Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death

<i>Aim</i>: This study sought to clarify the therapeutic benefits and mechanisms of action of pomegranate seed oil (PSO) in instances of ischemia–reperfusion (IR) damage in the lower extremities. <i>Materials and Methods</i>: The sample size was determined, then 32 rats were...

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Main Authors: Ümmü Gülşen Bozok, Aydan İremnur Ergörün, Ayşegül Küçük, Zeynep Yığman, Ali Doğan Dursun, Mustafa Arslan
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/2/212
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author Ümmü Gülşen Bozok
Aydan İremnur Ergörün
Ayşegül Küçük
Zeynep Yığman
Ali Doğan Dursun
Mustafa Arslan
author_facet Ümmü Gülşen Bozok
Aydan İremnur Ergörün
Ayşegül Küçük
Zeynep Yığman
Ali Doğan Dursun
Mustafa Arslan
author_sort Ümmü Gülşen Bozok
collection DOAJ
description <i>Aim</i>: This study sought to clarify the therapeutic benefits and mechanisms of action of pomegranate seed oil (PSO) in instances of ischemia–reperfusion (IR) damage in the lower extremities. <i>Materials and Methods</i>: The sample size was determined, then 32 rats were randomly allocated to four groups: Control (C), ischemia–reperfusion (IR), low-dose PSO (IR + LD, 0.15 mL/kg), and high-dose PSO (IR + HD, 0.30 mL/kg). The ischemia model in the IR group was established by occluding the infrarenal aorta for 120 min. Prior to reperfusion, PSO was delivered to the IR + LD and IR + HD groups at doses of 0.15 mL/kg and 0.30 mL/kg, respectively, followed by a 120 min reperfusion period. Subsequently, blood and tissue specimens were obtained. Statistical investigation was executed utilizing Statistical Package for the Social Sciences version 20.0 (SPSS, IBM Corp., Armonk, NY, USA). <i>Results</i>: Biochemical tests revealed significant variations in total antioxidant level (TAS), total oxidant level (TOS), and the oxidative stress index (OSI) across the groups (<i>p</i> < 0.0001). The IR group had elevated TOS and OSI levels, whereas PSO therapy resulted in a reduction in these values (<i>p</i> < 0.05). As opposed to the IR group, TASs were higher in the PSO-treated groups. Histopathological analysis demonstrated muscle fiber degeneration, interstitial edema, and the infiltration of cells associated with inflammation in the IR group, with analogous results noted in the PSO treatment groups. Immunohistochemical analysis revealed that the expressions of Tumor Necrosis Factor-alpha (TNF-α), Nuclear Factor kappa B (NF-κB), cytochrome C (CYT C), and caspase 3 (CASP3) were elevated in the IR group, while PSO treatment diminished these markers and attenuated inflammation and apoptosis (<i>p</i> < 0.05). The findings demonstrate that PSO has a dose-dependent impact on IR injury. <i>Discussion</i>: This research indicates that PSO has significant protective benefits against IR injury in the lower extremities. PSO mitigated tissue damage and maintained mitochondrial integrity by addressing oxidative stress, inflammation, and apoptotic pathways. Particularly, high-dose PSO yielded more substantial enhancements in these processes and exhibited outcomes most comparable to the control group in biochemical, histological, and immunohistochemical investigations. These findings underscore the potential of PSO as an efficacious natural treatment agent for IR injury. Nevertheless, additional research is required to articulate this definitively.
