Impact of two selected non-steroidal anti-inflammation drugs flunixin and ketoprofen on peroxynitrite-induced inflammation and serum levels of cortisol and glucose

Introduction: Peroxynitrite, produced naturally in the body from a reaction between nitric oxide and superoxide anion, possess destructive effects against microorganisms. In excess concentrations, however, it may also lead to cellular damage and inflammatory reactions in the host. Non - sterodial anti inflammation drugs (NSAIDs) are used widely in therapy for their anti-inflammatory, analgesic and antipyretic properties. Meanwhile, their adverse effects on endocrine functions should be taken into account. This project aims at the following goals: 1) establishing a new animal model of peroxynitrite-induced inflammation, 2) studying the effect of two selected NSAIDs on these parameters.3) investigating the possible effect of this oxidant on the blood levels of cortisol and glucose. Material & Methods: 24 male guinea pigs were divided into 4 groups (6 animals in each group). Three groups were injected peroxynitrite and the last group, control group, given physiological salt solution in the paw subcutaneously. Following induction of a local inflammatory response, flunixin meglumine and ketoprofen (0.5 mg/0.5 ml) were injected to second and third groups, 5 times with 12h intervals. First and fourth groups were injected saline solution with the same manner. Animals were anesthetized with thiopental (60 mg/kg, i.p.) and a blood sample was collected by heart puncture. The glucose and cortisol levels of blood were determined by routine laboratory techniques. Result: Blood glucose concentration in the animals that only injected peroxynitrite was less than the control group. In addition, groups which were given drugs had statistically higher levels of glucose in their blood more than the others. Although, cortisol levels were lower in the test groups compared to the control group, these differences were not significant statistically. Conclusion: The results of current study showed that both peroxinitrite and NSAIDs decrease the cortisol levels of blood. These findings can be a possible explanation for the lower levels of cortisol in the blood of patient who receive nitro glisirin as well as osteoarthritis patients that mainly take NSAIDs. In the study, the glucose levels of blood in animals given drugs were more than the control groups.