Modulatory effects of meloxicam on cardiotoxicity and antitumor activity of doxorubicin in mice

被引:15
|
作者
Hassan, Memy H. [1 ,2 ]
El-Beshbishy, Hesham A. [3 ,4 ]
Aly, Hamdy [2 ,5 ]
Attia, Sabry M. [2 ,6 ]
Bahashwan, Saleh A. [1 ]
Ghobara, Mohamed M. [3 ,7 ]
机构
[1] Taibah Univ, Coll Pharm, Dept Pharmacol & Toxicol, El Madinah, El Munaworah, Saudi Arabia
[2] Al Azhar Univ, Fac Pharm, Dept Pharmacol & Toxicol, Cairo 11231, Egypt
[3] Taibah Univ, Fac Appl Med Sci, Dept Med Labs Technol, El Madinah, El Munaworah, Saudi Arabia
[4] Al Azhar Univ, Fac Pharm, Dept Biochem, Cairo 11231, Egypt
[5] King Abdel Aziz Univ, Dept Pharmacol & Toxicol, Fac Pharm, Jeddah, Saudi Arabia
[6] King Saud Univ, Fac Pharm, Dept Pharmacol & Toxicol, Riyadh, Saudi Arabia
[7] Tanta Univ, Fac Med, Dept Histol, Tanta, Egypt
关键词
Doxorubicin; Oxidative stress; Quinone reductase; Cyclooxygenase-2; inhibitors; Meloxicam; BREAST-CANCER; DT-DIAPHORASE; NAD(P)H-QUINONE REDUCTASE; CYTOTOXICITY; ADRIAMYCIN; EXPRESSION; EFFICACY; CARCINOGENESIS; GLUTATHIONE; PROTECTION;
D O I
10.1007/s00280-014-2544-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This study was undertaken to assess the possible modulatory effects and mechanisms of meloxicam, a cyclooxygenase-2 inhibitor, on the antitumor activity and cardiotoxicity of doxorubicin in a mice model of mammary carcinoma. Solid tumor mass was developed in female albino mice using Ehrlich carcinoma cells. Forty mice-bearing tumor were divided randomly into four groups for treatment: with saline, meloxicam 10 mg/kg, doxorubicin 5 mg/kg and meloxicam 1 h ahead of doxorubicin, twice weekly for 2 weeks. Tumor volume was followed up and cardiac protective utility was estimated via measuring heart and serum parameters. Meloxicam expressed a non-significant increase in doxorubicin antitumor activity. Conversely, meloxicam significantly (p < 0.01) mitigated doxorubicin-induced elevation of serum cardiac enzymes [creatine kinase, lactate dehydrogenase and troponin-I]; cardiac lipid peroxidations marker; cardiac active caspase-3 content; and cardiac prostaglandin E2 content. Meloxicam significantly abrogated doxorubicin-induced disturbance in heart histology and relative heart weight to body weight. Meloxicam normalized doxorubicin-induced suppression in heart antioxidant enzymes activities and gene expressions [superoxide dismutase, glutathione peroxidase (GSH-Px) and catalase], and heart GSH content. In addition, meloxicam ameliorated doxorubicin-induced disturbance in phase II metabolizing enzyme, cardiac quinone reductase (QR), at activity level and mRNA expression. Meloxicam protects heart against doxorubicin toxicity without affecting its antitumor activity against solid mammary cancer model in mice. This protective effect is attributed to antioxidant effect, antiradical effect, antiinflammatory action, antiapoptotic effect and induction of QR enzyme.
引用
收藏
页码:559 / 569
页数:11
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