BPC 157 therapy reverses severe vascular and multiorgan failure after unilateral adrenalectomy in rats

Unilateral adrenalectomy in rats can induce severe vascular and multiorgan failure, leading to an occlusion/occlusion-like syndrome with widespread tissue damage and blood pressure dysregulation. Current therapeutic strategies often fall short in comprehensively addressing the complex interplay of vascular disturbances, oxidative stress, and organ damage that ensues. This study investigates the stable gastric pentadecapeptide BPC 157, known for its cytoprotective and vascular recovery effects, as a potential therapy to mitigate these severe systemic consequences by modulating the NO-system and oxidative stress balance.

Rats underwent unilateral adrenalectomy, and the effects were assessed at 15 min, 5 h, and 24 h post-surgery. The intervention involved administering BPC 157 at doses of 10 µg or 10 ng via the intragastric (ig) route. Researchers evaluated integrated gross and morphological changes, vascular alterations, oxidative stress parameters (e.g., malondialdehyde (MDA)), and molecular markers (e.g., NOS1-3, VEGF-A) to characterize the occlusion/occlusion-like syndrome and the therapeutic impact of BPC 157.

BPC 157 therapy demonstrated significant counteraction of lesions observed peripherally and centrally across multiple organs, including the adrenal glands, brain, heart, lung, liver, kidney, and gastrointestinal tract. It effectively reversed organ hemorrhage and thrombosis. The treatment attenuated or eliminated arrhythmias, intracranial (superior sagittal sinus), portal, and caval hypertension, alongside aortic hypotension. BPC 157 also counteracted adrenal lesions, such as lipid depletion and congestion. While cortisol values remained low, they were higher in treated animals, with a shift toward the left in adrenal compensatory weight increase. Mechanistically, BPC 157 therapy modulated the NO-system and balanced oxidative stress, leading to increased NO-level, counteraction of MDA, and upregulation of NOS1-3 and VEGF-A expression.

Significant resolution occurred via activation of collateral pathways, specifically the azygos vein (direct blood flow delivery), and the recovered peduncle of the inferior suprarenal artery and superior suprarenal vein, effectively reversing Virchow's triad circumstances and counteracting the occlusion/occlusion-like syndrome as a whole.