells(NF-κB)activation and levels of inflammatory cytokines(tumor necrosis factor-αand interleukin 6).Also,SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.CONCLUSION In conclusion,SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB. | Mushtaq Ahmad Ansari Mohammad Raish Yousef A Bin Jardan Ajaz Ahmad Mudassar Shahid SheikhFayaz Ahmad Nazrul Haq Mohammad Rashid Khan Saleh A Bakheet | 2021 | World Journal of Gastroenterology2021，27，7： | 2 |
您所在的机构暂未开通此部分的功能，请联系管理员