ABSTRACT
AIM:To investigate the effects of dexmedetomidine (DEX) on acute alcoholic hepatic injury in mice and to explore the possible mechanisms .METHODS:Kunming mice (n=50) were randomly divided into 5 groups (n=10):normal saline control (NS) group, acute alcoholic hepatic injury model (E) group, low-dose (10μg/kg) DEX (E+L) group, medium-dose (50 μg/kg) DEX (E+M) group and high-dose (100 μg/kg) DEX (E+H) group.The animals were sacrificed at 6 h after gavage of alcohol or normal saline .The levels of alanine aminotransferase ( ALT) , as-partate aminotransferase (AST), triglyceride (TG), malondialdehyde (MDA), glutathione (GSH) and superoxide dis-mutase ( SOD) were measured .The livers were removed for evaluation of histological characteristics and determining the content of tumor necrosis factor-α( TNF-α) amd interleukin-1β( IL-1β) in the liver tissues by ELISA .The expression levels of cytochrome P4502E1 (CYP2E1) and nuclear factor -κB (NF-κB) in the liver tissues were evaluated by Western blot.RESULTS:Compared with NS group, the levels of ALT, AST and TG were obviously increased in E group , which were obviously decreased in E +M and E+H groups.Compared with NS group, the levels of TNF-α, IL-1βand MDA were obviously increase in E group , which were obviously decreased in E +M and E+H groups.Compared with NS group, the activity of SOD and the content of GSH were obviously decreased in E group , which were obviously increased in E +M and E+H groups.Compared with NS group, the expression of CYP2E1 and NF-κB was obviously increase in E group , which was obviously decreased in E +M and E+H groups.Compared with NS group , ethanol induced marked liver histo- logical injury, which was less pronounced in E +M and E+H groups.CONCLUSION: DEX has a protective effect on mouse liver with acute alcoholic injury by the involvement in the processes of antioxidation and antiinflammation , and its mechanism may be associated with the inhibition of CYP 2E1 and NF-κB expression.
ABSTRACT
AIM:To investigate the effects of dexmedetomidine (DEX) on acute alcoholic hepatic injury in mice and to explore the possible mechanisms .METHODS:Kunming mice (n=50) were randomly divided into 5 groups (n=10):normal saline control (NS) group, acute alcoholic hepatic injury model (E) group, low-dose (10μg/kg) DEX (E+L) group, medium-dose (50 μg/kg) DEX (E+M) group and high-dose (100 μg/kg) DEX (E+H) group.The animals were sacrificed at 6 h after gavage of alcohol or normal saline .The levels of alanine aminotransferase ( ALT) , as-partate aminotransferase (AST), triglyceride (TG), malondialdehyde (MDA), glutathione (GSH) and superoxide dis-mutase ( SOD) were measured .The livers were removed for evaluation of histological characteristics and determining the content of tumor necrosis factor-α( TNF-α) amd interleukin-1β( IL-1β) in the liver tissues by ELISA .The expression levels of cytochrome P4502E1 (CYP2E1) and nuclear factor -κB (NF-κB) in the liver tissues were evaluated by Western blot.RESULTS:Compared with NS group, the levels of ALT, AST and TG were obviously increased in E group , which were obviously decreased in E +M and E+H groups.Compared with NS group, the levels of TNF-α, IL-1βand MDA were obviously increase in E group , which were obviously decreased in E +M and E+H groups.Compared with NS group, the activity of SOD and the content of GSH were obviously decreased in E group , which were obviously increased in E +M and E+H groups.Compared with NS group, the expression of CYP2E1 and NF-κB was obviously increase in E group , which was obviously decreased in E +M and E+H groups.Compared with NS group , ethanol induced marked liver histo- logical injury, which was less pronounced in E +M and E+H groups.CONCLUSION: DEX has a protective effect on mouse liver with acute alcoholic injury by the involvement in the processes of antioxidation and antiinflammation , and its mechanism may be associated with the inhibition of CYP 2E1 and NF-κB expression.
