The water-soluble vitamin E analogue Trolox protects against ischaemia/reperfusion damage in vitro and ex vivo. A comparison with vitamin E

We investigated the activities, both in vitro and ex vivo, of the water-soluble vitamin analogue Trolox in a model of isolated heart ischaemia-reperfusion and we compared them with those of alpha-tocopherol. Isolated rat hearts were perfused with Krebs-Henseleit solution. For in vitro experiments, the hearts were perfused with Trolox (20 mumol l(-1)) and were subsequently subjected to 20 min of global ischaemia and 40 min of post-ischaemic reperfusion. For ex vivo experiments, either Trolox or alpha-tocopherol (10 mg kg(-1)) were administered by gastric gavage 60 min before excision of the heart. Various parameters of cardiac function were evaluated and oxidative damage was assessed by TBARS production. Trolox significantly enhanced cardiac recovery after ischaemia/reperfusion, both when it was perfused in vitro and after its oral administration. Vitamin E also favourably affected cardiac recovery but did so less effectively than Trolox. Further, the production of TBARS was significantly inhibited by Trolox, suggesting that its beneficial effects are due to its antioxidant activities. In conclusion, perfusion of isolated rat hearts with low concentrations of the water-soluble vitamin E analogue Trolox effectively enhances cardiac recovery after a 20 min ischaemic period and decreases reperfusion-induced oxidative damage. Interestingly, Trolox retains its activities after oral administration. Vitamin E, when administered per os, also increases functional recovery but does so less potently than Trolox. These differential effects are likely due to the scavenging, by Trolox, of reactive oxygen species generated in the water phase. (C) 2002 Elsevier Science Ltd. All rights reserved.