Coenzyme Q10 protects hepatocytes from ischemia reperfusion-induced apoptosis and oxidative stress via regulation of Bax/Bcl-2/PUMA and Nrf-2/FOXO-3/Sirt-1 signaling pathways.

Abstract

Coenzyme Q10 (CoQ10) is a component of the mitochondrial electron transport chain and regarded as a strong anti-oxidant agent. In this study, we focused on the mechanistic insights involved in the hepato-protective effects of CoQ10 against hepatic ischemia reperfusion (IR) injury. Our results revealed that CoQ10 significantly improved hepatic dysfunctions and oxidative stress caused by IR injury. Interestingly, as compared to IR subjected rat, CoQ10 inhibited apoptosis by marked down-regulation of both Bax and PUMA genes while the level of Bcl-2 gene was significantly increased. Moreover, CoQ10 up-regulated PI3K, Akt and mTOR protein expressions while it inhibited the expression of both GSK-3β and β-catenin. Additionally, CoQ10 restored oxidant/antioxidant balance via marked activated Nrf-2 protein as well as up-regulation of both Sirt-1 and FOXO-3 genes. Moreover, CoQ10 strongly inhibited inflammatory response through down-regulation of NF-κB-p65 and decrease both JAK1 and STAT-3 protein expressions with a subsequent modulating circulating inflammatory cytokines. Furthermore, histopathological analysis showed that CoQ10 remarkably ameliorated the histopathological damage induced by IR injury. Taken together, our results suggested and proved that CoQ10 provided a hepato-protection against hepatic IR injury via inhibition of apoptosis, oxidative stress, inflammation and their closed related pathways.

• Authors: Amany R Mahmoud, Fares E M Ali, Tarek Hamdy Abd-Elhamid, Emad H M Hassanein
• Journal: Tissue & cell (Tissue Cell) Vol. 60 Pg. 1-13 (Oct 2019) ISSN: 1532-3072 [Electronic] Scotland
• PMID: 31582012 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Apoptosis Regulatory Proteins
• BCL2 protein, human
• Bbc3 protein, rat
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Ubiquinone
• coenzyme Q10

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Hepatocytes (metabolism, pathology)
• Liver (physiopathology)
• Male
• Oxidative Stress (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Reperfusion Injury (drug therapy, pathology)
• Signal Transduction (drug effects)
• Ubiquinone (analogs & derivatives, pharmacology)
• bcl-2-Associated X Protein (metabolism)