[Changes in nitric oxide, prostaglandins and myeloperoxidase activity in acrolein-induced cystitis in rats].
To investigate the role of substance P (sP), nitric oxide (ON) and prostaglandins (PGs) in acrolein (ACR)-induced cystitis, we studied the changes induced by ACR on bladder inducible nitric oxide synthase (iNOS) and mieloperoxidase (MPO) activities, along with PGs and NO metabolites levels. Sprague-Dawley male rats received i.p. ACR (5 mg/Kg) plus one of the following treatments: Group 1: saline 0.10 mL/100g i.p.; Group 2: Win-51.708 (WIN) 25 mg/Kg i.p.; Group 3: S-metilisothiourea (MITU) 35 mg/Kg i.p.; Group 4: Rofecoxib(ROF) 20 mg/Kg o.p.; Group 5: Meloxicam(MEL) 25 mg/Kg i.p.; Group 6: combination MITU+MEL. ACR-induced mortality was partially prevented by WIN (NK1 antagonist) and MITU (iNOS inhibitor). Animals that survived after 24h of ACR exposure, had histological inflammatory changes in bladder along with increased MPO activity. There was augmentation of nitrates+nitrites and of PGs. WIN didn't prevent any of these effects. ROF and MEL (COX-2 inhibitors) partially protected against bladder inflammation; MITU pre-treatment was able to prevent these changes and those of NO metabolites levels. The MITU+MEL combination produced the highest protection against ACR-induced damage. These results suggest that NO produced via iNOS and PGs produced by COX-1/COX-2, have an important role in the pathogenesis of cystitis induced by ACR. ACR could stimulate iNOS and COX-1/COX-2, producing lymphocyte migration and increases of NO and PGs.
Cátedra de Fisiología, Escuela de Medicina "Dr. Luis Razetti", Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.
Beatriz
B
Linares-Fernández
Anna B
AB
Alfieri
D000171:Acrolein / Q000633:toxicity; D000731:Androstanes / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D015232:Dinoprostone / Q000652:urine; D004353:Drug Evaluation, Preclinical; D007783:Lactones / Q000627:therapeutic use; D008297:Male; D000077239:Meloxicam; D008565:Membrane Proteins / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D009569:Nitric Oxide / Q000032:analysis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000032:analysis*; D011453:Prostaglandins / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000627:therapeutic use; D013843:Thiazines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D001743:Urinary Bladder / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology
D000731:Androstanes; D001562:Benzimidazoles; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D008565:Membrane Proteins; D064729:Neurokinin-1 Receptor Antagonists; D011453:Prostaglandins; D013450:Sulfones; D013843:Thiazines; D013844:Thiazoles; C086111:WIN 51708; C116926:rofecoxib; D009569:Nitric Oxide; D000171:Acrolein; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; D000077239:Meloxicam