Resveratrol attenuates ischemia-reperfusion-induced leukocyte-endothelial cell adhesive interactions and prolongs allograft survival across the MHC barrier

Background: Ischemic-reperfusion (IR) injury is a multifactorial process that leads to tissue damage and rejection in composite tissue allotransplantation (CTA). Antioxidant or free radical scavenger may reduce IR injury, so the effects of resveratrol, a natural antioxidant, on amelioration of leukocyte-endothelial cell adhesive interaction and prevention of transplant rejection in CTA were investigated. Methods and Results: In a microcirculatory study, resveratrol significantly reduced the number of IR-induced leukocytes rolling, adhering, and transmigrating in the postcapillary venules of the cremaster muscle. In the CTA study using groin skin flap allotransplantation across the MHC barrier 8-11-week-old Brown Norway donors (RT1ⁿ) and 10-11-week-old Lewis recipients (RT1^l) rats were randomized into 4 groups: isograft control, allograft control, and 2 groups that received different doses of resveratrol (0.1 or 0.5 mg/kg) for 7 days. Allograft control animals rejected their allograft between 5 and 7 days postoperatively, whereas resveratrol-treated recipients had a moderate survival prolongation compared with the allograft control group. Consistent with these observations, histology results also showed reduction of lymphocytic infiltration and necrosis in resveratrol-treated subjects. Conclusion: Resveratrol treatment prolonged groin skin flap allotransplant survival in the recipient and ameliorated the leukocyte-endothelial cell adhesive interactions that may lead to attenuated and delayed rejection in CTA.