ABSTRACT
The effects of toluene in dimethylformamide (DMF)-induced hepatotoxicity were investigated with respect to the induction of cytochrome P-450 (CYP) and the activities of related enzymes. The rats were treated intraperitoneally with the organic solvents in olive oil (Single treatment groups: 450 [D1], 900 [D2], 1,800 [D3] mg DMF, and 346 mg toluene [T] per kg of body weight; Combined treatment groups: D1+T, D2+T, and D3+T) once a day for three days, while the control group received just the olive oil. Each group consisted of 4 rats. The activities of the xenobiotic metabolic enzymes and the hepatic morphology were assessed. The immunoblots indicated that the expression of CYP2E1 was considerably enhanced depending on the dosage of DMF and the CYP2E1 blot densities were significantly increased after treatment with both DMF and toluene, compared to treatment with DMF alone. The activities of glutathione-S-transferase and glutathione peroxidase were either decreased or remained unaltered after treatment with DMF and toluene, whereas the lipid peroxide levels were increased with increasing dosage of DMF and toluene. The liver tissue in the D3 group (1,800 mg/kg of DMF) showed signs of microvacuolation in the central vein region and a large necrotic zone around the central vein, in rats treated with both DMF (1,800 mg/kg) and toluene (D3T). These results suggest that the expression of CYP2E1 is induced by DMF and enhanced by toluene. These changes may have facilitated the accelerated formation of N-methylformamide (NMF) from toluene, and the generated NMF may directly induce liver damage.
Subject(s)
Animals , Rats , Body Weight , Cytochrome P-450 CYP2E1 , Cytochrome P-450 Enzyme System , Dimethylformamide , Formamides , Glutathione Peroxidase , Lipid Peroxides , Liver , Olea , Plant Oils , Solvents , Toluene , Veins , Olive OilABSTRACT
Objective:To explore the relationship between genetic polymorphism of ALDH2 and CYP2E1 and alcoholic liver disease(ALD) in Han people. Methods:PCR-RFLP was used to detect the frequencies of gene types and allele of ALDH and CYP2E1 in health control group(45 cases),ALD group(48 cases),alcohol dependent group(38 cases) and non-ALD(NALD) group(42 cases),and the frequencies were compared. Results:The difference of the frequencies of ALDH2*1 and ALDH2*2 had statistic significance between health control group and ALD group,and between in ALD group and NALD group(P
ABSTRACT
Objective To investigate the correlation between the CYP2E1 enzymes and alcoholic liver disease.Methods Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method was used to determine polymorphism of CYP2E1.A case control study of 183 subjects was carried out including 40 cases of alcoholic liver disease,40 alcohol dependent group,40 nonalcoholic liver disease and 63 controls.Results The frequency of B genotype or C2 allele gene was significantly higher in alcoholic liver disease than in control(P
ABSTRACT
BACKGROUND: The purpose of this study was to investigate genetic polymorphisms of cytochrome P4502E1 (CYP2E1) among healthy control and alcoholic Koreans in order to determine its relation-ship to the development of alcoholism. We also evaluate the diagnostic usefulness of carbohydrate deficient transferrin (CDT) in alcoholism. METHODS: The healthy control group included 72 males and 32 females. Patients with alcoholism included 53 males and 12 females who met DSM-IV diagnostic criteria (American Psychiatric Asso-ciation, 1994) and were admitted to alcoholism treatment units. Rsa I and Pst I restriction fragment length polymorphisms of CYP2E1 gene PCR product determined the genotype of CYP2E1. The serum level of CDT was analyzed by Behring Nephelometer II using %CDT turbidimetric immunoassay kit. RESULTS: The prevalence of CYP2E1 genotypes was 74.0% for type A, 23.1% for type B, and 2.9% for type C in the 104 healthy subjects, and 93.8% for type A and 6.2% for tyupe B in the 65 patients with alcoholism. The allele frequency of c1 and c2 of CYP2E1 was 85.6% and 14.4%, respectively, in the control group and 96.9% and 3.1%, respectively, in the alcoholics. The %CDT range in healthy controls and alcoholics was 0-7.8% and 3.1-21.1%, respectively. The serum CDT level in the patients with alcoholism (14.4 +/-4.5, mean +/-SD) was higher than that of healthy controls (3.2 +/-1.2, ) (P<0.05). The sensitivity, specificity, positive predictive value, negative predictive value, false positive rate, false negative rate, and test efficiency of %CDT were 85.1%, 93.3%, 88.7%, 90.6%, 6.7%, 15.4%, and 89.9%, respectively. CONCLUSIONS: There was a significant difference in frequencies of CYP2E1 genotype (P=0.001) and allele (P=0.003) between patient with alcoholism and control group, and the absence of CYP2E1 c2 allele was associated with alcoholism. Assessment of CDT yielded useful and objective informa-tion in the diagnosis and identification of alcoholism.