Melissa officinalis Protects against Doxorubicin-Induced Cardiotoxicity in Rats and Potentiates Its Anticancer Activity on MCF-7 Cells

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.

Cardioprotective Potential of Murraya koenigii (L.) Spreng. Leaf Extract against Doxorubicin‐Induced Cardiotoxicity in Rats

“…Pretreatment with aqueous leaf extract showed increased level of total antioxidant status confirming the antioxidant activity of Murraya leaf extract. Results of this present study were in harmony with previous studies done by Al-Harthi et al and Hamza et al [51,55]. e superoxide anions and their derivatives specially the highly reactive and damaging hydroxyl radicals formed in doxorubicin metabolism cause the lipid peroxidation of the cell membrane [51].…”

“…leaf extract significantly reduced the lipid peroxidation suggesting the antioxidant potential of the plant. Many previous studies on natural products or other compounds with high amount of antioxidants have shown a reduction of lipid peroxidation in doxorubicin-induced cardiotoxicity [27,51,52,54,55].…”

“…Activation of nucleotide-binding oligomerization domain-(NOD-) like receptor protein 3 (NLRP3) increases release of proinflammtory cytokines in the myocardium such as tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). ese proinflammatory cytokines concurrently may increase the MPO activity [55]. erefore, measurement of MPO activity in serum is considered as a reliable marker to identify inflammation in doxorubicininduced cardiotoxicity.…”

Ursolic acid prevents doxorubicin‐induced cardiac toxicity in mice through eNOS activation and inhibition of eNOS uncoupling

“…The mechanisms of doxorubicin‐associated cardiac toxicity are not fully elucidated; however, cardiac cell apoptosis by ROS is a known side effect of doxorubicin. Multiple reports have demonstrated that doxorubicin‐induced cardiac toxicity is decreased by anti‐apoptotic methods in various animal models . It is known that ursolic acid protects the heart from ischaemic reperfusion injury or infarction by anti‐apoptotic activities .…”

Ameliorative effect of rosiglitazone, a peroxisome proliferator gamma agonist on adriamycin‐induced cardio toxicity via suppressing oxidative stress and apoptosis

“…The supernatant sample was used for estimating antioxidant enzymes markers. The total protein content was measured by the technique designed by Taylor et al The catalase (CAT) action was evaluated by Liu et al method . The superoxide dismutase (SOD) action was assessed by Mayer et al method .…”