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

Background 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-...

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Main Authors: Ovunc Akdemir, Atilla Eyuboglu, Emel Oyku Cetin, Yigit Uyanikgil
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Journal of Investigative Surgery
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Online Access:https://www.tandfonline.com/doi/10.1080/08941939.2025.2528341
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author Ovunc Akdemir
Atilla Eyuboglu
Emel Oyku Cetin
Yigit Uyanikgil
author_facet Ovunc Akdemir
Atilla Eyuboglu
Emel Oyku Cetin
Yigit Uyanikgil
author_sort Ovunc Akdemir
collection DOAJ
description Background 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.Methods Sixteen Sprague-Dawley rats were randomized to receive either intraperitoneal lutein (0.5 mg/kg) or saline prior to inducing 10 h of ischemia. Flap viability was assessed macroscopically on postoperative day 10, and biochemical and histopathological analyses were conducted to explore underlying mechanisms.Results 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 levels (p < 0.01) and myeloperoxidase levels (p < 0.05), and higher glutathione (p < 0.05) and nitric oxide concentrations (p < 0.01), 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. Additionally, increased epidermal thickness and a notable rise in lymphocyte infiltration indicated the potential modulation of the adaptive immune response during repair.Conclusion 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 safety and supplement status, these preclinical findings support further exploration in human studies.
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spelling doaj-art-7632fd2a846e4e678d7a8a582b0fc4f12025-08-20T03:16:41ZengTaylor & Francis GroupJournal of Investigative Surgery0894-19391521-05532025-12-0138110.1080/08941939.2025.2528341Lutein Protects Ischemic Skin Flaps via Antioxidant and Anti-Inflammatory Mechanisms in a Rat Model of Ischemia-Reperfusion InjuryOvunc Akdemir0Atilla Eyuboglu1Emel Oyku Cetin2Yigit Uyanikgil3Department of Plastic, Aesthetic and Reconstructive Surgery, Istanbul Aydin University, Istanbul, TurkeyDepartment of Plastic, Aesthetic and Reconstructive Surgery, Istanbul Arel University, Istanbul, TurkeyDepartment of Biopharmaceutics and Pharmacokinetics, Ege University, Izmir, TurkeyDepartment of Histology and Embryology, Ege University, Izmir, TurkeyBackground 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.Methods Sixteen Sprague-Dawley rats were randomized to receive either intraperitoneal lutein (0.5 mg/kg) or saline prior to inducing 10 h of ischemia. Flap viability was assessed macroscopically on postoperative day 10, and biochemical and histopathological analyses were conducted to explore underlying mechanisms.Results 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 levels (p < 0.01) and myeloperoxidase levels (p < 0.05), and higher glutathione (p < 0.05) and nitric oxide concentrations (p < 0.01), 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. Additionally, increased epidermal thickness and a notable rise in lymphocyte infiltration indicated the potential modulation of the adaptive immune response during repair.Conclusion 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 safety and supplement status, these preclinical findings support further exploration in human studies.https://www.tandfonline.com/doi/10.1080/08941939.2025.2528341Luteinischemia-reperfusion injuryflap surgeryantioxidant therapytissue regeneration
spellingShingle Ovunc Akdemir
Atilla Eyuboglu
Emel Oyku Cetin
Yigit Uyanikgil
Lutein Protects Ischemic Skin Flaps via Antioxidant and Anti-Inflammatory Mechanisms in a Rat Model of Ischemia-Reperfusion Injury
Journal of Investigative Surgery
Lutein
ischemia-reperfusion injury
flap surgery
antioxidant therapy
tissue regeneration
title Lutein Protects Ischemic Skin Flaps via Antioxidant and Anti-Inflammatory Mechanisms in a Rat Model of Ischemia-Reperfusion Injury
title_full Lutein Protects Ischemic Skin Flaps via Antioxidant and Anti-Inflammatory Mechanisms in a Rat Model of Ischemia-Reperfusion Injury
title_fullStr Lutein Protects Ischemic Skin Flaps via Antioxidant and Anti-Inflammatory Mechanisms in a Rat Model of Ischemia-Reperfusion Injury
title_full_unstemmed Lutein Protects Ischemic Skin Flaps via Antioxidant and Anti-Inflammatory Mechanisms in a Rat Model of Ischemia-Reperfusion Injury
title_short Lutein Protects Ischemic Skin Flaps via Antioxidant and Anti-Inflammatory Mechanisms in a Rat Model of Ischemia-Reperfusion Injury
title_sort lutein protects ischemic skin flaps via antioxidant and anti inflammatory mechanisms in a rat model of ischemia reperfusion injury
topic Lutein
ischemia-reperfusion injury
flap surgery
antioxidant therapy
tissue regeneration
url https://www.tandfonline.com/doi/10.1080/08941939.2025.2528341
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AT atillaeyuboglu luteinprotectsischemicskinflapsviaantioxidantandantiinflammatorymechanismsinaratmodelofischemiareperfusioninjury
AT emeloykucetin luteinprotectsischemicskinflapsviaantioxidantandantiinflammatorymechanismsinaratmodelofischemiareperfusioninjury
AT yigituyanikgil luteinprotectsischemicskinflapsviaantioxidantandantiinflammatorymechanismsinaratmodelofischemiareperfusioninjury