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    Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death
    (MDPI, 2025) Bozok, Ummu Gulsen; Ergorun, Aydan Iremnur; Kucuk, Aysegul; Yigman, Zeynep; Dursun, Ali Dogan; Arslan, Mustafa
    Aim: 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. Materials and Methods: 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). Results: Biochemical tests revealed significant variations in total antioxidant level (TAS), total oxidant level (TOS), and the oxidative stress index (OSI) across the groups (p < 0.0001). The IR group had elevated TOS and OSI levels, whereas PSO therapy resulted in a reduction in these values (p < 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 (p < 0.05). The findings demonstrate that PSO has a dose-dependent impact on IR injury. Discussion: 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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    Article
    Citation - WoS: 8
    Citation - Scopus: 12
    Protective Effects of BPC 157 on Liver, Kidney, and Lung Distant Organ Damagein Rats with Experimental Lower-Extremity Ischemia–Reperfusion Injury
    (MDPI, 2025) Demirtas, Hueseyin; Ozer, Abdullah; Yildirim, Alperen Kutay; Dursun, Ali Dogan; Sezen, Saban Cem; Arslan, Mustafa
    Background and Objectives: Ischemia–reperfusion (I/R) injury can affect multiple distant organs following I/R in the lower extremities. BPC-157’s anti-inflammatory and free radical-neutralizing properties suggest its potential in mitigating ischemia–reperfusion damage. This study evaluates the protective effects of BPC-157 on remote organ damage, including the kidneys, liver, and lungs, in a rat model of skeletal muscle I/R injury. Materials and Methods: A total of 24 male Wistar albino rats were randomly divided into four groups: sham (S), BPC-157(B), lower extremity I/R(IR) and lower extremity I/R+BPC-157(I/RB). Some 45 min of ischemia of lower extremity was followed by 2 h of reperfusion of limbs. BPC-157 was applied to groups B and I/RB at the beginning of the procedure. After 2 h of reperfusion, liver, kidney and lung tissues were harvested for biochemical and histopathological analyses. Results: In the histopathological examination, vascular and glomerular vacuolization, tubular dilation, hyaline casts, and tubular cell shedding in renal tissue were significantly lower in the I/RB group compared to other groups. Lung tissue showed reduced interstitial edema, alveolar congestion, and total damage scores in the I/RB group. Similarly, in liver tissue, sinusoidal dilation, necrotic cells, and mononuclear cell infiltration were significantly lower in the I/RB group. Additionally, the evaluation of TAS, TOS, OSI, and PON-1 revealed a statistically significant increase in antioxidant activity in the liver, lung, and kidney tissues of the I/RB group. Conclusions: The findings of this study demonstrate that BPC-157 exerts a significant protective effect against distant organ damage in the liver, kidneys, and lungs following lower extremity ischemia–reperfusion injury in rats.
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    Article
    Protective Role of Bromelain’s Antioxidant and Anti-Inflammatory Effects in Experimental Lower Limb Ischemia-Reperfusion Injury
    (Nature Portfolio, 2025) Sezen, Saban Cem; Demirtas, Huseyin; Yildirim, Alperen Kutay; Ozer, Abdullah; Dursun, Ali Dogan; Kucuk, Aysegul; Arslan, Mustafa
    Ischemia-reperfusion (IR) injury is a multifaceted pathological process characterized by excessive oxidative stress and inflammatory responses upon restoration of blood flow. Bromelain, a proteolytic enzyme complex derived from pineapple, exhibits robust antioxidant and anti-inflammatory activities. This study aimed to evaluate the protective effects and underlying mechanisms of bromelain on oxidative stress and inflammation in an experimental rat model of lower limb ischemia-reperfusion injury. Twenty-four male Wistar Albino rats were randomly allocated into four groups: Sham-operated control (SHAM), Bromelain-only (BR), Ischemia-Reperfusion (IR), and Ischemia-Reperfusion with Bromelain treatment (IR + BR). Bromelain (40 mg/kg) was administered intraperitoneally before ischemia induction. The IR model involved 45 min of infrarenal abdominal aorta occlusion followed by 120 min of reperfusion. Oxidative biomarkers (total antioxidant status [TAS], total oxidant status [TOS], oxidative stress index [OSI]) and histopathological parameters (muscle atrophy, degeneration, leukocyte infiltration, internalization of nuclei, fragmentation, and hyalinization) were analyzed. Significant increases in muscle degeneration, leukocyte infiltration, nuclear internalization, fragmentation, and elevated oxidative stress biomarkers (increased TOS and OSI, decreased TAS) were observed in the IR group compared to controls. Bromelain treatment (IR + BR) significantly ameliorated these effects, reducing muscle tissue damage, inflammation, and oxidative imbalance compared to the untreated IR group. Bromelain effectively mitigates lower limb ischemia-reperfusion injury by reducing oxidative stress, restoring antioxidant capacity, and suppressing inflammatory responses. These protective effects suggest that bromelain holds potential as a therapeutic agent for managing oxidative and inflammatory damages associated with IR conditions, warranting further clinical investigation.