Batu O S, Erol K
Department of Pharmacology, School of Medicine, Akdeniz University, Antalya, Turkey.
Inflammopharmacology. 2007 Dec;15(6):260-5. doi: 10.1007/s10787-007-1605-1.
Celecoxib is a frequently used nonsteroidal anti-inflammatory drug (NSAID) in the treatment of rheumatoid arthritis and osteoarthritis. It selectively inhibits cyclooxygenase II (COX-2) enzyme which is responsible for the production of proinflammatory prostanoids. It has been proposed that since it does not significantly inhibit COX-1, an isoenzyme responsible for the production of cytoprotective prostanoids, celecoxib has fewer side effects in the stomach. Dipyrone which is a drug with potent analgesic activity has no significant inhibitory effect on COX. In this study, the effects of celecoxib and dipyrone on experimentally induced gastric ulcers in rats were compared with respect to different parameters. In the first experiment, in an attempt to identify the best dose for both drugs, a histamine-induced gastric ulcer model was used and each drug was administered at 5, 25 and 100 mg/kg doses, and ulcer index, acidity and mucus secretion were measured in the stomach. The best dose was determined to be 5 mg/kg for both drugs. Celecoxib was found to delay ulcer healing when compared to dipyrone especially when ulcer index was used as measure. In the second experiment, ulcer index, acidity, mucus secretion, and the levels of myeloperoxidase (MPO), lipid peroxide (MDA), non-protein sulfhydryl groups (NP-SH), and prostaglandin E2 (PGE2) were investigated in the stomach of rats with gastric ulcers induced by histamine, stress and diethyldithiocarbamate (DDC). While celecoxib increased the ulcer index in stress-induced ulcer, dipyrone decreased the index in DDC-induced ulcer. Celecoxib also caused a significant increase of gastric mucus secretion in histamine-induced ulcer model. Gastric lipid peroxidation was significantly increased by dipyrone in the control group without gastric ulcer induction, whereas it was significantly increased by celecoxib in the histamine-induced and stress-induced ulcer groups. Dipyrone promoted a decrease in gastric NP-SH levels in the control group with stress-induced ulcer. With respect to gastric MPO activity, dipyrone caused a decrease in the histamine-induced ulcer group but it caused an increase in the stress-induced and DDC-induced ulcer groups. Gastric PGE2 levels in the control group without gastric ulcer induction were not affected by celecoxib while they were increased by dipyrone. In conclusion, celecoxib prompted the formation of experimentally induced gastric ulcers more than did dipyrone. The study was supported by Osmangazi University Research Funds.
塞来昔布是一种常用于治疗类风湿性关节炎和骨关节炎的非甾体抗炎药（NSAID）。它选择性抑制环氧化酶II（COX-2），该酶负责促炎性前列腺素的产生。有人提出，由于它不会显著抑制COX-1（一种负责产生细胞保护性前列腺素的同工酶），塞来昔布在胃部的副作用较少。安乃近是一种具有强效镇痛活性的药物，对COX没有显著抑制作用。在本研究中，比较了塞来昔布和安乃近在不同参数方面对大鼠实验性胃溃疡的影响。在第一个实验中，为了确定两种药物的最佳剂量，使用了组胺诱导的胃溃疡模型，每种药物分别以5、25和100mg/kg的剂量给药，并测量胃中的溃疡指数、酸度和黏液分泌。确定两种药物的最佳剂量均为5mg/kg。与安乃近相比，尤其是以溃疡指数作为衡量指标时，发现塞来昔布会延迟溃疡愈合。在第二个实验中，研究了组胺、应激和二乙基二硫代氨基甲酸盐（DDC）诱导的胃溃疡大鼠胃中的溃疡指数、酸度、黏液分泌以及髓过氧化物酶（MPO）、脂质过氧化物（MDA）、非蛋白巯基（NP-SH）和前列腺素E2（PGE2）水平。虽然塞来昔布在应激诱导的溃疡中增加了溃疡指数，但安乃近在DDC诱导的溃疡中降低了该指数。在组胺诱导的溃疡模型中，塞来昔布还导致胃黏液分泌显著增加。在未诱导胃溃疡的对照组中，安乃近显著增加了胃脂质过氧化，而在组胺诱导和应激诱导的溃疡组中，塞来昔布显著增加了胃脂质过氧化。在应激诱导溃疡的对照组中，安乃近促使胃NP-SH水平降低。关于胃MPO活性，安乃近在组胺诱导的溃疡组中导致降低，但在应激诱导和DDC诱导的溃疡组中导致升高。在未诱导胃溃疡的对照组中，塞来昔布对胃PGE2水平没有影响，而安乃近使其升高。总之，与安乃近相比，塞来昔布更易促使实验性胃溃疡的形成。本研究得到奥斯曼加齐大学研究基金的支持。
