Urantide prevents CCl4‑induced acute liver injury in rats by regulating the MAPK signalling pathway

Abstract

A number of drugs and other triggers can cause acute liver injury (ALI) in clinical practice. Therefore, identifying a safe drug for the prevention of liver injury is important. The aim of the present study was to investigate the potential preventive effect and regulatory mechanism of urantide on carbon tetrachloride (CCl_⁴)‑induced ALI by investigating the expression of components of the MAPK signalling pathway and the urotensin II (UII)/urotensin receptor (UT) system. Liver oedema and severe fatty degeneration of the cytoplasm were observed in ALI model rats, and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were found to be significantly increased. Compared with those in the ALI model group, ALT and AST levels and the liver index did not significantly increase in each group given the preventive administration of urantide, and the liver tissue morphology was correspondingly protected. Moreover, the gene and protein expression levels of UII, G protein‑coupled receptor (GPR14) and the oxidative stress‑sensitive cytokines, α‑smooth muscle actin and osteopontin were decreased, indicating that the protein translation process was effectively maintained. However, the expression levels of MAPK signalling pathway‑related proteins and genes were decreased. It was found that urantide could effectively block the MAPK signalling pathway by antagonizing the UII/UT system, thus protecting the livers of ALI model rats. Therefore, it was suggested that ALI may be associated with the MAPK signalling pathway, and effective inhibition of the MAPK signalling pathway may be critical in protecting the liver.

Keywords: MAPK signalling pathway; acute liver injury; urantide; urotensin II/urotensin receptor system.