Anti-NFE2L2 Monoclonal Antibody

Background. Oxidative stress is extremely important in the pathogenesis of chronic hepatitis C virus (HCV). In response to oxidative stress, adaptive antioxidant defenses are upregulated in the liver. The balance between antioxidant response and oxidative stress plays a key role in hepatic injury in HCV infection. Objectives. The objective of this study was to assess the hepatic expression of the antioxidant genes GFER (growth factor erv1-like) and NQO1 (NAD(P) H: quinone oxidoreductase-1) and the regulatory gene NFE2L2 (nuclear factor erythroid 2-related factor-2) in liver biopsy specimens obtained from chronic HCV patients with regard to selected clinical parameters and histology, and to determine whether GFER and NQO1 expression is dependent on NFE2L2. Material and methods. The study group consisted of 42 patients with chronic HCV. Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the expression of antioxidant and regulatory genes in liver biopsy samples. Results. Positive correlation was observed between the hepatic expression of NFE2L2 and NQO1 in the chronic HCV patients (p < 0.0001). The hepatic expression of NFE2L2 was significantly lower in patients with advanced liver fibrosis (p = 0.05). However, there was no significant difference in the hepatic expression of GFER and NQO1 in relation to the progression of liver steatosis, inflammation and fibrosis. Conclusions. The hepatic expression of NFE2L2 is associated with NQO1 and low stage of hepatic fibrosis in patients infected with HCV.

Susceptibility to adverse drug reactions (ADRs), multimorbidity, and frailty are associated with human aging, yet there is wide variation in the severity and age at which individuals are afflicted. Identifying genetic markers of increased risk of this phenotype would help stratify individuals to specialist interventions. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates a cell's response to stressors, including the expression of enzymes involved in drug metabolism. Its expression has been shown to decline in animal aging models. In this study, we tested the hypothesis that Nrf2 gene (NFE2L2) transcription/translation decline in human aging and that single-nucleotide polymorphisms (SNPs) in the NFE2L2 gene are associated with increased ADR risk, multimorbidity, and frailty in older people. Gene expression and protein levels were measured in peripheral blood mononuclear cells donated from healthy patients aged 18-80 years old. NFE2L2 genotypes were determined at three loci in a subpopulation of patients recruited to the PRIME study (a multicenter prospective cohort study that followed older adults for 8 weeks post-discharge to determine ADR). Both NFE2L2 gene and Nrf2 protein expression declined significantly with age in human peripheral blood mononuclear cells. In the PRIME substudy population, the rs35652124 NFE2L2 SNP was associated with increased ADR risk and decreased frailty and multimorbidity scores.