Abstract
Intestinal ischemia and reperfusion (IIR) is a common event in patients with acute mesenteric ischemia, intestinal obstruction, organ transplantation, and hemorrhagic and septic shock. It has been demonstrated that IIR‐induced intestinal mucosa damage may cause systemic inflammation and multiple organ failure and further lead to death. Our previous study showed that oral glutamine/citrulline and antioxidant vitamins C/E have additive effects on attenuating intestinal damage and systemic inflammation in IIR rats. Herein, we investigated the effects of these supplements on IIR‐induced immune alterations. Male Wistar rats were divided into normal rats and IIR rats that underwent intestinal ischemia for 60 min and fed with placebo, glutamine/citrulline (AA), vitamins C/E (CE), or glutamine/citrulline plus vitamins C/E (AV) at 15 minutes before and 3, 9 and 21 hr after reperfusion. After 24 hr reperfusion, IIR‐increased plasma nitrate/nitrite was significantly reversed in rats with AA and CE and IIR‐increased interleukin‐6 was reversed in rats with AA, CE, and AV. The results of two‐way ANOVA showed that CE was a main factor to reverse IIR‐altered T‐helper leukocytes, B‐leukocytes, and monocytes and to increase tumor necrosis‐factor (TNF)‐alpha production in lipopolysaccharide‐stimulated leukocytes; and AA and CE were main factors to increase granulocytes in the circulation. In concanavalin A‐ and lipopolysaccharide‐stimulated splenocytes, AA was a main factor to increase TNF‐alpha and interleukin‐4 productions, CE was a main factor to increase interleukin‐4 productions, and AA and CE have significant interactions in TNF‐alpha and IL‐4 productions as shown in the significant increases in IIR rats with AV, not with AA or CE alone. In conclusion, oral glutamine/citrulline and vitamins C/E may have synergistic effects on modulating splenocytic immune responses in intestinal ischemia and reperfusion injury. The alleviated intestinal damage and systemic inflammation and the elevated splenocytic activity reveal that oral, combined administration of glutamine, citrulline, and antioxidant vitamins C and E may have beneficial effects in patients with intestinal ischemia and reperfusion.Support or Funding InformationNSC 98‐2320‐B‐030‐003‐MY3
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