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Isorhamnetin Protects Against Organophosphate-Induced Cardiac Damage in Wistar Rats Through Redox Balance and
Yousra Bseiso1, Badriyah S Alotaibi2, Alaa A A Aljabali3
1Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa, Jordan.
Basic & Clinical Pharmacology & Toxicology
|February 25, 2026
Summary
Isorhamnetin protects against chlorpyrifos-induced heart damage by reducing oxidative stress and inflammation. This study shows isorhamnetin can mitigate cardiotoxicity by modulating key signaling pathways.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Chlorpyrifos (CPF) exposure is linked to cardiotoxicity, driven by oxidative stress, inflammation, and apoptosis.
- Isorhamnetin, a potent flavonol, is investigated for its potential cardioprotective effects against CPF-induced myocardial injury.
Purpose of the Study:
- To investigate the protective role of isorhamnetin against chlorpyrifos-induced cardiotoxicity in male Wistar rats.
- To elucidate the underlying mechanisms involving oxidative stress, inflammation, apoptosis, and Nrf2/HO-1 signaling.
Main Methods:
- Rats were assigned to control, isorhamnetin, CPF, or CPF + isorhamnetin groups.
- Evaluated cardiac biomarkers, oxidative/antioxidant status, inflammatory and apoptotic mediators.
- Assessed histopathology and Nrf2/HO-1 signaling pathway activation.
Main Results:
- CPF significantly elevated cardiac biomarkers, oxidative stress markers (TBARS, NO), and inflammatory cytokines (NF-κB p65, TNF-α, IL-6, IL-1β), while decreasing antioxidants (GSH, SOD, catalase, GPx) and IL-10.
- CPF induced apoptosis (increased Bax, caspase-3; decreased Bcl-2) and downregulated Nrf2/HO-1 signaling, causing histopathological damage.
- Isorhamnetin cotreatment significantly reversed these CPF-induced detrimental effects, restoring biochemical and histological parameters and activating Nrf2/HO-1 signaling.
Conclusions:
- Isorhamnetin effectively alleviates chlorpyrifos-induced cardiotoxicity.
- The cardioprotective mechanism involves restoring redox balance and modulating inflammatory and apoptotic pathways.
- Activation of the Nrf2/HO-1 signaling pathway is crucial for isorhamnetin's protective effects.

