Lutein Protects Ischemic Skin Flaps via Antioxidant and Anti-inflammatory Mechanisms in a Rat Model of Ischemia-Reperfusion Injury

Ischemia-reperfusion injury is a well-recognized challenge in reconstructive flap surgery, often leading to partial or total tissue necrosis. In this experimental study, we aimed to evaluate the protective effects of lutein—a non-provitamin A carotenoid known for its antioxidant and anti-inflammatory actions—against ischemia-reperfusion -induced damage in a rat epigastric flap model. Sixteen Sprague-Dawley rats were randomized to receive either intraperitoneal lutein (0.5 mg/kg) or saline prior to inducing 10 hours of ischemia. Flap viability was assessed macroscopically on postoperative day 10, and biochemical and histopathological analyses were conducted to explore underlying mechanisms. Compared to controls, lutein-treated animals demonstrated significantly larger flap survival areas (21.18 ± 0.88 cm² vs. 8.42 ± 1.15 cm², p < 0.05), lower malondialdehyde and myeloperoxidase levels, and higher glutathione and nitric oxide concentrations, suggesting reduced oxidative stress and improved vascular function. Histological examination revealed less necrosis, edema, and neutrophil infiltration in the lutein group, alongside enhanced fibroblast activity, collagen deposition, and neovascularization. We also observed increased epidermal thickness and a notable rise in lymphocyte infiltration, indicating possible modulation of the adaptive immune response during repair. Taken together, our findings suggest that lutein exerts a multifaceted protective effect on ischemic flap tissue and may serve as a useful adjunct in reconstructive surgery, particularly in settings with high risk of ischemia-reperfusion injury. Given its favorable safety profile and accessibility, lutein merits further investigation in clinical studies involving human tissue transfer procedures.