AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic...AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in 展开更多
AIM To evaluate the hepatoprotective effect of lycopene(Ly) on non-alcoholic fatty liver disease(NAFLD) in rat. METHODS A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats ...AIM To evaluate the hepatoprotective effect of lycopene(Ly) on non-alcoholic fatty liver disease(NAFLD) in rat. METHODS A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglycerides(TG), total cholesterol(TC) in serum and low density lipoproteincholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), free fatty acid(FFA), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P450(CYP) 2E1 in rat liver were determined by immunohistochemistry analysis.RESULTS A significant decrease was observed in the levels of serum AST(2.07-fold), ALT(2.95-fold), and the blood lipid TG(2.34-fold) and TC(1.66-fold) in the dose of 20 mg/kg Ly-treated rats(P < 0.01), compared to the model group. Pretreatment with 5, 10 and 20 mg/kg of Ly significantly raised the levels of antioxidant enzyme SOD in a dose-dependent manner,to 90.95 ± 9.56, 109.52 ± 11.34 and 121.25 ± 10.68(P < 0.05, P < 0.01), as compared with the model group. Similarly, the levels of GSH were significantly increased(P < 0.05, P < 0.01) after the Ly treatment. Meanwhile, pretreatment with 5, 10 and 20 mg/kg of Ly significantly reduced MDA amount by 30.87, 45.51 and 54.49% in the liver homogenates, respectively(P < 0.01). The Ly treatment group showed significantly decreased levels of lipid products LDL-C(P < 0.05, P < 0.01), improved HDL-C level and significantly decreased content of FFA, compared to the model group(P < 0.05, P < 0.01). Furthermore, the Ly-treated group also exhibited a down-regulated TNF-α and CYP2E1 expression, decreased infiltration of liver fats and reversed histopathological changes, all in a dosedependent manner(P < 0.05, P < 0.01). CONCLUSION This study sugges展开更多
AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the ...AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver 展开更多
AIM： To investigate the hepatoprotective activity of tea polyphenols （TP） and its relation with cytochrome P450 （CYP450） expression in mice. METHODS： Hepatic CYP450 and CYPbs levels were measured by UV-spectroph...AIM： To investigate the hepatoprotective activity of tea polyphenols （TP） and its relation with cytochrome P450 （CYP450） expression in mice. METHODS： Hepatic CYP450 and CYPbs levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP （25, 50 and 100 mg/kg per day）. Then the mice were intragastricly pre-treated with TP （100, 200 and 400 mg/kg per day） for six days before paracetamol （1000 mg/kg） was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP （100, 200, and 400 mg/kg per day） for five days before paracetamol （500 mg/kg） was given. Hepatic CYP2E1 and CYPIA2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. RESULTS： The hepatic CYP450 and CYPb5 levels in mice of TP-treated groups （100, 200 and 400 mg/kg per day） were decreased in a dose-dependent manner compared with those in the negative control mice.TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYPIA2 expression at both protein and mRNA levels in a dose-dependent manner. CONCLUSION： TP possess potential hepatoprotective properties and can suppress CYP450 expression.展开更多
AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducte...AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC),100 cases of chronic gastritis (CG),and 150 controls (C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/Pst1 genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observed,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjects,and the GSTM1 null genotype in Caucasians,while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.展开更多
AIM： To analyze occupational health hazards exposure to doses lower than the Chinese occupational health standard in a selected VC polymerization plant in China, and also to elucidate the relationship between genetic...AIM： To analyze occupational health hazards exposure to doses lower than the Chinese occupational health standard in a selected VC polymerization plant in China, and also to elucidate the relationship between genetic polymorphisms and genetic susceptibility on liver lesions of workers exposed to vinyl chloride monomer （VCM）. METHODS： In order to explore the mechanism of VCM- related health effects, we used a case-control design to investigate the association between the genetic polymorphisms of metabolic enzymes and liver lesions in workers occupationally exposed to VCM. Genotypes of CYP2E1, GSTT1, GSTM1, ALDH2 and ADH2 were identified