title: Modulation of nitric oxide synthesis in inflammation. Relationship to oxygen-derived free radicals and prostaglandin synthesis.
abstract: The role of nitric oxide (NO) derived from constitutive (cNOS) and inducible (iNOS) nitric oxide synthases and its relationship to oxygen-derived free radicals and prostaglandins was investigated in two models of inflammation, namely, carrageenan granuloma air pouch (acute model) and Freund's adjuvant-induced arthritis (chronic model) in rats. Inflammation was assessed by measurement of NO and prostaglandin E2 (PGE2) levels and the lysosomal leakage of the enzyme N-acetyl-B-D-glucosaminidase (NAG) into the exudate of the granuloma pouch 4 h after carrageenan injection. Evaluation of paw volume and determination of serum NO, lipid peroxide (LP), and PGE2 levels were used for the assessment of adjuvant-induced arthritis after either 4 days (early phase) or 16 days (late phase) of adjuvant injection. Results of the study showed that the administration of either NG-nitro-L-arginine methyl ester (L-NAME, non-selective cNOS/iNOS inhibitor) or aminoguanidine (AG, selective iNOS inhibitor), prior to carrageenan injection or during development of adjuvant arthritis, caused a significant reduction in NO and PGE2 levels and in the NAG activity of the granuloma inflammatory exudate, whereas decreases in paw volume and in serum NO level were noticed in the adjuvant model as related to untreated rats. Similar treatment with L-arginine failed to elaborate a significant change in the parameters measured. Other observations included: no noticeable differences between the results of early and late phases of adjuvant arthritis; no clear correlation between NO, LP and PGE2 levels in the adjuvant arthritis inflammation and inability of the NOS inhibitors to modify the levels of serum LP that is increased during adjuvant-induced arthritis. The data give further evidence that NO is implicated in the development of both acute and chronic inflammation and that NOS inhibitors have potential antiinflammatory activity. Further studies are required to unravel the mechanisms by which NO interacts with other mediators of inflammation.
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Cairo University, Egypt. drmzgad@gega.net
authors.forename: M Z
authors.initials: MZ
authors.lastname: Gad
authors.forename: M
authors.initials: M
authors.lastname: Khattab
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002351:Carrageenan; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006099:Granuloma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D005609:Free Radicals; D006146:Guanidines; D011453:Prostaglandins; D009569:Nitric Oxide; D002351:Carrageenan; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D000118:Acetylglucosaminidase; D015232:Dinoprostone; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester