This analysis aims to see whether 6-shogaol could protect rats against D-galactosamine (D-GalN)-induced Hepatotoxicity. The Wistar rats were divided into four groups (n=6). Group 1 received a standard diet, Group 2 received an oral administration of 6-shogaol (20 mg/kg b.wt), Group 3 received an intraperitoneal injection of D-GalN (400 mg/kg b.wt) on 21st day, and Group 4 received an oral administration of 6-shogaol (20mg/kg b.wt) for 21 days and D-GalN (400 mg/kg b.wt) injection only on 21st day. The hepatic marker enzymes activity, lipid peroxidative markers level increased significantly and antioxidant activity/level significantly reduced in D-GalN-induced rats. 6-shogaol Pretreatment effectively improves the above changes in D-GalN-induced rats. Further, inflammatory marker expression and MAPK signaling molecules were downregulated by 6-shogaol. These findings showed that 6-shogaol exerts hepatoprotective effects via the enhanced antioxidant system and attenuated the inflammation and MAPK signaling pathway in D-GalN-induced rats.

• MeSH
• antioxidancia farmakologie   metabolismus   MeSH
• galaktosamin * toxicita   MeSH
• játra metabolismus   MeSH
• krysa rodu Rattus MeSH
• lékové postižení jater * prevence a kontrola   metabolismus   MeSH
• lipopolysacharidy metabolismus   MeSH
• potkani Wistar MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• galaktosamin * MeSH
• lipopolysacharidy MeSH
• shogaol MeSH Prohlížeč

Challenges with various TLR ligands (TLRLs)in combination with D-galactosamine (GalN) in rodents may mimic diverse conditions of acute inflammation and organ failure. Here, we report that CpG (ODN1826, TLR9 agonist)/GalN induced a liver-specific injury with modest systemic effects, whereas R848 (resiquimod, TLR7/8 agonist)/GalN exhibited systemic and liver toxicity. We also observed the protective effect of Gr-1+ cells (the population containing neutrophils) against liver injury in both the R848/GalN and CpG/GalN models. In cytokine measurements, the intraperitoneal administration of antibodies showed a non-specific tolerance induction effect, which was more pronounced in the CpG/GalN than in the R848/GalN model. Cytokine analyses also suggested that the TLR9 agonist/GalN induced a limited degree of systemic inflammation compared to TLR7/8 agonist/GalN models. The relevance of this finding to the TLR9-mediated induction of stress tolerance (protective effect) in non-immune cells is discussed.

• MeSH
• galaktosamin toxicita   MeSH
• imidazoly toxicita   MeSH
• lékové postižení jater etiologie   metabolismus   patologie   MeSH
• lipopolysacharidy toxicita   MeSH
• membránové glykoproteiny agonisté   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• stupeň závažnosti nemoci MeSH
• toll-like receptor 7 agonisté   MeSH
• toll-like receptor 8 agonisté   MeSH
• toll-like receptor 9 agonisté   MeSH
• zánět chemicky indukované   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• galaktosamin MeSH
• imidazoly MeSH
• lipopolysacharidy MeSH
• membránové glykoproteiny MeSH
• resiquimod MeSH Prohlížeč
• Tlr7 protein, mouse MeSH Prohlížeč
• TLR8 protein, mouse MeSH Prohlížeč
• Tlr9 protein, mouse MeSH Prohlížeč
• toll-like receptor 7 MeSH
• toll-like receptor 8 MeSH
• toll-like receptor 9 MeSH

This article is directed at highlighting the involvement of the endogenous stress sensor SIRT1 (silent information regulator T1) as a possible factor involved in hepatoprotection. The selective SIRT1 modulators whether activators (STACs) or inhibitors are being tried experimentally and clinically. We discuss the modulation of SIRT1 on cytoprotection or even cytotoxicity in the liver chemically injured by hepatotoxic agents in rats, to shed light on the crosstalk between SIRT1 and its modulators. A combination of D-galactosamine and lipopolysaccharide (D-GalN/LPS) downregulated SIRT1 expression, while SIRT1 activators, SRT1720, resveratrol, and quercetin, upregulated SIRT1 and alleviated D-GalN/LPS-induced acute hepatotoxicity. Liver injury markers exhibited an inverse relationship with SIRT1 expression. However, under subchronic hepatotoxicity, quercetin decreased the significant increase in SIRT1 expression to lower levels which are still higher than normal ones and mitigated the liver-damaging effects of carbon tetrachloride. Each of these STACs was hepatoprotective and returned the conventional antioxidant enzymes to the baseline. Polyphenols tend to fine-tune SIRT1 expression towards normal in the liver of intoxicated rats in both acute and subchronic studies. Together, all these events give an impression that the cytoprotective effects of SIRT1 are exhibited within a definite range of expression. The catalytic activity of SIRT1 is important in the hepatoprotective effects of polyphenols where SIRT1 inhibitors block and the allosteric SIRT1 activators mimic the hepatoprotective effects of polyphenols. Our findings indicate that the pharmacologic modulation of SIRT1 could represent both an important move in alleviating hepatic insults and a future major step in the treatment of xenobiotic-induced hepatotoxicity.

• MeSH
• lékové postižení jater farmakoterapie   enzymologie   MeSH
• lidé MeSH
• polyfenoly farmakologie   MeSH
• sirtuin 1 antagonisté a inhibitory   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• polyfenoly MeSH
• sirtuin 1 MeSH