Exploration of combined effect of peroxisome proliferator activated receptor (PPAR) agonist and retinoic acid receptor (RAR) agonist on experimental models of inflammation in rats

Abstract

Aim Inflammation is a protective mechanism which involves multiple inflammatory mediated pathways. Synovial inflammation act as a target for various symptoms of osteoarthritis through secretion of soluble elements that while elevating and perpetuating cartilage destruction, hold the potential to be used as biomarkers. The novel investigations show chondroitin sulfate is a safe and efficacious treatment for subjects with osteoarthritis. Substitute remedies i.e. nonsteroidal anti-inflammatory medications, offer analogous pain decreasing effects, but with substantially more prolonged toxic effects. Thus, the combination study of peroxisome proliferator activated receptor (PPAR) agonist (Pioglitazone, Fenofibrate) and retinoic acid receptor (RAR) agonist (retinoic acid) was planned by using two models of inflammation carrageenan-induced inflammation and monoiodo acetate (MIA) induced osteoarthritis. Method The method involves a study of 21 days utilizing 90 animals which were divided into different groups i. e Protocol-I; Group1- Carrageenan control group, Group2- Fenofibrate (100 mg/kg), Group3- Fenofibrate (300 mg/kg), Group4- Pioglitazone (10 mg/kg), Group5- Pioglitazone (30 mg/kg), Group6- Retinoic acid (5 mg/kg), Group7- Retinoic acid (10 mg/kg), Group8- Retinoic acid (5 mg/kg) + Fenofibrate (100 mg/kg), Group9- Retinoic acid (5 mg/kg) + Pioglitazone (10 mg/kg) and Protocol-II; Goup1- Monosodium iodoactetate control (MIA), Group2- Fenofibrate (100 mg/kg), Group3- Pioglitazone (10 mg/kg), Group4- Retinoic acid (5 mg/kg), Group5- Retinoic acid (5 mg/kg) + Fenofibrate (100 mg/kg), Group6- Retinoic acid (5 mg/kg) + Pioglitazone (10 mg/kg) to study various parameters like mechanical and thermal threshold, paw volume, spontaneous and ambulatory evoked pain and histopathological studies. The data was statistically analysed using two-way ANOVA followed by Bonferroni post hoc test using p value < 0.05. Result The obtained data showed that the combination of medications has statistically increased the threshold in mechanical and thermal hyperalgesia as compared to control while the paw-volume, spontaneous pain and ambulatory evoked pain all have shown significant reduction. Even the histopathological studies showed a good healing effect in individual and combined medication. Conclusion Based on the results, it can be concluded that Retinoic Acid enhance the effect of PPAR agonist.