using PCR and PCR-RFLP. RESULTS： Even when the concentration of VCM was lower than the current Chinese occupational health standard, neurasthenia, pharyngeal irritation, liver ultrasonography abnormalities and hemoglobin disorders were significantly higher in exposure subjects compared to non-exposure subjects, and the relative risks （RRand 95% C1） were 1.74 （1.06-2.85）, 1.97 （1.56-2.48）, 10.69 （4.38-26.12）, and 2.07 （1.20-3.57）. CYP2E1 c1c2/c2c2 genotype was significantly associated with liver damages （OR 3.29, 95% CI 1.51-7.20, P〈0.01）. CONCLUSION： The incidences of neurasthenia and liver ultrasonography abnormalities significantly increase when the cumulative exposure dose increases. The genotypes of metabolic enzymes （CYP2E1 c1c2/c2c2, null GSTT1 and ADH2 1-1） play important roles in VCM metabolism. Polymorphisms of CYP 2E1, GSTT1 and ADH2 may be a major reason of genetic susceptibility in VCM-induced hepatic damage.展开更多
Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic ac...Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.展开更多
AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) w...AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1 *2A, CYP1A1 *2C CYP2E1 *5B and CYP2E1 *6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The EPHX1 Tyr113 His, EPHX1 His139 Arg and CYP1A1 *2C polymorphisms were detected by real-time PCR. Chisquared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05.RESULTS Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, P < 0.01). Male individuals were less susceptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, P < 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P < 0.01), dominant(OR = 2.82, 95%CI: 1.74-4.55, P < 0.01), overdominant(OR = 2.58, 95%CI: 1.59-4.19, P < 0.01), and log-additive models(OR = 2.84, 95%CI: 1.78-4.52, P < 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant(heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P < 0.01; homozygous polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, P < 0.01), dominant(OR = 2.97, 95%CI: 1.97-4.50, P < 0.01), recessive(OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, P < 0.01), and log-additive models(OR = 2.78, 95%CI: 1.91-4.06, P < 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B(C) and CYP2E1*6(A) polymorphisms was associated with SCRC(P = 0.002). However, the CYP1A1 *2A, CYP1A1 *2C, EPHX1 Tyr113 His and EPHX1 His139 Arg polymorphisms were not associated with SCRC.CONCLUSION In conclusion, the results demonstrated that CYP2E1*5B and CYP2E1*6展开更多
BACKGROUND Cholangiocarcinoma(CCA)is an intractable cancer,and its incidence in north eastern Thailand is the highest worldwide.Infection with the liver fluke Opisthorchis viverrini(OV)has been associated with CCA ris...BACKGROUND Cholangiocarcinoma(CCA)is an intractable cancer,and its incidence in north eastern Thailand is the highest worldwide.Infection with the liver fluke Opisthorchis viverrini(OV)has been associated with CCA risk.However,animal experiments have suggested that OV alone does not induce CCA,but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters.Therefore,in humans,other environmental and genetic factors may also be involved.AIM To examine relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes.METHODS This hospital-based case-control study enrolled 95 case-control pairs matched by age(±5 years)and sex.We examined relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes,serum anti-OV,alcohol consumption,and smoking.Polymorphisms of CYP2E1,IL-6(-174 and-634),IL-10(-819),and NF-κB(-94)and their cooccurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed.RESULTS Although CCA risk was not significantly associated with any single polymorphism,persons with the GSTT1 wild-type and CYP2E1 c1/c2+c2/c2 genotype had an increased risk(OR=3.33,95%CI:1.23-9.00)as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype.The presence of anti-OV in serum was associated with a 7-to 11-fold increased risk,and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms.CONCLUSION In addition to infection with OV,gene-gene interactions may be considered as one of the risk factors for CCA development.展开更多
基金Supported by Natural Science Foundation of Fujian Province,China,No.C001009
文摘AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in
