Acute and subchronic interaction between metformin and meloxicam in mice

Abstract

Acute and subchronic interaction and assessment of some biochemical parameters of metformine (antidiabetic agent) and meloxicam (nonsteroidal anti-inflammatory agent), were investigated in male Balb-C mice. Fifteen male mice were in-volved for studying acute toxicity and their interaction, further fifteen mice also were em-ployed for calculation LD50 after subchronic exposure to both medicines alone and their co-mbination, up and down method had been carried out for evaluating the LD50 after acute and subchronic exposure. Twenty male mice divided equally into four groups for studying orally subchronic exposure and assigned as, group 1(G1) 14 mg/Kg.BW metformine, group2(G2) meloxicam 0.2 mg/Kg.BW group 3(G3) combination of metformine) 14 mg/Kg-.BW metformine plus meloxicam 0.2 mg/Kg.BW group 3, while group 4 (C) dosed distilled waterand considered control group. The results revealed that LD50 of metformine, melox-icam and their combination were 1511, 343.04 and 694.5 plus 110 mg/Kg. BW respectively, while the LD50 of them after subchronic exposure were 1611, 343.03 and 897.5 plus 228.3 mg/Kg.BW respectively. Regarding to toxiclogical aspect the interaction sorts of both medicines were synergism and antagonism after acute and subchronic exposure respecti-vely. The results of subchronic exposure revealed/there were significant p<0.05 decrease in blood glucose, serum cholesterol in all treated groups, increase in triglyceride of group2, ALT and AST activity of group 2 and 3, decrease in serum uric acid of gro-up1 and 3, serum creatinine of group 2 and BUN of group3 incomparison to the cont-rol group, but the changes in the all these biochemical parameters, being in the ran-ge of the normal values regarding to literatures, except BUN in mice of group2 which exceeded. The histopathological changes in both liver and kidney could be sumarized as, monnuclear infiltration (MNCs), multiple foci of necrotic area in live of group1. Degeneration, swollen of hepatic cells and MNCs infiltration in group2.Multiple ne-crosis, severe perivascular cuffing of MNCs surrounded blood vessels in group3. The kidney lesions were represented by necrosis, inflammatory cells infiltration, nephritis, depletion of many glomerular tufts and hyaline cast filled many dilated renal tubules of group 1. Thickening of pelvis epithelium. pylitis ,atrophy of glomeruls and vacuolar degeneration in group2. Vacoular degeneration of renal epithelium, subcapsular and interlobular hemorrhage, enlargement of glomruler tuft and infiltration of MNCs in group3.