Protective effects of BPC 157 in rats with experimentally induced lower extremity ischemia-reperfusion injury.

“Protective effects of BPC 157 in rats with experimentally induced lower extremity ischemia-reperfusion injury. Yıldırım AK(1), Demirtaş H(2), Özer A(2), Arslan M(3)(4)(5). Author information: (1)Health Sciences University Gulhane Training and Research Hospital, Ankara, Turkey. (2)Department of Cardiovascular Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey. (3)Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara, Turkey. mustarslan@gmail.com. (4)Application and Research Centre for Life Sciences, Gazi University, Ankara, Turkey. mustarslan@gmail.com. (5)Centre for Laboratory Animal Breeding and Experimental Research (GÜDAM), Gazi University, Ankara, Turkey. mustarslan@gmail.com. Ischemia-reperfusion (I/R) injury remains a major complication in peripheral arterial disease, characterized by oxidative stress, inflammation, and apoptosis. Body Protection Compound-157 (BPC 157), a stable gastric pentadecapeptide, has demonstrated cytoprotective properties in multiple tissues. This study aimed to evaluate the protective effects of BPC 157 in a rat model of lower limb I/R injury. Twenty-four male Wistar albino rats were randomized into four groups (n = 6): SHAM, B (BPC 157 only), IR (I/R), and IRB (I/R + BPC 157). I/R was induced by abdominal aortic clamping for 45 min followed by 2 h of reperfusion. BPC 157 (20 µg/kg, intraperitoneal) was administered at the 45th minute of ischemia in B and IRB groups. Biochemical markers (MDA, SOD, TAS, TOS) were measured in serum. Gene expression of Il-6, Hif-1α, p53, Bcl-2, Bax, and Casp3 was assessed by qRT-PCR, while immunohistochemistry evaluated VEGF, eNOS, IL-6, and Caspase-3 expression. Histopathological changes were scored with hematoxylin-eosin and Masson's trichrome staining. I/R significantly increased MDA, TOS, p53, Bax, Casp3, Hif-1α, Il-6, and histopathological injury scores, while reducing SOD, TAS, and VEGF expression. Bcl-2 mRNA was not significantly reduced by I/R compared with SHAM; however, BPC 157 significantly increased Bcl-2 expression compared with IR. In the IRB group, BPC 157 reduced MDA and TOS, restored SOD and TAS, downregulated p53, Bax, and Casp3, reduced IL-6 and Caspase-3 immunoreactivity, and partially restored VEGF expression. Histological analysis confirmed improved muscle architecture and reduced collagen deposition in IRB compared with IR. BPC 157 appears to exert protective effects against skeletal muscle I/R injury by attenuating oxidative stress, modulating apoptosis, reducing inflammation, and supporting angiogenic activity. These findings suggest that BPC 157 may represent a potential therapeutic candidate for mitigating reperfusion injury; however, further studies with larger cohorts and dose-response evaluations are required to confirm these effects and establish clinical relevance. © 2026. The Author(s). Conflict of interest statement: Declarations. Competing interests: The authors declare no competing interests. Institutional Review Board Statement: Ethical approval for the study was obtained from the Gazi University Animal Experiments Local Ethics Committee (Ankara, Turkey; Approval number: G.Ü.ET-24.049, date: 27.05.2024). All methods were performed in accordance with relevant institutional and international guidelines and regulations, including the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, 1986) and the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals (2020). The study was conducted and reported in accordance with the ARRIVE guidelines.”