Effects of leptin on intestinal ischemia-reperfusion injury

Many clinical conditions such as shock, sepsis, mesenteric thrombus, necrotising enterocolitis and bowel transplantation can cause intestinal ischemia reperfusion (IR) injury. Reperfusion of ischemic tissue leads to a sequence of events that, paradoxically, injure tissues. The injury produced by reperfusion can be more severe than the injury induced by ischemia . A possible cause of IR injury is attributed to oxygen free radicals. These radicals which are generated during reperfusion period are responsible for tissue injury and distant organ disfunction. Leptin is the product of obese gene and secreted mainly by adipose tissue. Besides tat tissue, the presence of leptin was detected in the other tissues including gastrointestinal system. Leptin plays important roles in many physiologic and pathologic conditions. it has antiinflammatory effects and stimulate nitric oxide (NO) production. This study was designed to determine effects of leptin on intestinal IR injury. Thirty rats were divided into 3 groups each containing ten rats: Group A (IR group), group B (IR+leptin group) and group C (sham group). Rats were anesthetised using intraperitoneal ketamine (50 mg/kg). A midline laparotomy was made, the small intestine was reflected to the left, and the superior mesenteric artery was occluded with an atraumatic clip. The rats were subjected to superior mesenteric artery occlusion for 1 hour. The intestine was replaced into the peritoneal cavity for the duration of the ischemic period. After 1 hour of intestinal ischemia, the clip was removed, allowing reperfusion. The sham operation involved the same technique and exposure, without the clipping of the superior mesenteric artery. in group B, 100 μg/kg leptin was given subcutanously 30 minutes before reperfusion. in group A and C, 0.1 mi saline was injected. 4 hours after reperfusion, 3 mi of blood was drawn for detection of serum NO and malondialdehyde (MDA) levels. A part of terminal ileum were also harvested for histopathological examination and tissue NO and MDA measurements. The results were compared statistically. in group A, serum and tissue MDA levels were significantly decreased; and NO levels were significantly increased compared with sham group (p<0.05). in sham group, histopathologic injury decreased compared with group A. in group B (IR+leptin group), serum and tissue MDA levels were significantly decreased (p<0.05); but serum and tissue NO levels were significantly increased compared with group A (p<0.05). Histopathologic injury is significantly decreased in leptin treated group compared with group A (p<0.05). The results of the present study demonstrated that leptin decreases intestinal IR injury by stimulating NO release.