O Georgewill, U Georgewill, R Nwankwoala
anti inflammatory, extract, hydrocortisone, indomethacin, moringa oleifera
O Georgewill, U Georgewill, R Nwankwoala. Antinflammatory Activity Of A New Pyrazolon Drug. The Internet Journal of Pharmacology. 2008 Volume 7 Number 1.
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.
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
Adult (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 inflammation
Inflammation was induced by injecting 0.1ml of 1% carrageenan solution into the foot of the rat (Thompson and Fowler, 1981).
The 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.
HAP, HTFP, indomethacin and hydrocortisone significantly (p < 0.05) reduced the carrageenan induced inflammation in rats. A dose of 10/kg HAP and 10mg/kg HTFR significantly (p < 0.05) reduced the inflammatory response by 80.5 ± 4.0% respectively. At a dose of 10mg/kg hydrocortisone reduced the inflammatory response by 84.5 ± 5.0% whereas 10mg.kg indomethacin reduced the carrageenan induced inflammation by 70.6 ± 3.4%. These results are shown in fig. 2. There was no significant difference in the reduction of the inflammatory response between the HAP treated group, HTFP treated group and the group that received hydrocortisone. However, HAP and HTFP significantly (p < 0.05) reduced inflammatory response when compared with the reduction in inflammatory response observed with indomethacin.
Figure 3. illustrates the sizes of the right and left feet of the rat, four (4) hours after HAP administration. As can be observed, the size of the left foot which was treated with carrageenan has been considerably reduced to a little larger than he size of the right foot which was treated with saline.
Indomethacin and hydrocortisone are effective anti-inflammatory agents (Shen and Winter 1977; Blackwell et al., 1980; Hirata et al., 1980; Rhymer and Genos, 1983). The results of this study confirm this property of indomethacin and hydrocortisone and also demonstrate that the new pyrazolon derivative (HAP) possesses anti-inflammatory property. The anti-inflammatory potency of the new pyrazolon drug (HAP) is comparable to those of the standard anti-inflammatory agents indomethacin and hydrocortisone because 10mg/kg HAP reduced inflammatory response by 80% whereas hydrocortisone and indomethacin at the same does of 10mg/kg reduced the inflammatory response by 84% and 70% respectively.
We had previously reported that HTEP, another new pyrazolon derivative, had anti-inflammatory effects comparable had anti-inflammatory effects comparable to phenylbutazone (Ezeamuzie and Nwankwoala, 1994). In this study the anti-inflammatory property of 10mg/kg HAP was similar in magnitude to that of HTFP because both drugs at equi-concentration reduced carrageenan induced inflammation by about 80%. Because HTEP is structurally different from HAP by the possession of a trifluoro group attached to acetyl group at position 4 of the pyrazolone nucleus (fig. 1) the results of this study suggest that the addition of triflouoro group to acetyl side chain does not enhance the anti-inflammatory potency of the pyrazolon drug.
Having established that HAP possesses anti-inflammatory property, it is now necessary to investigate the degree of toxicity of this new drug. The toxicity studies are currently being carried out in our laboratory