title: Modulatory effects of meloxicam on cardiotoxicity and antitumor activity of doxorubicin in mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, P.O. Box 30001, El-Madinah, El-Munaworah, Saudi Arabia, memymahmoud@yahoo.com.
authors: Memy H
authors: MH
authors: Hassan
authors: Hesham A
authors: HA
authors: El-Beshbishy
authors: Hamdy
authors: H
authors: Aly
authors: Sabry M
authors: SM
authors: Attia
authors: Saleh A
authors: SA
authors: Bahashwan
authors: Mohamed M
authors: MM
authors: Ghobara
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077239:Meloxicam; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D052246:Cyclooxygenase 2 Inhibitors; D013843:Thiazines; D013844:Thiazoles; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione; D015232:Dinoprostone; D000077239:Meloxicam