Protective effects of α-Pinene against carbon tetrachloride-induced cardiac injury in Wistar rats: modulation of antioxidant and inflammatory responses

Abstract

The escalating global burden of cardiovascular diseases is a growing concern. Numerous research studies have established that plant-derived polyphenols, including α-pinene—a monocyclic monoterpene found in various plant essential oils—have significant effects on key cardiovascular mechanisms. These effects are mediated through their influence on antioxidant systems, cellular signaling pathways, and gene transcription processes. This study investigated the protective effects of α-pinene against cardiac damage caused by carbon tetrachloride (CCl₄) in Wistar rats. Rats were divided into four groups: a control group receiving saline, a disease control group-administered CCl₄ (1 mL/kg body weight, intraperitoneally), and two treatment groups receiving α-pinene orally at doses of 50 mg/kg and 100 mg/kg body weight alongside CCl₄, to assess its dose-dependent effects. We conducted comprehensive evaluations, including assessments of serum and cardiac toxicity biomarkers, inflammatory mediators, antioxidant defense mechanisms, lipid peroxidation levels, lipid profiles, and histopathological analyses. CCl₄ exposure resulted in notable increases in free fatty acids (FFA), total cholesterol (TC), triglycerides (TG), phospholipids (PL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels, and a decrease in high-density lipoprotein (HDL) levels. Treatment with α-pinene at 100 mg/kg effectively counteracted these lipid profile changes. CCl₄ also caused lipid oxidation and a reduction in antioxidant activities, which were restored to normal levels with α-pinene treatment at 100 mg/kg body weight. Moreover, an upsurge in inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (Hs-CRP)) and cardiac toxicity biomarkers (creatine kinase (CK), and creatine kinase-myocardial band (CK-MB) and troponin) induced by CCl₄ intoxication was reversed by α-pinene. Histopathological studies further validated these findings. The study concludes that α-pinene, administered at a dosage of 100 mg/kg body weight, effectively alleviates cardiac injury induced by CCl₄. The data suggest that α-pinene exerts its protective effects through modulation of various signaling pathways involved in CCl₄-induced cardiac toxicity.