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
• Antioxidants pharmacology   metabolism   MeSH
• Galactosamine * toxicity   MeSH
• Liver metabolism   MeSH
• Rats MeSH
• Chemical and Drug Induced Liver Injury * prevention & control   metabolism   MeSH
• Lipopolysaccharides metabolism   MeSH
• Rats, Wistar MeSH
• Signal Transduction MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants MeSH
• Galactosamine * MeSH
• Lipopolysaccharides MeSH
• shogaol MeSH Browser

Acute liver failure (ALF) is a clinical syndrome with high mortality rate, resulting from widespread hepatocyte damage. Its pathophysiological background is still poorly understood and preclinical studies evaluating pathophysiology and new potential therapeutic measures are needed. The model of ALF induced by administration of thioacetamide (TAA) in Lewis rats is recommended as optimal; however, the limitation of previous studies was that they were performed predominantly in male rats. In view of the growing recognition that sex as a biological variable should be taken into consideration in preclinical research, we examined its role in the development of TAA-induced ALF in Lewis rats. We found that, first, intact male Lewis rats showed lower survival rate than their female counterparts, due to augmented liver injury documented by higher plasma ammonia, and bilirubin levels and alanine aminotransferase activity. Second, in female rats castration did not alter the course of TAA-induced ALF whereas in the male gonadectomy improved the survival rate and attenuated liver injury, reducing it to levels observed in their female counterparts. In conclusion, we found that Lewis rats show a remarkable sexual dimorphism with respect to TAA-induced ALF, and male rats display dramatically poorer prognosis as compared with the females. We showed that testosterone is responsible for the deterioration of the course of TAA-induced ALF in male rats. In most general terms, our findings indicate that in the preclinical studies of the pathophysiology and treatment of ALF (at least of the TAA-induced form) the sex-linked differences should be seriously considered.

• MeSH
• Liver Failure, Acute chemically induced   metabolism   pathology   MeSH
• Carcinogens toxicity   MeSH
• Rats MeSH
• Disease Models, Animal MeSH
• Rats, Inbred Lew MeSH
• Sex Factors MeSH
• Testosterone metabolism   MeSH
• Thioacetamide toxicity   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Carcinogens MeSH
• Testosterone MeSH
• Thioacetamide MeSH