Change of the Profile of Expression of Adaptive Response Genes in Toxic Hepatitis of Different Etiology

Abstract

Introduction. In Russia, the problem of toxic hepatitis is of great importance and relevance. The etiology of toxic hepatitis (industrial toxicants, drugs, ethanol) and, as a consequence, pathogenesis may have significant differences at the molecular genetic level. The aim of the study was to analyze the expression of genes involved in the response to toxic liver damage of various etiologies. Material and methods. Toxic hepatitis was modulated in male albino mongrel rats weighing 180-200 grams assigned to four groups (control group, carbon tetrachloride, paracetamol, ethanol). After 24 and 72 hours of paracetamol administration, rats were anesthetized and the mRNA levels of the Chek1, Gclc, Gstm1, Gstp1, Gstt1, Nfe2l2, Nqo1, Ripk1 genes in the liver homogenate were examined. Results. As a result of the analysis of the genes expression studied, the expression profile was found TO be differed depending on the etiology of toxic hepatitis. With carbon tetrachloride poisoning, an increase in the expression of the Nqo1 genes (p = 0.001), Gstm1 (p = 0.037) and a decrease in the expression of the Nfe2l2 genes (p = 0.004), Ripk1 (p = 0.004) was observed. With the liver damage by paracetamol and its metabolites, opposite to the expression of the Gstm1 gene (p = 0.001) decreased, and the expression of the Nfe2l2 (p = 0.009), Gclc (p = 0.001), Chek1 (p = 0.011) genes increased. During alcohol intoxication, there were no statistically significant changes in the expression profiles of the genes studied. Conclusion. the results obtained may indicate the involvement of various molecular genetic mechanisms in the process of response to toxic liver damage, depending on the etiology.

Etiology and pathogenesis of non-infectious hepatopathy in cattle under industrial production conditions

“…For example, a known method involves isolating the RNA of the NFE2L2 gene from peripheral venous blood lymphocytes and normalizing the amount of RNA to the endogenous control of GAPDH. [18] Quantitative analysis of NFE2L2 gene RNA and statistical analysis of NFE2L2 gene expression are carried out. When the ratio of NFE2L2 gene expression to GAPDH expression is from -10 to 0, acute toxic hepatitis caused by xenobiotics is diagnosed.…”