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Betulinic acid protects against cardiotoxicity of the organophosphorus pesticide chlorpyrifos by suppressing oxidative stress, inflammation, and apoptosis in rats

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Abstract

The widespread application of organophosphorus (OP) pesticides can affect the environment as well as the animal and human health. Chlorpyrifos (CPF) is a broad-spectrum OP pesticide used in agriculture and can cause several toxic effects in which oxidative stresses and inflammation play a key role. This study aimed to evaluate the protective activity of betulinic acid (BA), an antioxidant and anti-inflammatory pentacyclic triterpene, against CPF cardiotoxicity in rats. The rats were divided into four groups. CPF (10 mg/kg) and BA (25 mg/kg) were orally administered for 28 days, and blood and heart samples were collected. CPF-administered rats showed an increase in serum cardiac troponin I (cTnI), creatine kinase (CK)-MB, and lactate dehydrogenase (LDH), accompanied with multiple myocardial tissue alterations. Lipid peroxidation (LPO), nitric oxide (NO), nuclear factor-kappaB (NF-κB), interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were increased, and antioxidant were decrease in CPF-administered rats. BA ameliorated cardiac function markers and tissue injury, decreased LPO, NO, NF-κB, and proinflammatory cytokines, and increased antioxidants. In addition, BA decreased proapoptosis markers, and increased B-cell lymphoma (Bcl)-2, IL-10, Nrf2, and HO-1 in the heart of CPF-treated rats. In conclusion, BA protected against cardiotoxicity in CPF-administered rats by mitigating oxidative stress, inflammation, and apoptosis, and enhanced Nrf2 and antioxidants.

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Acknowledgements

The author thanks Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia, for supporting this work through the Researchers Supporting Project Number (PNURSP2023R381).

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Princess Nourah bint Abdulrahman University Researchers Supporting Project Number (PNURSP2023R381), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

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Correspondence to Reem S. Alruhaimi.

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The experiment was conducted according to the guidelines of the National Institutes of Health (NIH publication No. 85–23, revised 2011) and was approved by the Research Ethics Committee at Princess Nourah bint Abdulrahman University (IRB approval number: HAP-01-R-059).

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Alruhaimi, R.S. Betulinic acid protects against cardiotoxicity of the organophosphorus pesticide chlorpyrifos by suppressing oxidative stress, inflammation, and apoptosis in rats. Environ Sci Pollut Res 30, 51180–51190 (2023). https://doi.org/10.1007/s11356-023-25917-6

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