Investigation of the roles of glucagon-like peptide-1 agonist liraglutide-mediated anti-inflammatory actions in the analgesic activity of tramadol in A local acute inflammation model

In this project, we tested our working hypothesis that that liraglutide (LRG), a Glucagon-like peptide-1 (GLP-1) receptor agonist, can alter the efficacy of tramadol (TR), a synthetic opioid, in acute inflammatory process and may have profound potential therapeutic actions in controlling the local acute inflammation. The present project was therefore aimed to clarify the possible anti-inflammatory actions of LRG, TR or their combination treatments by examining the in CG-induced acute inflammation model in rats. In the experiments, following the intraperitoneal injections of LRG, TR or LRG+TR, the most important signs of inflammatory pain monitored by using the calibrated Von Frey filaments (for mechanical allodynia) and the cold plantar test (cold allodinia). Furthermore, edema and fever by measuring paw mass and paw temperature changes in inflamed paw of rats also evaluated. Following the tests, total anti-oxidant catalytic capacity (TAC) and total oxidant capacity (TOS) for the evaluation of oxidative stress, TNF-α and IL-10 for anti-inflammatory actions VEGF-A, TGF-β1 levels were measured by ELİSA method in samples taken from paw tissues of rats. The results showed that CG injection into the paw caused inflammation characterized by redness, swelling, heat and pain hypersensitivities. LRG, TR or LRG+TR significantly ameliorated the hypersensitivities, mechanical and cold allodynia, and decreased the edema and fever. LRG dramatically suppressed the inflammatory signs when compared to those of TR. In addition, co-administration of TR and LRG resulted in increased sensitivity. Efficacies of LRG, TR or LRG+TR on inflammatory responses changed depend on the degree of inhibition in inflammatory markers of inflamed paw. Consequently, the suppressive actions of TR, LRG or TR+LRG combination in the inflammation induced hypersensitivities, edema and fever indicates that these drugs have significant anti-inflammatory potential with anti-hypersensitivities, anti-edema and anti-pyretic effects. LRG with anti-inflammatory actions may be a highly promising options for the management of inflammatory conditions or inflammatory related various diseases.