Metabolic and molecular-genetic changes in the liver during carbon tetrachloride intoxication

Abstract

Introduction. Toxic hepatitis (TH) is a complex and multifaceted disease, the development of which is mediated by a complex of biochemical and molecular genetic interactions. The current understanding of the pathogenesis of TH and, as a consequence, its treatment is based on standardization of the phenotype of the disease, often without taking into account metabolic disorders within the cells. Material and methods. experimental studies were performed on white outbred male rats weighing 200-220 g. A 50% solution of TCM was used as a toxicant. Biochemical studies were performed on a laboratory medical photometer “Stat Fax 3300” using clinical test kits and control materials manufactured by Vector-Best LLC. Liver tissue for histological examination was subjected to the standard histological procedure and paraffin embedding. Sections 5-7 μm thick were stained with hematoxylin-eosin. Gene expression analysis was performed using real-time PCR amplification on a RotorGene instrument (QIAGEN). Statistical processing of experimental data was performed using the Pearson correlation coefficient and one-way analysis of variance (ANOVA). The results were considered reliable at p <0.05. Results. As a result of the analysis of the correlation of the expression of the studied genes and the level of biochemical parameters, it was found that the correlation of the expression of the Nfe2l2 and Gstm1 genes was r = 0.812 (p = 0.0001). The dynamics of gene expression of Chek, Gstm1, Gstp1, Nfe2l2, had a negative correlation with the level of AST activity in blood serum. And the expression of the genes Chek, Gclc, Gstm1, Nfe2l2, Ripk, Sod1 with an index of ALT activity in the blood serum. After 72 hours, the expression of almost all of the studied genes became multidirectional. And the correlation between indices is often not determined. An analysis of the relationship between the level of cytolysis enzymes and the correlation level of the studied genes showed that after 72 hours the correlation was observed in the Gstm1, Hmox, and Sod1 genes with the levels of AST and ALT.