Antinflammatory Activity Of A New Pyrazolon Drug

O.A. Georgewill; U.O. Georgewill; R.N.P. Nwankwoala

摘要

Using carrageenan-induced paw inflammation model in rats, the anti-inflammatory effects of 4-acetyl – 1 phenyl 1-3 methyl 1 pyrazolone (HAP) were investigated and compared with those of standard anti-inflammatory agents viz indomethacin, HTFP (4-triflouroacetyl-1 phenyl-3 methyl pyrazolone) and hydrocortisone. Rats were intraperitoneally administered different doses of HAP, HTFP, indomethacin and hydrocortisone and one hour thereafter, inflammation was induced by injecting carrageenan into the left foot. The right foot received saline. Five rats received carrageenan and saline only. Both the left and right feet were measured hourly for inflammatory response for four (4) hours. HAP, HTFP reduced the inflammatory response by 80% whereas hydrocortisone and indomethacin reduced the inflammatory response by 70% and 84% respectively. These results suggest that HAP, a new pyrazolon derivative may possess anti-inflammatory activity comparable to those of standard anti-inflammatory agents. Introduction Phenylbutazone, a pyrazolon drug is useful in the treatment of acute gout, rheumatoid arthritis and allied disorders (Flower 1974; Fowler 1983; Flower 1983; Hart and Huskisson, 1984) because it possesses anti-inflammatory property (Yu, 1974; Hart and Huskisson, 1984. The therapeutic usefulness of phenylbutazone is limited because it possesses toxic side effects which include peptic ulcer (or its reactivation) with hemorrhage or perforation, hypersensitivity reactions of the serum sickness type, ulcerative stomatitis, hepatitis, nephritis, aplastic anemia, leucopenia, agranulocytosis and thrombocytopenia (Yu, 1974; Flower, 1983). Attempts have therefore been made to modify the structure of phenylbutazone in order to produce drugs with potent anti-inflammatory property but less toxic effects. 4-acetyl-1-phenyl-3methyl pyrazolone (HAP) is one such drug synthesized in our chemistry laboratory.This drug was therefore subjected to pharmacological test in order to determine whether it possesses anti-inflammatory effects and hence this investigation. Materials and methods AnimalsAdult (5-10 weeks old) albino Wister rats of both sexes weighing 100g-150g were used. The animals were obtained from the animal house of University of Port Harcourt and kept in the Departmental animal house at least 7 days before use. They were fed on chicken mash supplied by Superfeeds Nigeria Ltd. and were given drinking water ad libitum.Drugs and Reagents Indomethacin, hydrocortisone and carrageenan were obtained from sigma chemical U.K. HAP and HTFP were supplied from the department of Chemistry, University of Port Harcourt.Induction of inflammationInflammation was induced by injecting 0.1ml of 1% carrageenan solution into the foot of the rat (Thompson and Fowler, 1981).ExperimentsThe experiment was divided into two groups viz the control group and the drug treated group. The control group consisted of five (5) rats and these received intraperitoneal administration of 0.1ml of 1% carrageenan into the left foot whereas the right foot was given 0.1ml saline. The paw size was subsequently measured hourly for four (4) hours.In the drug treated group, 10mg/kg HAP, 10mg/kg HTFP, 10mg/kg indomethacin and 10mg.kg hydrocortisone were administered intraperitoneally one were administered intraperitoneally one hour before the induction of inflammation in the rats. Each drug was given to five (5) rats. The paw wize was then measured hourly for four (4) hours. Students t-test was used to test for statistical significance. A P value equal to or less than 0.05 was considered statistically significant. Where indicated, the anti-inflammatory responses were presented as means ± standard error (SE). The frequency distribution graphs were constructed from the results of anti-inflammatory response studies recorded at 4 hours after drug injection. Results HAP, HTFP, indomethacin and hydrocortisone significantly (p < 0.05) reduced the carrageenan induced inflammation in rats. A dose of 10/k

机译：使用角叉菜胶诱导的大鼠足爪炎症模型，研究了4-乙酰基-1苯基1-3甲基1吡唑啉酮（HAP）的抗炎作用，并将其与标准消炎药，即消炎痛HTFP（4-三氟乙酰基-1苯基-3甲基吡唑啉酮）和氢化可的松。给大鼠腹膜内施用不同剂量的HAP，HTFP，消炎痛和氢化可的松，一小时后，通过向左脚注射角叉菜胶诱导炎症。右脚接受生理盐水。五只大鼠仅接受角叉菜胶和生理盐水。每小时测量左脚和右脚的炎症反应四（4）小时。 HAP，HTFP使炎性反应降低80％，而氢化可的松和消炎痛分别使炎性反应降低70％和84％。这些结果表明，新的吡唑啉酮衍生物HAP可能具有与标准消炎药相当的消炎活性。简介吡唑酮是一种吡唑啉酮药物，可用于治疗急性痛风，类风湿性关节炎和相关疾病（Flower 1974; Fowler 1983; Flower 1983; Hart和Huskisson，1984），因为它具有抗炎作用（Yu，1974; Hart and Huskisson，1984年。苯基丁氮酮的治疗用途有限，因为它具有毒性副作用，包括消化性溃疡（或其活化）伴有出血或穿孔，血清病类型的超敏反应，溃疡性口腔炎，肝炎，肾炎，再生障碍性贫血，白细胞减少症，粒细胞缺乏症和血小板减少症（Yu，1974; Flower，1983）。因此，人们尝试改变苯基丁a的结构，以生产具有有效的抗炎特性但毒性较小的药物4-乙酰基-1-苯基-3甲基吡唑啉酮（HAP）是我们化学实验室合成的一种药物，因此对该药物进行了药理测试以确定其它具有抗炎作用，因此值得研究。材料和方法动物使用成年（5-10周龄）成年体重为100g-150g的两性白化病Wister大鼠。这些动物获自哈科特港大学的动物舍，并在使用前至少7天保存在部门动物舍中。他们以Superfeeds Nigeria Ltd.提供的鸡肉为食，并随意喝水。药物和试剂吲哚美辛，氢化可的松和角叉菜胶是从sigma chemical UK HAP获得的，而HTFP是从哈科特港大学的化学系获得的。炎症的诱导通过向大鼠足部注射0.1ml的1％角叉菜胶溶液来诱导炎症（Thompson和Fowler，1981）。实验将实验分为两组，即对照组和药物治疗组。对照组由五（5）只大鼠组成，这些大鼠腹膜内给予左脚0.1ml 1％角叉菜胶，而右脚则给予0.1ml生理盐水。随后每小时测量爪子大小四（4）小时。在药物治疗组中，在腹腔注射前1小时腹膜内施用10mg / kg HAP，10mg / kg HTFP，10mg / kg消炎痛和10mg.kg氢化可的松。诱导大鼠发炎。将每种药物给予五（5）只大鼠。然后每小时测量爪子四（4）小时。学生t检验用于检验统计学显着性。 P值等于或小于0.05被认为具有统计学意义。在指出的地方，抗炎反应表示为平均值±标准误差（SE）。频率分布图由药物注射后4小时记录的抗炎反应研究结果构建而成。结果HAP，HTFP，消炎痛和氢化可的松显着（p <0.05）减轻了角叉菜胶诱发的大鼠炎症。剂量为10 / k

Antinflammatory Activity Of A New Pyrazolon Drug

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