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.

Unveiling the Hub Genes Associated with Manganese-Induced Hepatotoxicity

“…In this study, the DEGs in the livers between treated with and without MnCl 2 on the 1st and 3rd day were involved in MAPK signaling pathway (Fig. 3A-B), which was consistent with previous observations [41][42][43]. Li et al (2021) found that LPS could cause the liver damage, and MAPK signaling pathways might be involved in LPS-induced hepatotoxicity in geese [41].…”

“…3A-B), which was consistent with previous observations [41][42][43]. Li et al (2021) found that LPS could cause the liver damage, and MAPK signaling pathways might be involved in LPS-induced hepatotoxicity in geese [41]. In addition, it may also be associated with ALI, and effective inhibition of the MAPK signaling pathway may be critical in protecting the liver from CCl 4 -induced ALI [42].…”

“…Li et al (2021) found that LPS could cause the liver damage, and MAPK signaling pathways might be involved in LPS-induced hepatotoxicity in geese [41]. In addition, it may also be associated with ALI, and effective inhibition of the MAPK signaling pathway may be critical in protecting the liver from CCl 4 -induced ALI [42]. Similarly, MAPK signaling pathway participated in advanced glycation end-products-induced liver damages and oxidative stress.…”

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“…The fibrosis produced in this way bears some resemblance to the mechanisms of hepatic fibrosis in humans (Crespo Yanguas et al, 2016). The first sign of liver injury and fibrosis, is the cellular release of liver enzymes which significantly increased within a short time (Li et al, 2021). According to our findings, inflammatory markers such as TNF-α significantly increase levels of liver enzymes like ALT and AST, which in turn caused an increase in the synthesis of collagen fibers within injured liver cells (Abdelghffar et al, 2022).…”

Anti-Inflammatory Effect of Columbianadin against D-Galactose-Induced Liver Injury In Vivo via the JAK2/STAT3 and JAK2/p38/NF-κB Pathways

“…The MAPK protein family is activated via the phosphorylation of these proteins, which further activate transcription factors regulating the expression of target genes in the nucleus. In a previous study, urantide inhibited liver injury in vivo by inhibiting the MAPK signaling pathway [ 29 ]. In our study, the model group presented higher levels of phosphorylated JAK2 and phosphorylated p38 ( Figure 5 ), indicating the MAPK signaling pathway’s involvement in D-Gal-induced liver injury in vivo.…”