Parthenolide mitigates paclitaxel-induced cardiotoxicity in rats by reducing oxidative stress and inflammation

Chemotherapeutic agents like paclitaxel (PTX) are highly effective against various cancers but often induce severe side effects, including cardiotoxicity, which can limit their clinical utility and impact patient quality of life. This cardiotoxicity is frequently linked to increased oxidative stress, inflammation, and DNA damage within cardiac tissues. Current strategies to mitigate these effects are often insufficient, highlighting an urgent need for novel cardioprotective agents. Parthenolide, a natural compound from Tanacetum parthenium, is recognized for its anti-inflammatory and antioxidant properties, making it a promising candidate to address this therapeutic gap.

This preclinical study utilized 48 male Sprague-Dawley rats, divided into 6 groups, to investigate parthenolide's effects. The control group received no intervention. The second group received 8 mg/kg PTX. A vehicle control group received dimethyl sulfoxide (DMSO). The remaining three groups were treated with 1 mg/kg PTL, 2 mg/kg PTL, and 4 mg/kg PTL, respectively, following PTX administration. Researchers assessed oxidative stress biomarkers (glutathione, malondialdehyde), DNA damage (8-hydroxy-2'-deoxyguanosine), and inflammation markers (iNOS, COX-2). Histopathological analyses of cardiac tissue were performed, alongside gene expression, enzymatic activity, and protein expression levels of antioxidant enzymes (SOD, CAT, GR, GPX, GST).

Paclitaxel treatment significantly altered oxidative stress biomarkers, with glutathione levels decreased and malondialdehyde levels increased, indicating substantial oxidative damage. However, Parthenolide administration at 1, 2, and 4 mg/kg effectively restored these levels to physiological ranges. Histopathological examinations revealed that PTX caused severe pathological alterations in cardiac tissue, including hemorrhage and mononuclear cell infiltration. > Parthenolide treatment substantially ameliorated these histopathological lesions, demonstrating significant cardioprotection. Furthermore, 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, a key indicator of DNA damage, were significantly elevated following PTX treatment. Inflammatory markers, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), also showed significant increases. Parthenolide administration consistently mitigated these PTX-induced changes, bringing biomarker levels closer to normal. The study also found that antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPX), and glutathione S-transferase (GST), were modulated by Parthenolide across gene expression, enzymatic activity, and protein expression levels, supporting its antioxidant mechanism.