The effect of chitosan-quercetin complex on the expression of selective genes in NF-κB pathway and TNFR-1 receptor in male wistar rats with non-alcoholic steatohepatitis

Abstract

Non-alcoholic fatty liver disease involves excessive accumulation of fat in the liver. Oxidative stress is involved in the disease progression by various mechanisms, such as activating inflammatory pathways, especially the NF-κB pathway. Quercetin, a substance with antioxidant and anti-inflammatory properties but limited-bioavailability is delivered biologically in various drug formulations. the aim of the present study was to investigate the effect of chitosan-quercetin complex on the expression of selective genes in NF-κB: TNFR-1 pathway in male wistar rats with induced non-alcoholic steatohepatitis. Material and Method: Thirty-seven male Wistar rats were fed a normal or high-fat diet containing high levels of palmitic acid for three months. The last four weeks the patient groups were treated with quercetin/ chitosan or chitosan-quercetin nanoparticles. serum levels of liver enzymes, triglycerides, total cholesterol, serum antioxidant markers, fatty acid composition of liver tissue and the expression of selective genes of NF-κB pathway was examined in the liver. Results: A significant increase in the mRNA expression of TNFR-1, TRADD, IL-6, A20 and MKK7, was induced in the fatty liver group. no significant changes of cIAP1 mRNA levels was observed between groups. In other genes, the treatment with nanoparticles, in the expression of IL-6 gene compared to the quercetin group (P < 0.05) and in the expression of TNF-R1 (P < 0.05) and MKK7 compared to the chitosan group (P < 0.01) caused further reduction. Increase in linoleate (P < 0.01) and γ-linolenate (P < 0.05) and decrease in palmitate, stearate, pentadcanoate and heptadecanoate (P < 0.05) were mainly observed in the quercetin and nanoparticle groups. Decreases in AST, TG, T-chol, and increases in TAC occurred in all three groups (P < 0.05), although nanoparticle treatment performed best for lipid markers (P < 0.001) and TAC(P < 0.01).