文摘AIM To evaluate the hepatoprotective effect of lycopene(Ly) on non-alcoholic fatty liver disease(NAFLD) in rat. METHODS A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglycerides(TG), total cholesterol(TC) in serum and low density lipoproteincholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), free fatty acid(FFA), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P450(CYP) 2E1 in rat liver were determined by immunohistochemistry analysis.RESULTS A significant decrease was observed in the levels of serum AST(2.07-fold), ALT(2.95-fold), and the blood lipid TG(2.34-fold) and TC(1.66-fold) in the dose of 20 mg/kg Ly-treated rats(P < 0.01), compared to the model group. Pretreatment with 5, 10 and 20 mg/kg of Ly significantly raised the levels of antioxidant enzyme SOD in a dose-dependent manner,to 90.95 ± 9.56, 109.52 ± 11.34 and 121.25 ± 10.68(P < 0.05, P < 0.01), as compared with the model group. Similarly, the levels of GSH were significantly increased(P < 0.05, P < 0.01) after the Ly treatment. Meanwhile, pretreatment with 5, 10 and 20 mg/kg of Ly significantly reduced MDA amount by 30.87, 45.51 and 54.49% in the liver homogenates, respectively(P < 0.01). The Ly treatment group showed significantly decreased levels of lipid products LDL-C(P < 0.05, P < 0.01), improved HDL-C level and significantly decreased content of FFA, compared to the model group(P < 0.05, P < 0.01). Furthermore, the Ly-treated group also exhibited a down-regulated TNF-α and CYP2E1 expression, decreased infiltration of liver fats and reversed histopathological changes, all in a dosedependent manner(P < 0.05, P < 0.01). CONCLUSION This study sugges
文摘AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver
基金Grant from the Science Foundation of Educational Department of Liaoning Province,05L117Dalian Science&Technology Bureau,2007J22JH012
文摘AIM： To investigate the hepatoprotective activity of tea polyphenols （TP） and its relation with cytochrome P450 （CYP450） expression in mice. METHODS： Hepatic CYP450 and CYPbs levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP （25, 50 and 100 mg/kg per day）. Then the mice were intragastricly pre-treated with TP （100, 200 and 400 mg/kg per day） for six days before paracetamol （1000 mg/kg） was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP （100, 200, and 400 mg/kg per day） for five days before paracetamol （500 mg/kg） was given. Hepatic CYP2E1 and CYPIA2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. RESULTS： The hepatic CYP450 and CYPb5 levels in mice of TP-treated groups （100, 200 and 400 mg/kg per day） were decreased in a dose-dependent manner compared with those in the negative control mice.TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYPIA2 expression at both protein and mRNA levels in a dose-dependent manner. CONCLUSION： TP possess potential hepatoprotective properties and can suppress CYP450 expression.
文摘AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC),100 cases of chronic gastritis (CG),and 150 controls (C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/Pst1 genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observed,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjects,and the GSTM1 null genotype in Caucasians,while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.
基金Supported by the National Natural Science Foundation of China, No. 30070650 and National Key Basic Research and Development Program of China, No. 2002CB512909
文摘AIM： To analyze occupational health hazards exposure to doses lower than the Chinese occupational health standard in a selected VC polymerization plant in China, and also to elucidate the relationship between genetic polymorphisms and genetic susceptibility on liver lesions of workers exposed to vinyl chloride monomer （VCM）. METHODS： In order to explore the mechanism of VCM- related health effects, we used a case-control design to investigate the association between the genetic polymorphisms of metabolic enzymes and liver lesions in workers occupationally exposed to VCM. Genotypes of CYP2E1, GSTT1, GSTM1, ALDH2 and ADH2 were identified using PCR and PCR-RFLP. RESULTS： Even when the concentration of VCM was lower than the current Chinese occupational health standard, neurasthenia, pharyngeal irritation, liver ultrasonography abnormalities and hemoglobin disorders were significantly higher in exposure subjects compared to non-exposure subjects, and the relative risks （RRand 95% C1） were 1.74 （1.06-2.85）, 1.97 （1.56-2.48）, 10.69 （4.38-26.12）, and 2.07 （1.20-3.57）. CYP2E1 c1c2/c2c2 genotype was significantly associated with liver damages （OR 3.29, 95% CI 1.51-7.20, P〈0.01）. CONCLUSION： The incidences of neurasthenia and liver ultrasonography abnormalities significantly increase when the cumulative exposure dose increases. The genotypes of metabolic enzymes （CYP2E1 c1c2/c2c2, null GSTT1 and ADH2 1-1） play important roles in VCM metabolism. Polymorphisms of CYP 2E1, GSTT1 and ADH2 may be a major reason of genetic susceptibility in VCM-induced hepatic damage.
