Transcriptional activity of glutathione system genes in toxic hepatitis caused by paracetamol

The aim of the study was to study the changes in the transcriptional activity of the GSTM, GSTP and GSTT genes in acute toxic hepatitis caused by paracetamol and against the background of preliminary administration of drugs (heptor, mexidol, oxymethyluracil).

Material and methods: Toxic hepatitis was modulated in male albino mongrel rats assigned to fi ve groups (control group, primed with paracetamol without subsequent administration of the drug, with the administration of heptor, mexidol and oxymethyluracil). After 24 and 72 hours of paracetamol administration, the rats were anesthetized and the mRNA levels of the GSTM, GSTP and GSTT genes in the liver homogenate were examined. Drugs were administered one hour before paracetamol administration.

Results: It has been shown that with 24-hour exposure to paracetamol, the expression ratio of the GSTM gene increased from –0.37 in the control group to 1.03 in the untreated group. After 72 hours of exposure to the toxicant, it was elevated compared with the control group in all groups (paracetamol without treatment — 0.77; heptor — 1.74; mexidol — 1.51; OMU — 1.62). An analysis of the representation of GSTT gene transcripts after 72 hours of exposure showed a stepwise increase and decrease in the expression level in the groups studied. The expression of the GSTP gene with the 24-hour experiment was reduced and ranged from –0.3 to –1.51. (F = 2.916; p = 0.038), and with 72 hours of exposure to paracetamol, the results were opposite. Statistically signifi cant values (p = 0.032) were obtained by comparing the group with paracetamol without treatment and when used as the OMU drug.

Conclusion: the results obtained may indicate the involvement of the given genes in paracetamol metabolism in liver cells. It was found that OMU is a hepatoprotector responsible for restoring the antioxidant defense system. 

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