Thyme oil and thymol abrogate doxorubicin-induced nephrotoxicity and cardiotoxicity in Wistar rats via repression of oxidative stress and enhancement of antioxidant defense mechanisms

This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin (DOX)-induced renotoxicity, cardiotoxicity, and oxidative stress in Wistar rats. Thyme oil was subjected to GC-MS analysis, which indicated that thymol was the major constituent representing 33.896%. Rats intraperitoneally injected with DOX at a dose of 2 mg/kg b.w./one per week for 7 weeks were co-treated with thyme oil and its major constituent, thymol, at doses 250 and 100 mg/kg b.w./every other day, respectively, by oral gavage for the same period. Thyme oil and thymol markedly ameliorated the raised levels of serum urea, uric acid, and creatinine in DOX-administered rats. They also reduced the elevated activities of serum CK-MB and LDII. Thyme oil was more effective than thymol in decreasing the elevated serum creatinine level and serum CK-MB activity in DOX-administered rats, thereby reflecting its more potent effect on kidney and heart functions. Lipid peroxidation significantly decreased while GSH level and GST and GPx activities significantly increased in kidney and heart of DOX-administered rats treated with thyme oil and thymol. The DOX-induced perturbed kidney histological changes including congestion of glomerulus tuft, inflammatory cells infiltration, protein cast in lumina of the renal tubule, and thickening of the parietal layer of Bowman's capsule were remarkably ameliorated as a result of treatment with thyme oil and thymol; thyme oil was more effective. In addition, DOX-induced deleterious heart histological alterations, including intramuscular infiltration of inflammatory cells, focal necrosis of cardiac myocytes, and edema, were remarkably reduced by treatment with thyme oil and thymol. Thus, it can be concluded that DOX could induce marked toxicity in kidney and heart, and the treatment with thyme oil or thymol produced potential improvement of kidney and heart function and histological integrity via repression of oxidative stress and enhancement of antioxidant defense mechanisms.