Altering effects of caffeic acid phenethyl ester (CAPE) and ischemia/reperfusion injury: an experimental study in a rat TRAM flap model

Background Many studies have been performed since the discovery of ischemia-reperfusion injury (I/R) to find substances that reverse its effects on flaps. However, because of minor or major side effects these substances are mostly failed to be put in clinical practice. In this study, the mitigation effects of caffeic acid phenethyl ester (CAPE) were investigated for its protective effects on flap necrosis in a rat model. Methods Forty-two randomized male Sprague-Dawley rats weighing between 250 and 300 g were assigned to the regular flap (G1) (n = 14), ischemic flap (G2) (n = 14), and ischemic flap + CAPE (G3) (n = 14) groups. Bilateral pedicled TRAM flaps were designed for the first seven rats of each group,; bilateral-free TRAM flaps were designed for the remaining rats in each group and referred as subgroup 1 and 2 (S1 and S2), respectively. In G1, flaps were returned to their original locations without clamping or injection. In G2 and G3, a 2-h ischemia was performed. Before the ischemic process, intraperitoneal saline and CAPE solution was administered intraperitoneally in the second and third groups, respectively. On day 7 after the operation, all flaps were harvested and subjected to biochemical (malondialdehyde, superoxide dismutase, and catalase levels) and histological examinations (hematoxylin & eosin, Mallory-Azan, anti-VEGF, anti-BAX, anti Bcl-2, and anti-iNOS stainings), respectively. Enzyme levels and the Verhofstadt scores showed a statistically significant difference in flaps among the groups. Less injury was noted in G3 than in G2 (p < 0.01). Conclusions In this experimental model, CAPE was effective in protecting tissues against ischemia-reperfusion injury. Level of evidence: no ratable