Effects of lixisenatide on acute and subacute models of inflammation in male Wistar rats.

Abstract

                Analogues of Glucagon like peptide-1 authorized for the management of diabetes mellitus type 2 have demonstrated anti-inflammatory effects. However, the effects were not studied in models of inflammation. This study aimed to assess lixisenatide’s effect on male Wistar rat’s acute and subacute inflammation models. Three groups of six animals each, weighing 180±20 g, were randomly selected. Thirty minutes after per oral administration of gum acacia, aspirin and one hour after subcutaneous lixisenatide administration, 0.05 ml of Carrageenan at 1% was injected into the sub-plantar region of hind paw at left side using normal saline. A digital plethysmograph was used to measure the volume of paw oedema in ml at 0, 0.5, 1, 2, 3, 4, and 5 h, and the increase at each time point in comparison to that at 0 h was calculated. For the subacute study, with similar grouping, a pair of 10 mg sterile cotton pellets and a pair of sterile grass-piths were implanted subcutaneously in the axilla and groin. Blood samples (5 ml) were collected after 10 days for measuring the inflammatory cytokine levels. Rats were sacrificed, grass piths and cotton pellets were collected, the dry weight was calculated using the % inhibition of granuloma; haematoxylin and eosin-stained grass piths were evaluated using ANOVA and Dunnett's test. No significant reduction in rat paw oedema, percentage inhibition of cotton pellets, or levels of inflammatory markers was observed with lixisenatide treatment. The histopathology of grass piths showed abundant fibroblasts, granulation tissue, and collagen. In both acute and subacute inflammation models, lixisenatide did not reduce inflammation significantly. Therefore, GLP-1 analogues exhibit anti-inflammatory effects owing to their hypoglycaemic action in diabetes; however, they do not possess any independent anti-inflammatory effect.