Anti-fibrotic effect of meloxicam in a murine lung fibrosis model.
A murine lung fibrosis model has been induced by challenging male Swiss albino mice with a fibrotic dose of bleomycin (10 mg/kg body weight, s.c.) twice weekly for 6 weeks. The model has been characterized and confirmed biochemically, histologically and morphometrically. Keeping in mind that inflammation is the forerunner of lung fibrosis, we have investigated the possible anti-fibrotic effect of meloxicam; a selective COX-2 inhibitor, in this lung fibrosis paradigm. When administered ahead of bleomycin challenge, meloxicam significantly reduced the lung content of hydroxyproline; the backbone of collagen matrix. This was further confirmed by the lower collagen deposition as revealed by histochemical examination of lung sections. Meloxicam had also anti-oxidant effect as shown by increase in lung reduced glutathione (GSH) level and decreases in lung malonedialdehyde (MDA) content and myeloperoxidase (MPO) activity. Besides, meloxicam has shown an apparent angiostatic activity. Histologically, meloxicam lessened lung inflammation and fibrotic changes induced by bleomycin. Taken together, one could conclude that meloxicam has shown anti-fibrotic effect in the bleomycin lung fibrosis model. Apart from its well-known anti-inflammatory potential, this anti-fibrotic action of meloxicam resides most probably, at least partly, in its anti-oxidant and angiostatic effects.
Arafa
Hossam M M
HM
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. hmmarafa@yahoo.com
Abdel-Wahab
Mohamed H
MH
El-Shafeey
Mohamed F
MF
Badary
Osama A
OA
Hamada
Farid M A
FM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001761:Bleomycin; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006909:Hydroxyproline / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D000077239:Meloxicam; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D001761:Bleomycin; D008315:Malondialdehyde; D003094:Collagen; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D006909:Hydroxyproline; D000077239:Meloxicam