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.