Al-Majed A A, Khattab M, Raza M, Al-Shabanah O A, Mostafa A M
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
Inflamm Res. 2003 Sep;52(9):378-82. doi: 10.1007/s00011-003-1189-1.
To investigate whether aminoguanidine (AG) treatment enhances the anti-inflammatory effect of diclofenac in an acute inflammation model in rats.
In 48 rats carrageenan-induced paw edema was used as an acute inflammation model. Inflammatory activity was assessed at 1.5, 3 and 6 h after sub-planter injection of carrageenan (0.1 ml of a 1% solution in 0.85% saline). The anti-inflammatory effect of diclofenac (25 mg/kg, i.p.) was studied in comparison to that of the selective inducible nitric oxide synthase (iNOS) inhibitor, AG, and of nitric oxide donor, sodium nitroprusside (SNP).
AG, failed to inhibit inflammation during the first 3 h following carrageenan administration, but caused a slight, although statistically insignificant inhibition at 6 h. Diclofenac significantly reduced the carrageenan-induced edema in rat paw at all the time points studied. Administration of diclofenac after AG pretreatment caused significant (P < 0.001) reduction in edema that was double that of diclofenac alone 6 h after carrageenan injection. Administration of SNP as a single dose after AG pretreatment prevented any potentiation of anti-inflammatory response that was observed in the case of AG combined with diclofenac treatment.
These results show that AG markedly potentiates the anti-inflammatory activity of diclofenac at 6 h and this potentiation effect is nitric oxide-dependent.
在大鼠急性炎症模型中研究氨基胍（AG）治疗是否能增强双氯芬酸的抗炎作用。
以角叉菜胶诱导的大鼠足爪水肿作为急性炎症模型，共48只大鼠。在足底注射角叉菜胶（0.1 ml含1%角叉菜胶的0.85%盐水溶液）后1.5、3和6小时评估炎症活性。将双氯芬酸（25 mg/kg，腹腔注射）的抗炎作用与选择性诱导型一氧化氮合酶（iNOS）抑制剂AG以及一氧化氮供体硝普钠（SNP）的抗炎作用进行比较研究。
AG在角叉菜胶给药后的前3小时未能抑制炎症，但在6小时时引起了轻微的抑制作用，尽管在统计学上无显著意义。双氯芬酸在所有研究时间点均显著减轻了角叉菜胶诱导的大鼠足爪水肿。AG预处理后给予双氯芬酸导致水肿显著（P < 0.001）减轻，在角叉菜胶注射6小时后，减轻程度是单独使用双氯芬酸的两倍。AG预处理后单剂量给予SNP可阻止在AG与双氯芬酸联合治疗中观察到的抗炎反应增强。
这些结果表明，AG在6小时时显著增强了双氯芬酸的抗炎活性，且这种增强作用依赖于一氧化氮。
