Potencial analgésico, anti-edematogênico, antipirético e atividade ulcerogênica de fármacos anti-inflamatórios, em roedores

Abstract

Nonsteroidal anti-inflammatory drugs (NSAID) are widely using in veterinary medicine, having analgesic and anti-inflammatory activity, including reduction of oedema and antipyretic actions. They inhibit the cyclooxygenase enzime (COX). There are two isoforms of COX that are responsible for synthesis of prostaglandins. The COX I is usually a constitutive enzyme expressed in tissues. Prostaglandins, prostacyclin, and thromboxane synthesized by this enzyme are responsible for normal physiologic functions. COX II, on the other hand, is inducible and synthesized by inflammatory cells after stimulation by cytokines and other mediators of inflammation. In some tissues COX II may be constitutive as central nervous system and kidney. All NSAID can cause adverse side effects and their selective degree will be important for the ocurrence of undesirable reaction. The aim of this study was to evaluate the analgesic, antioedematogenic and antipyretic activity of some antiinflammatory used in veterinary clinics, the nonselective drugs, flunixin meglumine (FM) and ketoprofen (CT); the COX II preferential, meloxicam (MX) and carprofen (CP); and COX II selective, firocoxib, after oral administration, as well as their ulcerogenic activity in gastric mucosa, allowing a comparative analyses of their antinociceptive and/or anti-inflammatory actions and their adverse side effects, helping veterinary doctor in the choose of the drug that have better relation cost/risk/benefit of this drugs. To assess the antioedematogenic effect in croton oil-induced mice ear oedema method, the CT (ID50: 3,6 mg/kg) was the most potent drug, followed by CP and FM (ID50: 12,3 and 17,8 mg/kg, respectively). The MX and FC, despite of their effectiveness, showed low activity, didn t producing sufficient effects for determination the ID50 in maximal dose (30 mg/kg). In LPS induced fever in rats, the FC produced antipyretic activity with ID50 2,9 mg/kg, accompanied by CT, CP and FM (ID 50: 3,3; 3,6 and 4 mg/kg, respectively) and with greater dose of meloxicam (ID 50: 30 mg/kg). Evaluating the antinociceptive effect in the acetic acid-induced abdominal writhing model of analgesia in mice, the MX was the most effective drug (ID50: 0,09 mg/kg), followed by FM, FC, CP and CT (ID50: 0,4; 1,9; 2,3; 3,6, respectively), and using this ID50 in the evaluation of ulcerogenic action of this drugs in mice, the FC, FM and MX didn t induce significative gastric injury in 3o and 7o day of treatment. The CT and CP induced ulceration in 3o day, being the CT most intense. However in 7o day, we didn t notice gastric injury, suggesting that adapted gastric mucosa produces increased resistance to subsequent damage by this class of drugs. This results reveal that analgesic activity of almost all of this NSAID is independent of this antiodematogenic and antipyretic actions. The CT has similar ID50 in all pharmacological assays in this study. The gastric ulcerogenic activity has inverse ratio when compared with analgesic effects.