Therapeutic Effect of Parthenolide on Paclitaxel-Induced Cardiotoxicity in Rats

The aim of this study was to investigate the therapeutic effects of parthenolide (PTL), the active constituent of Tanacetum parthenium, on paclitaxel (PTX)-induced cardiotoxicity at both gene and protein expression levels. 48 male Sprague-Dawley rats were divided into 6 groups. While no intervention was performed in the control group, the second group received 8 mg/kg PTX. The third group was administered dimethyl sulfoxide (DMSO) as the vehicle control, whereas the fourth, fifth, and sixth groups were treated with 1, 2, and 4 mg/kg PTL, respectively, following PTX administration. The results demonstrated that oxidative stress biomarkers, including glutathione (GSH) and malondialdehyde (MDA), were significantly altered following PTX treatment, indicating oxidative damage; however, PTL administration restored these levels to physiological ranges. Histopathological analyses revealed that PTX caused pathological alterations in cardiac tissue, such as hemorrhage and mononuclear cell infiltration, whereas PTL treatment substantially ameliorated these histopathological lesions. Additionally, 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, indicative of DNA damage, as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels, markers of inflammation, were significantly elevated following PTX treatment. PTL administration mitigated these changes, bringing biomarker levels closer to normal. Furthermore, antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPX), and glutathione S-transferase (GST) were assessed at gene expression, enzymatic activity, and protein expression levels. The findings indicate that PTL exerts a potent therapeutic effect against PTX-induced cardiotoxicity. These results support the cardioprotective potential of PTL, suggesting that it mitigates PTX-induced oxidative stress and inflammatory responses.