BPC 157 mitigates lower limb ischemia-reperfusion injury in rats by reducing oxidative stress and inflammation

Ischemia-reperfusion (I/R) injury is a critical complication in peripheral arterial disease, leading to significant tissue damage. This injury is characterized by severe oxidative stress, systemic inflammation, and widespread apoptosis, often resulting in poor functional outcomes and potential limb loss. Current therapeutic strategies are often insufficient to fully counteract these multifaceted pathological processes. Body Protection Compound-157 (BPC 157), a stable gastric pentadecapeptide, has demonstrated broad cytoprotective, anti-inflammatory, and pro-angiogenic properties across various tissues, making it a compelling candidate for mitigating I/R-induced damage.

Researchers evaluated BPC 157's effects in a rat model of lower limb I/R injury. Twenty-four male Wistar albino rats were divided 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 the B and IRB groups. Primary endpoints included serum biochemical markers (MDA, SOD, TAS, TOS), gene expression (qRT-PCR for Il-6, Hif-1α, p53, Bcl-2, Bax, Casp3), immunohistochemistry (VEGF, eNOS, IL-6, Caspase-3), and histopathological scoring (hematoxylin-eosin, Masson's trichrome).

In the I/R group, injury significantly increased markers of oxidative stress such as MDA and TOS, while reducing antioxidant capacity (SOD, TAS). Inflammatory (Il-6, IL-6 immunoreactivity) and apoptotic (p53, Bax, Casp3, Caspase-3 immunoreactivity) pathways were also significantly upregulated, alongside increased Hif-1α expression and higher histopathological injury scores. Furthermore, VEGF expression was reduced. In the IRB group, BPC 157 treatment notably counteracted these detrimental effects. BPC 157 significantly reduced MDA and TOS, and restored SOD and TAS levels. It also downregulated p53, Bax, and Casp3 gene expression, and reduced IL-6 and Caspase-3 immunoreactivity. BPC 157 partially restored VEGF expression, indicating support for angiogenic activity. Histological analysis confirmed improved muscle architecture and reduced collagen deposition in the IRB group compared to the IR group.

BPC 157 significantly increased Bcl-2 expression compared with the IR group, despite I/R not significantly reducing Bcl-2 compared to SHAM.