Abstract
Cardiotoxicity is a limiting factor of doxorubicin (DOX)-based anticancer therapy. Due to its beneficial effects, we investigated whether standardized extract of Melissa officinalis (MO) can attenuate doxorubicin-induced cardiotoxicity and can potentiate the efficacy of DOX against human breast cancer cells. MO was administered orally to male albino rats once daily for 10 consecutive days at doses of 250, 500 and 750 mg/kg b.wt. DOX (15 mg/kg b.wt. i.p.) was administered on the 8th day. MO protected against DOX-induced leakage of cardiac enzymes and histopathological changes. MO ameliorated DOX-induced oxidative stress as evidenced by decreasing lipid peroxidation, protein oxidation and total oxidant capacity depletion and by increasing antioxidant capacity. Additionally, MO pretreatment inhibited inflammatory responses to DOX by decreasing the expressions of nuclear factor kappa-B, tumor necrosis factor-alpha and cyclooxygenase-2 and the activity of myeloperoxidase. MO ameliorated DOX-induced apoptotic tissue damage in heart of rats. In vitro study showed that MO augmented the anticancer efficacy of DOX in human breast cancer cells (MCF-7) and potentiated oxidative damage and apoptosis. Thus, combination of DOX and MO may prove future cancer treatment protocols safer and more efficient.
Highlights
Doxorubicin (DOX), an anthracycline antibiotic, is regularly used to treat various malignancies, including solid tumors, lymphoma and leukemia
Melissa officinalis Protects against Cardiotoxicity & Possesses Anti Breast Cancer Activity aminotransferase; MDA, malondialdehyde; CAT, catalase; CK, Creatine kinase; CK-MB, CK isoenzyme-MB; COX-2, Cyclooxygenase-2; DOX, Doxorubicin; DPPH, 1,1-diphenyl-2-picrylhydrazyl; MPO, Myeloperoxidase; NF-kB, nuclear factorkappa B; nitrite oxide (NO), nitric oxide; P.carbonyl, protein carbonyl; Superoxide dismutase (SOD), superoxide dismutase; TNF-α, Tumor necrosis alpha
The pretreatment with different doses of Melissa officinalis (MO) significantly attenuated the increase in AST, CK and CK-MB levels in DOX-treated group
Summary
Doxorubicin (DOX), an anthracycline antibiotic, is regularly used to treat various malignancies, including solid tumors, lymphoma and leukemia. Melissa officinalis Protects against Cardiotoxicity & Possesses Anti Breast Cancer Activity aminotransferase; MDA, malondialdehyde; CAT, catalase; CK, Creatine kinase; CK-MB, CK isoenzyme-MB; COX-2, Cyclooxygenase-2; DOX, Doxorubicin; DPPH, 1,1-diphenyl-2-picrylhydrazyl; MPO, Myeloperoxidase; NF-kB, nuclear factorkappa B; NO, nitric oxide; P.carbonyl, protein carbonyl; SOD, superoxide dismutase; TNF-α, Tumor necrosis alpha. Success [3,4] While some of those agents such as vitamin E failed to inhibit DOX cardiotoxicity [5] others, such as deferasirox (an iron chelator) increased its toxicity [6]. Cardiotoxicity associated with DOX treatment has been successfully prevented by different medicinal plants [7,8,9]. It is well justified to explore more plant derived-natural compounds that prevent the cardiotoxicity of DOX and enhance its chemotherapeutic efficacy
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