Modulation of the Oxidative Stress and ICAM-1/TLR4/NF-Κβ Levels by Metformin in Intestinal Ischemia/Reperfusion Injury in Rats.

Abstract

Metformin, a biguanide drug, is used for its antihyperglycemic effects. The purpose of the present study was to investigate the effects of metformin on the experimental model of intestinal ischemia-reperfusion (I/R) injury. Ischemia was induced by superior mesenteric artery occlusion followed by reperfusion. Metformin was administered orally by gavage at doses of 50, 100 or 200 mg/kg for one week before the surgery. Rats were divided to five groups (n = 8 for each): Sham control group; I/R control group; Metformin50 treated I/R group; Metformin100 treated I/R group; and Metformin200 treated I/R group. Tissue levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1), toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) as well as histological analysis were evaluated. Metformin treatment decreased the levels of MDA in 100 and 200 mg/kg doses besides lowering the MPO activity and ICAM-1 levels in all doses. Metformin also reduced NF-κB levels at dose of 200 mg/kg and improved histopathological scores at doses of 100 and 200 mg/kg. The treatment with metformin can prevent I/R-induced intestinal injury through down-regulating ICAM-1 and NF-κB levels, reducing oxidative stress, and lowering neutrophil accumulation. We propose that metformin could be a therapeutic agent in intestinal I/R.