PM2.5 from diesel exhaust attenuated fisetin mediated cytoprotection in H9c2 cardiomyocytes subjected to ischemia reoxygenation by inducing mitotoxicity.

Abstract

The impact of PM2.5 from diesel exhaust (termed as diesel particulate matter (DPM)) on ischemia re-oxygenation (IR) injury and the consequent effect of fisetin to attenuate this injury remains unclear. IR was induced in H9c2 cells after 24 hrs of fisetin treatment. The cells when incubated with 100 µg/mL of DPM followed by IR, induced 60% cell death which was escalated to 78% with DPM exposure. Fisetin significantly attenuated IR induced cytotoxicity, improved mitochondrial activity and reduced oxidative stress in normal cells but failed to render protection against IR in presence of DPM. Isolated mitochondria experiment confirmed the mitotoxic effect of DPM. Immunoblot analysis established the failure of fisetin to activate PI3K/Akt signaling pathway. Based on the above observations, we concluded that fisetin mediated protection against IR was abrogated with DPM exposure due to augmented mitochondrial dysfunction and inactivation of PI3K/Akt signaling pathway.

• Authors: Bhavana Sivakumar, Gino A Kurian
• Journal: Drug and chemical toxicology (Drug Chem Toxicol) Vol. 46 Issue 1 Pg. 15-23 (Jan 2023) ISSN: 1525-6014 [Electronic] United States
• PMID: 34806509 (Publication Type: Journal Article)

Chemical References

• Vehicle Emissions
• fisetin
• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• Particulate Matter

Topics

• Vehicle Emissions (toxicity)
• Proto-Oncogene Proteins c-akt (metabolism)
• Myocytes, Cardiac
• Cytoprotection
• Phosphatidylinositol 3-Kinases (metabolism, pharmacology)
• Particulate Matter (toxicity, metabolism)