Specnuezhenide reduces carbon tetrachloride-induced liver injury in mice through inhibition of oxidative stress and hepatocyte apoptosis.

Abstract

OBJECTIVES:

This study aimed to investigate the hepatoprotective effects of specnuezhenide against carbon tetrachloride (CCl4)-induced liver injury in mice.

METHODS:

Male C57BL/6 mice were intraperitoneally injected with 10 ml/kg body weight of CCl4 (0.5% diluted in arachis oil) for acute liver injury after oral administration of specnuezhenide for 7 days. Twenty-four hours after the final CCl4 injection, mice were euthanized and plasma and liver samples were collected.

KEY FINDINGS:

The results showed that specnuezhenide markedly and dose-dependently reduced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity and relative liver weight, as well as ameliorated histopathological damage caused by CCl4 and decreased malondialdehyde (MDA) levels, and increased the activity of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, specnuezhenide promoted the expression and nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the mRNA and protein expression of Nrf2 signalling-related genes heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Finally, TUNEL staining and immunohistochemistry indicated that specnuezhenide prevented CCl4-induced hepatocytic apoptosis by up-regulating B-cell lymphoma 2 (Bcl-2) expression and downregulating Bcl-2-associated X (Bax) expression.

CONCLUSIONS:

Specnuezhenide reduced CCl4-induced liver injury in mice by inhibiting oxidative stress via activation of Nrf2 signalling and decreasing hepatocyte apoptosis.

• Authors: Dongmei Hu, Shaojie Huang, Yi Ding, Xian Zhao, Wei Zhang, Haixia Chen, Jingwen Wang
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 74 Issue 2 Pg. 191-199 (Feb 01 2022) ISSN: 2042-7158 [Electronic] England
• PMID: 34923584 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Glucosides
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Pyrans
• nuezhenide
• Carbon Tetrachloride

Topics

• Animals
• Apoptosis (drug effects)
• Carbon Tetrachloride
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Glucosides (administration & dosage, pharmacology)
• Hepatocytes (drug effects, pathology)
• Liver Diseases (prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• Pyrans (administration & dosage, pharmacology)
• Signal Transduction (drug effects)