Antinociceptive and antiedematogenic activities of fenofibrate, an agonist of PPAR alpha, and pioglitazone, an agonist of PPAR gamma

Abstract

Peroxisome proliferator activated receptors (PPAR) are ligand-regulated transcription factors that control the expression of many genes. The antiinflammatory activity of fibrates, PPARalpha agonists, and thiazolidinediones, PPARgamma agonists, has been demonstrated in many in vitro and a few in vivo studies. In the present study, we evaluated the effect of acute (100 or 300 mg/kg, p.o.) or prolonged (100 or 300 mg/kg day, 7 days, p.o.) treatment with fenofibrate and acute treatment with pioglitazone (doses ranging from 1 to 50 mg/kg, i.p.), PPARalpha and PPARgamma agonists, respectively, on experimental models of nociception and edema, in order to expand the knowledge of their potential antiinflammatory activities. Fenofibrate and pioglitazone did not inhibit the nociceptive response in the hot-plate model and the first phase of formaldehyde induced nociceptive response in mice. However, treatment with pioglitazone and prolonged treatment with fenofibrate inhibited the second phase of this response. Mechanical allodynia induced by carrageenan in rats was inhibited by prolonged treatment with fenofibrate, but not by acute treatment with pioglitazone or fenofibrate. Both drugs inhibited paw edema induced by carrageenan in rats. Fenofibrate did not inhibit mechanical allodynia or paw edema induced by phorbol-12,13-didecanoate (PDD), a protein kinase C activator, in rats. Pioglitazone inhibited paw edema, but not mechanical allodynia, induced by PDD. The results represent the first demonstration of the antinociceptive and antiedematogenic activities of fenofibrate and pioglitazone and give further support to the potential use of PPAR agonists in the treatment of different inflammatory diseases.