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spelling doaj-art-afd2adaa0c564cae88c955f372eb177a2025-08-20T02:04:01ZengMDPI AGMedicina1010-660X1648-91442025-01-0161221210.3390/medicina61020212Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell DeathÜmmü Gülşen Bozok0Aydan İremnur Ergörün1Ayşegül Küçük2Zeynep Yığman3Ali Doğan Dursun4Mustafa Arslan5Department of Physiology, Faculty of Medicine, Ankara Medipol University, Ankara 06230, TurkeyDepartment of Anesthesiology and Reamination, Faculty of Medicine, Gazi University, Ankara 06510, TurkeyDepartment of Physiology, Faculty of Medicine, Kutahya Health Sciences University, Kutahya 43020, TurkeyDepartment of Histology and Embryology, Faculty of Medicine, Gazi University, Ankara 06500, TurkeyDepartment of Physiology, Faculty of Medicine, Atılım University, Ankara 06830, TurkeyDepartment of Anesthesiology and Reamination, Faculty of Medicine, Gazi University, Ankara 06510, Turkey<i>Aim</i>: This study sought to clarify the therapeutic benefits and mechanisms of action of pomegranate seed oil (PSO) in instances of ischemia–reperfusion (IR) damage in the lower extremities. <i>Materials and Methods</i>: The sample size was determined, then 32 rats were randomly allocated to four groups: Control (C), ischemia–reperfusion (IR), low-dose PSO (IR + LD, 0.15 mL/kg), and high-dose PSO (IR + HD, 0.30 mL/kg). The ischemia model in the IR group was established by occluding the infrarenal aorta for 120 min. Prior to reperfusion, PSO was delivered to the IR + LD and IR + HD groups at doses of 0.15 mL/kg and 0.30 mL/kg, respectively, followed by a 120 min reperfusion period. Subsequently, blood and tissue specimens were obtained. Statistical investigation was executed utilizing Statistical Package for the Social Sciences version 20.0 (SPSS, IBM Corp., Armonk, NY, USA). <i>Results</i>: Biochemical tests revealed significant variations in total antioxidant level (TAS), total oxidant level (TOS), and the oxidative stress index (OSI) across the groups (<i>p</i> < 0.0001). The IR group had elevated TOS and OSI levels, whereas PSO therapy resulted in a reduction in these values (<i>p</i> < 0.05). As opposed to the IR group, TASs were higher in the PSO-treated groups. Histopathological analysis demonstrated muscle fiber degeneration, interstitial edema, and the infiltration of cells associated with inflammation in the IR group, with analogous results noted in the PSO treatment groups. Immunohistochemical analysis revealed that the expressions of Tumor Necrosis Factor-alpha (TNF-α), Nuclear Factor kappa B (NF-κB), cytochrome C (CYT C), and caspase 3 (CASP3) were elevated in the IR group, while PSO treatment diminished these markers and attenuated inflammation and apoptosis (<i>p</i> < 0.05). The findings demonstrate that PSO has a dose-dependent impact on IR injury. <i>Discussion</i>: This research indicates that PSO has significant protective benefits against IR injury in the lower extremities. PSO mitigated tissue damage and maintained mitochondrial integrity by addressing oxidative stress, inflammation, and apoptotic pathways. Particularly, high-dose PSO yielded more substantial enhancements in these processes and exhibited outcomes most comparable to the control group in biochemical, histological, and immunohistochemical investigations. These findings underscore the potential of PSO as an efficacious natural treatment agent for IR injury. Nevertheless, additional research is required to articulate this definitively.https://www.mdpi.com/1648-9144/61/2/212apoptosisinflammationischemia–reperfusionlower extremityNF-κBoxidative stress
spellingShingle Ümmü Gülşen Bozok
Aydan İremnur Ergörün
Ayşegül Küçük
Zeynep Yığman
Ali Doğan Dursun
Mustafa Arslan
Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death
Medicina
apoptosis
inflammation
ischemia–reperfusion
lower extremity
NF-κB
oxidative stress
title Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death
title_full Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death
title_fullStr Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death
title_full_unstemmed Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death
title_short Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death
title_sort effects of pomegranate seed oil on lower extremity ischemia reperfusion damage insights into oxidative stress inflammation and cell death
topic apoptosis
inflammation
ischemia–reperfusion
lower extremity
NF-κB
oxidative stress
url https://www.mdpi.com/1648-9144/61/2/212
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