Effect of grapefruit juice on CYP2E1 gene expression in obese and control rats

Background and Aims: The CYP2E1 gene encodes cytochrome P450 enzymes that play an essential role in liver fat metabolism. Additionally, grapefruit reduces plasma lipids in the body. Therefore, herbal medicines can be considered as an important treatment strategy. The present study aimed to evaluate the effect of grapefruit juice on CYP2E1 gene expression in obese and control rats. Materials and Methods: This experimental study was performed on 24 male Wistar rats weighing 180±20 g. Rats were divided into four groups: control (no treatment), high-fat diet group, treatment group 1 (high cholesterol diet with grapefruit juice 4 ml/kg), and treatment group 2 (high-fat diet with grapefruit juice) (8 ml/kg). They also gavaged for 6 weeks and CYP2E1 gene expression was finally determined. Statistical analyzes were performed using SPSS software (version 22). Results: The results of CYP2E1 gene expression indicated that grapefruit juice at a dose of 8 ml/kg can further reduce the expression of CYP2E1 gene in rats with fatty liver (1.09 ±0.038) than the dose of 4 ml/kg (1.27 ±0.24). This reduction in expression was statistically significant compared to that of the high-fat diet group (3.61 ±0.25) (P=0.003). Conclusion: The results of this study demonstrated that grapefruit juice reduces the expression of the CYP2E1 gene in obese rats due to naringin and recovers the disease by reducing the accumulation of triglycerides in the liver. Therefore, grapefruit juice can be considered as a therapeutic target in fatty liver disease and obesity.

Genetic Variants of Alcohol Metabolizing Enzymes and Alcohol-Related Liver Cirrhosis Risk

Alcohol-related liver disease (ARLD) is a major public health issue caused by excessive alcohol consumption. ARLD encompasses a wide range of chronic liver lesions, alcohol-related liver cirrhosis being the most severe and harmful state. Variations in the genes encoding the enzymes, which play an active role in ethanol metabolism, might influence alcohol exposure and hence be considered as risk factors of developing cirrhosis. We conducted a case-control study in which 164 alcohol-related liver cirrhosis patients and 272 healthy controls were genotyped for the following functional single nucleotide variations (SNVs): ADH1B gene, rs1229984, rs1041969, rs6413413, and rs2066702; ADH1C gene, rs35385902, rs283413, rs34195308, rs1693482, and rs35719513; CYP2E1 gene, rs3813867. Furthermore, copy number variations (CNVs) for ADH1A, ADH1B, ADH1C, and CYP2E1 genes were analyzed. A significant protective association with the risk of developing alcohol-related liver cirrhosis was observed between the mutant alleles of SNVs ADH1B rs1229984 (Pcvalue = 0.037) and ADH1C rs283413 (Pc value = 0.037). We identified CNVs in all genes studied, ADH1A gene deletions being more common in alcohol-related liver cirrhosis patients than in control subjects, although the association lost statistical significance after multivariate analyses. Our findings support that susceptibility to alcohol-related liver cirrhosis is related to variations in alcohol metabolism genes.

Synonymous mutation rs2515641 affects CYP2E1 mRNA and protein expression and susceptibility to drug-induced liver injury

Aim: To evaluate whether the synonymous mutant rs2515641 could affect cytochrome P450 2E1 ( CYP2E1) expression and the response to acetaminophen (APAP) or triptolide (TP) treatment. Materials & methods: HepG2 cells were transfected with lentiviral vector containing either CYP2E1-1263C or CYP2E1-1263T. Some of these recombinant cells were then treated with APAP or TP. CYP2E1 gene expression was detected by PCR and western blot. Results: CYP2E1 gene expression decreased significantly both in mRNA and protein level after rs2515641 mutation, indicating that this polymorphism can affect both transcription and translation. Furthermore, rs2515641 mutation dramatically changes the response of CYP2E1 expression to APAP or TP treatment. Conclusion: Rs2515641 significantly changes CYP2E1 expression and function, which would be expected to affect drug disposition and response.

COMPARISON OF POLYMORPHISM rs2070672 CYP2E1 GENE PROPORTION IN EARLY AND ADVANCED STAGE OF UNDIFFERENTIATED TYPE NASOPHARYNGEAL CARCINOMA IN BALINESE

Introduction: Nasopharyngeal carcinoma is the most common malignancy in the ENT field. The cause of nasopharyngeal carcinoma is multifactorial. One of the risk factors for an increase in nasopharyngeal carcinoma is the rs2070672 polymorphism of the CYP2E1gene. Purpose: To determine the rs2070672 CYP2E1gene polymorphism proportion in early and advanced stage undifferentiated type NPC subjects in Balinese. Method: This research is a cross sectional comparative study. The case population were all subjects with undifferentiated type NPC in the ENT outpatient clinic at Sanglah General Hospital Denpasar. This study uses 65 samples. Data collected in the form of subject characteristics and rs2070672 CYP2E1gene polymorphisms which examined by ARMS-PCR technique. Results: The average age of the sample was 48.1 years, the most were male as many as 48 subjects (73.8%), and the highest was advanced stage as many as 56 subjects (86.2%). In the chi square test the proportion of polymorphisms in the advanced stage was 2.357 times higher than the early stages. The results of multivariate analysis using logistic regression proved that the rs2070672 CYP2E1gene polymorphism at advanced stage was 7.469 times higher than early stage. Conclusion: There is a difference in the proportion of rs2070672 CYP2E1gene polymorphism in undifferentiated type NPC of Balinese, where advanced stage is higher than early stage.