基金financially supported by National Natural Science Foundation of China(81700524)Natural Science Foundation of Fujian Province(2022J01866)from Fujian Provincial Department of Science and Technology+1 种基金Key Project of Fujian University of Traditional Chinese Medicine(X2021019)Collaborative Innovation and Platform Establishment Project of Department of Science and Technology of Guangdong Province(2019A050520003)。
文摘Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.
基金Supported by Sao Paulo Research Foundation(FAPESP),No.2011/23969-1 and No.2012/02473-0Coordination for the Improvement of Higher Education Personnel(CAPES)(Master grant)and National Council of Technological and Scientific Development(CNPq),No.310582/2014-8
文摘AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1 *2A, CYP1A1 *2C CYP2E1 *5B and CYP2E1 *6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The EPHX1 Tyr113 His, EPHX1 His139 Arg and CYP1A1 *2C polymorphisms were detected by real-time PCR. Chisquared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05.RESULTS Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, P < 0.01). Male individuals were less susceptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, P < 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P < 0.01), dominant(OR = 2.82, 95%CI: 1.74-4.55, P < 0.01), overdominant(OR = 2.58, 95%CI: 1.59-4.19, P < 0.01), and log-additive models(OR = 2.84, 95%CI: 1.78-4.52, P < 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant(heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P < 0.01; homozygous polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, P < 0.01), dominant(OR = 2.97, 95%CI: 1.97-4.50, P < 0.01), recessive(OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, P < 0.01), and log-additive models(OR = 2.78, 95%CI: 1.91-4.06, P < 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B(C) and CYP2E1*6(A) polymorphisms was associated with SCRC(P = 0.002). However, the CYP1A1 *2A, CYP1A1 *2C, EPHX1 Tyr113 His and EPHX1 His139 Arg polymorphisms were not associated with SCRC.CONCLUSION In conclusion, the results demonstrated that CYP2E1*5B and CYP2E1*6
基金Supported by Japan Society for the Promotion of Science,No.21406011.
文摘BACKGROUND Cholangiocarcinoma(CCA)is an intractable cancer,and its incidence in north eastern Thailand is the highest worldwide.Infection with the liver fluke Opisthorchis viverrini(OV)has been associated with CCA risk.However,animal experiments have suggested that OV alone does not induce CCA,but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters.Therefore,in humans,other environmental and genetic factors may also be involved.AIM To examine relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes.METHODS This hospital-based case-control study enrolled 95 case-control pairs matched by age(±5 years)and sex.We examined relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes,serum anti-OV,alcohol consumption,and smoking.Polymorphisms of CYP2E1,IL-6(-174 and-634),IL-10(-819),and NF-κB(-94)and their cooccurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed.RESULTS Although CCA risk was not significantly associated with any single polymorphism,persons with the GSTT1 wild-type and CYP2E1 c1/c2+c2/c2 genotype had an increased risk(OR=3.33,95%CI:1.23-9.00)as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype.The presence of anti-OV in serum was associated with a 7-to 11-fold increased risk,and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms.CONCLUSION In addition to infection with OV,gene-gene interactions may be considered as one of the risk factors for CCA development.
