Khattab Mahmoud M
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Eur J Pharmacol. 2006 Oct 24;548(1-3):167-73. doi: 10.1016/j.ejphar.2006.08.007. Epub 2006 Aug 15.
Carrageenan produces both inflammation and pain when injected in rat paws via enhancement of the formation of reactive oxygen species. We have tested the effect of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), a membrane-permeable superoxide dismutase (SOD) mimetic in carrageenan-induced rat paw edema. Treatment of rats with TEMPOL (15, 30, and 60 mg/kg, 15 min prior to carrageenan) inhibited the paw edema. Furthermore, treatment of rats with the SOD inhibitor diethylthiocarbamate (DETCA, 100 mg/kg, 1 h before carrageenan) enhanced the carrageenan-induced paw edema. Co-administration of peroxynitrite with carrageenan produced a similar fortification of the carrageenan-induced edema. Prior treatment of rats with TEMPOL (30 mg/kg) inhibited the enhancement produced by DETCA treatment (endogenous superoxide anion stress) as well as that produced by the peroxynitrite stress. The effect of TEMPOL as well as the influence of superoxide anion and peroxynitrite stresses was also tested in carrageenan-induced hyperalgesia model. Carrageenan (500 mug/paw) produced significant hyperalgesia presented as shortening of withdrawal latency times using hot plate (52 degrees C) starting 30 min after carrageenan and lasting for 3 h. TEMPOL (60 mg/kg, injected 15 min before carrageenan) ameliorated this hyperalgesia during the first 2 h. Concurrent administration of peroxynitrite promptly intensified the carrageenan hyperalgesia. TEMPOL (60 mg/kg, 15 min before peroxynitrite-carrageenan) inhibited the peroxynitrite enhancement of carrageenan hyperalgesia when tested at 60 min after injection of the cocktail. The present investigation gives the proof for the effectiveness of TEMPOL as anti-inflammation and analgesic agents in carrageenan-induced model of inflammation and hyperalgesia. It further indicated the importance of superoxide anion and peroxynitrite in acute inflammation and inflammatory pain. This raises the chances for considering pharmacologic interventions that interrupt superoxide anion and peroxynitrite stress for putative alternative agents as anti-inflammatory analgesic new medical strategies.
角叉菜胶通过增强活性氧的形成，在注射到大鼠爪子时会引发炎症和疼痛。我们测试了4-羟基-2,2,6,6-四甲基哌啶-N-氧基（TEMPOL）的作用，它是一种可透过细胞膜的超氧化物歧化酶（SOD）模拟物，用于角叉菜胶诱导的大鼠爪水肿实验。用TEMPOL（15、30和60mg/kg，在注射角叉菜胶前15分钟）处理大鼠，可抑制爪水肿。此外，用超氧化物歧化酶抑制剂二乙基硫代氨基甲酸盐（DETCA，100mg/kg，在注射角叉菜胶前1小时）处理大鼠，会增强角叉菜胶诱导的爪水肿。将过氧亚硝酸盐与角叉菜胶共同注射，会产生类似的对角叉菜胶诱导水肿的增强作用。用TEMPOL（30mg/kg）预先处理大鼠，可抑制DETCA处理（内源性超氧阴离子应激）以及过氧亚硝酸盐应激所产生的水肿增强作用。还在角叉菜胶诱导的痛觉过敏模型中测试了TEMPOL的作用以及超氧阴离子和过氧亚硝酸盐应激的影响。角叉菜胶（500μg/爪）会产生显著的痛觉过敏，表现为在注射角叉菜胶30分钟后，使用热板（52℃）时缩爪潜伏期缩短，并持续3小时。TEMPOL（60mg/kg，在注射角叉菜胶前15分钟注射）在前2小时内减轻了这种痛觉过敏。同时注射过氧亚硝酸盐会立即加剧角叉菜胶诱导的痛觉过敏。当在注射混合剂60分钟后进行测试时，TEMPOL（60mg/kg，在注射过氧亚硝酸盐-角叉菜胶前15分钟）抑制了过氧亚硝酸盐对角叉菜胶痛觉过敏的增强作用。本研究证明了TEMPOL在角叉菜胶诱导的炎症和痛觉过敏模型中作为抗炎和镇痛剂的有效性。它进一步表明了超氧阴离子和过氧亚硝酸盐在急性炎症和炎性疼痛中的重要性。这增加了考虑采用药物干预来阻断超氧阴离子和过氧亚硝酸盐应激，作为潜在的抗炎镇痛新医学策略的替代药物的可能性。
