Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and...

Area of Science:

• Toxicology
• Molecular Biology
• Cell Biology

Background:

• Quinocetone (QCT), a quinoxaline 1,4-di-N-oxide (QdNO), exhibits genotoxicity and hepatotoxicity.
• The precise molecular mechanisms underlying QCT's toxicity remain unclear.
• Investigating protective agents against QdNOs-induced cellular damage is crucial.

Purpose of the Study:

• To investigate the protective effects of quercetin against QCT-induced cytotoxicity.
• To elucidate the molecular mechanisms involved in quercetin's protective action.
• To evaluate quercetin as a potential therapeutic agent against QdNOs toxicity.

Main Methods:

• Human L02 and HepG2 cells were treated with QCT and varying concentrations of quercetin.
• Cell viability, oxidative damage, mitochondrial membrane potential, and apoptosis markers were assessed.
• Western blotting was used to analyze protein expression, including p38, Nrf2, HO-1, CytC, Bax, and Bcl-2.
• Pharmacological inhibitors of p38 and Nrf2 pathways were employed to dissect the underlying mechanisms.

Main Results:

• Quercetin significantly ameliorated QCT-induced cytotoxicity and oxidative stress in liver cells.
• Quercetin treatment inhibited QCT-induced mitochondrial dysfunction, apoptosis, and caspase activation.
• Quercetin upregulated the phosphorylation of p38, Nrf2, and HO-1, indicating activation of this protective pathway.
• Inhibition of p38 or Nrf2 pathways abolished or reduced quercetin's protective effects against QCT.

Conclusions:

• Quercetin demonstrates significant protective effects against QCT-induced cytotoxicity and apoptosis in human liver cells.
• The protective mechanism involves the activation of the p38/Nrf2/HO-1 signaling pathway.
• Quercetin inhibits the ROS/mitochondrial apoptotic pathway, thereby preventing cell death.
• Quercetin shows promise as a preventative agent against QdNOs-induced toxicity in humans and animals.