Effect of curcumin pretreatment on brain injury induced by intestinal ischemia-reperfusion in mice

Abstract

Objective To evaluate the effect of curcumin pretreatment on brain injury induced by intestinal ischemia-reperfusion (I/R) in mice. Methods Forty-eight male C57BL/6 mice, aged 8 weeks, weighing 20-24 g, were divided into 3 groups (n=16 each) using a random number table: sham operation group (Sham group), intestinal I/R group (I/R group) and curcumin pretreatment group (CUR group). Mice were subjected to 75 min superior mesenteric artery occlusion followed by 24 h reperfusion to establish the model of brain injury induced by intestinal I/R in mice.Curcumin 200 mg/kg (in 30 ml of 10% dimethyl sulfoxide) was intraperitoneally injected at 30 min before ischemia in CUR group, while 10% dimethyl sulfoxide 30 ml was given instead of curcumin in Sham group and I/R group.Two percent Evans blue (EB) in 4 ml/kg of normal saline was injected via the caudal vein at 23 h of reperfusion, 1 h later mice were sacrificed, and hippocampi were removed for determination of EB content.Mice were sacrificed at 24 h of reperfusion, hippocampal tissues were isolated for determination of wet to dry weight ratio (W/D ratio) and cell apoptosis (by TUNEL) and for examination of the pathological changes (with a light microscope), and brain tissues were isolated for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) contents (by enzyme-linked immunosorbent assay), malondialdehyde (MDA) content (by thiobarbituric acid method), superoxide dismutase (SOD) activity (by xanthine oxidase method) and expression of caspase-3 (by Western blot). Apoptosis rate was calculated. Results Compared with Sham group, the W/D ratio of hippocampal tissues, EB content and apoptosis rate were significant increased, the contents of MDA, TNF-α and IL-6 in brain tissues were increased, SOD activity was decreased, and the expression of caspase-3 was up-regulated in I/R and CUR groups (P<0.05). Compared with I/R group, the W/D ratio of hippocampal tissues, EB content and apoptosis rate were significant decreased, the contents of MDA, TNF-α and IL-6 in brain tissues were decreased, SOD activity was increased, and the expression of caspase-3 was down-regulated (P<0.05), and the pathological changes of hippocampal tissues were significantly reduced in CUR group. Conclusion Curcumin pretreatment can reduce brain injury induced by intestinal I/R in mice, and the mechanism may be related to inhibiting inflammatory responses, lipid peroxidation and cell apoptosis. Key words: CURCUMIN; Reperfusion injury; Intestinal; Brain injuries