Gad M Z, Khattab M
Biochemistry Department, Faculty of Pharmacy, Cairo University, Egypt.
Arzneimittelforschung. 2000 May;50(5):449-55. doi: 10.1055/s-0031-1300229.
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.
在两种炎症模型中，即角叉菜胶肉芽肿气袋（急性模型）和弗氏佐剂诱导的大鼠关节炎（慢性模型），研究了由组成型（cNOS）和诱导型（iNOS）一氧化氮合酶产生的一氧化氮（NO）的作用及其与氧衍生自由基和前列腺素的关系。通过测量NO和前列腺素E2（PGE2）水平以及在注射角叉菜胶4小时后酶N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）向肉芽肿袋渗出液中的溶酶体泄漏来评估炎症。在佐剂注射4天（早期）或16天（晚期）后，通过评估爪体积以及测定血清NO、脂质过氧化物（LP）和PGE2水平来评估佐剂诱导的关节炎。研究结果表明，在注射角叉菜胶之前或佐剂性关节炎发展过程中，给予NG - 硝基 - L - 精氨酸甲酯（L - NAME，非选择性cNOS/iNOS抑制剂）或氨基胍（AG，选择性iNOS抑制剂），可使肉芽肿炎性渗出液中的NO和PGE2水平以及NAG活性显著降低，而在佐剂模型中，与未治疗的大鼠相比，爪体积和血清NO水平有所降低。用L - 精氨酸进行类似处理未能使所测参数产生显著变化。其他观察结果包括：佐剂性关节炎早期和晚期结果之间无明显差异；佐剂性关节炎炎症中NO、LP和PGE2水平之间无明确相关性，且NOS抑制剂无法改变佐剂诱导性关节炎期间升高的血清LP水平。这些数据进一步证明NO参与了急性和慢性炎症的发展，并且NOS抑制剂具有潜在的抗炎活性。需要进一步研究来阐明NO与其他炎症介质相互作用的机制。
