Abstract
Doxorubicin (DOX), a widely used chemotherapy, extends its impact beyond cancer cells, notably affecting the heart, leading to substantial concerns about DOX-induced cardiotoxicity (DIC). However, subclinical DIC remains unresolved, necessitating advanced cardio-protection strategies in cancer therapy. Recent research explores carvacrol (CAR), a natural substance with antioxidant and anti-inflammatory properties, as a potential shield against DIC. However, further exploration is warranted, particularly concerning hypertrophy and cardiac fibrosis. This study investigated CAR’s potential cardioprotective properties against DIC in H9c2 cardiomyocytes and rats. Induction with DOX reduced cardiomyocyte viability, while pretreatment with 0.01 µg/mL CAR enhanced the viability of DOX-induced cardiomyocytes. Meanwhile, administration of DOX induced adverse effects in rats, causing decreased total heart weight and left ventricular mass, and lowered blood pressure. DOX also caused cardiac dysfunction, lipid peroxidation, hypertrophy, and fibrosis. In rat models, CAR pretreatment effectively mitigated DOX-induced reductions in blood pressure, hypertrophy, and cardiac fibrosis. However, the pretreatment kept the heart function, oxidative stress, and antioxidant enzymes unaltered. In conclusion, the results show that CAR could be an adjuvant to reduce DIC by ameliorating cardiac fibrosis and hypertrophy.