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

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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.

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(A) Cardio protective effect of MO against DOX-induced cardiac damage, (A) serum cardiac injury markers: AST, CK and CK-MB activities in serum. Data are represented mean ± S.E.M. of seven independent rats of each group. a P<0.05 vs. control; b P<0.05 vs. DOX. (B) Histopathological changes. (B) Histopathological changes. Light micrographs of heart sections from control rats showing normal heart architecture, heart sections from DOX groups (DOX1-DOX4) showing focal necrosis with eosinophilic cytoplasm and pyknotic nuclei (arrows) and degeneration of myocardial fibers (d), hemorrhage (h) with inflammatory cell infiltration () and edema (e), In the DOX + LD of MO group, less focal necrosis of muscle fiber and inflammatory cell infiltration (*) with mild edema (e) were noted on cardiac tissue sections. DOX and MD of MO groups showed less degree of degeneration (d), edema (e) and inflammation (*). Animals treated with DOX and HD of MO showed better-preserved appearance of myocardial fibers with mild degree of (e). X 200.
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pone.0167049.g001: (A) Cardio protective effect of MO against DOX-induced cardiac damage, (A) serum cardiac injury markers: AST, CK and CK-MB activities in serum. Data are represented mean ± S.E.M. of seven independent rats of each group. a P<0.05 vs. control; b P<0.05 vs. DOX. (B) Histopathological changes. (B) Histopathological changes. Light micrographs of heart sections from control rats showing normal heart architecture, heart sections from DOX groups (DOX1-DOX4) showing focal necrosis with eosinophilic cytoplasm and pyknotic nuclei (arrows) and degeneration of myocardial fibers (d), hemorrhage (h) with inflammatory cell infiltration () and edema (e), In the DOX + LD of MO group, less focal necrosis of muscle fiber and inflammatory cell infiltration (*) with mild edema (e) were noted on cardiac tissue sections. DOX and MD of MO groups showed less degree of degeneration (d), edema (e) and inflammation (*). Animals treated with DOX and HD of MO showed better-preserved appearance of myocardial fibers with mild degree of (e). X 200.

Mentions: Activities of serum markers, AST and CK, indicating myocardial injury, were significantly elevated in DOX-intoxicated group compared with control. The pretreatment with different doses of MO significantly attenuated the increase in AST, CK and CK-MB levels in DOX-treated group. The decrease in AST, CK and CK-MB activities were dose-dependent while the best protective effect was observed at a high dose of MO (Fig 1A).


Melissa officinalis Protects against Doxorubicin-Induced Cardiotoxicity in Rats and Potentiates Its Anticancer Activity on MCF-7 Cells
(A) Cardio protective effect of MO against DOX-induced cardiac damage, (A) serum cardiac injury markers: AST, CK and CK-MB activities in serum. Data are represented mean ± S.E.M. of seven independent rats of each group. a P<0.05 vs. control; b P<0.05 vs. DOX. (B) Histopathological changes. (B) Histopathological changes. Light micrographs of heart sections from control rats showing normal heart architecture, heart sections from DOX groups (DOX1-DOX4) showing focal necrosis with eosinophilic cytoplasm and pyknotic nuclei (arrows) and degeneration of myocardial fibers (d), hemorrhage (h) with inflammatory cell infiltration () and edema (e), In the DOX + LD of MO group, less focal necrosis of muscle fiber and inflammatory cell infiltration (*) with mild edema (e) were noted on cardiac tissue sections. DOX and MD of MO groups showed less degree of degeneration (d), edema (e) and inflammation (*). Animals treated with DOX and HD of MO showed better-preserved appearance of myocardial fibers with mild degree of (e). X 200.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120835&req=5

pone.0167049.g001: (A) Cardio protective effect of MO against DOX-induced cardiac damage, (A) serum cardiac injury markers: AST, CK and CK-MB activities in serum. Data are represented mean ± S.E.M. of seven independent rats of each group. a P<0.05 vs. control; b P<0.05 vs. DOX. (B) Histopathological changes. (B) Histopathological changes. Light micrographs of heart sections from control rats showing normal heart architecture, heart sections from DOX groups (DOX1-DOX4) showing focal necrosis with eosinophilic cytoplasm and pyknotic nuclei (arrows) and degeneration of myocardial fibers (d), hemorrhage (h) with inflammatory cell infiltration () and edema (e), In the DOX + LD of MO group, less focal necrosis of muscle fiber and inflammatory cell infiltration (*) with mild edema (e) were noted on cardiac tissue sections. DOX and MD of MO groups showed less degree of degeneration (d), edema (e) and inflammation (*). Animals treated with DOX and HD of MO showed better-preserved appearance of myocardial fibers with mild degree of (e). X 200.
Mentions: Activities of serum markers, AST and CK, indicating myocardial injury, were significantly elevated in DOX-intoxicated group compared with control. The pretreatment with different doses of MO significantly attenuated the increase in AST, CK and CK-MB levels in DOX-treated group. The decrease in AST, CK and CK-MB activities were dose-dependent while the best protective effect was observed at a high dose of MO (Fig 1A).

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus