Experimental evaluation of the antinociceptive and anti-inflammatory effects of rosuvastatin and its interaction with celecoxib and paracetamol


Background: Studies revealed that statins can result in a larger mortality benefit than can be readily explained by their cholesterol-lowering effect alone. These benefits might be related to the anti-inflammatory and other effects statins may have.Aim: To find out the extent to which rosuvastatin can be considered as an antinociceptive and anti-inflammatory drug in comparison to two standard drugs; paracetamol and celecoxib. Methods: Mice (a total of 132) of either sex, 3-4 weeks of age, 20-25 gm body weight, were used. Tests for nociception: tail flick, hot plate and formalin tests; and for inflammation (formalin for chronic inflammation, carrageenan-induced paw edema, and TNF alpha level in blood) were used. Rosuvastatin (7mg/kg), paracetamol (40mg/kg), celecoxib (6mg/kg) or their combination were administered orally once daily in a volume of 0.2 ml. TNF alpha level in blood was measured using ELISA kit.Results: The antinociceptive effect of rosuvastatin was mild and was much less than that of paracetamol and celecoxib when tested in the tail-flick, hot-plate and formalin tests. It increased the latency for tail flick by only 13.3% when compared to pre-treatment measurements, and in formalin test, it reduced the licking time by 20.9% in comparison to control. The administration of rosuvastatin with either paracetamol or celecoxib did not add to the antinociceptive effects of the latter two drugs except in formalin test for pain. None of the above mentioned drugs reduced hind-paw edema when measured 24 hours after formalin injection, while they produced a significant edema-reducing effect after 14 days. Again there was no additive effect between rosuvastatin and either paracetamol or celecoxib; in contrast, rosuvastatin reduced nearly all the effects of celecoxib when given in combination. Similar trend was found when edema-induced by carrageenan injection. Conclusion: Rosuvastatin showed a significant antinociceptive effect in tail flick and in formalin test, but not in hot plate test in mice. It had anti-inflammatory and edema-reducing effects in models of inflammation but the effect was less than that of celecoxib and even paracetamol. These rosuvastatin effects did not add to those of paracetamol and had caused a reduction in celecoxib effects, when given in combination, except in formalin test for pain where there were additive effect.