Possibilities for Cytoprotective Liver Therapy, Stable Gastric Pentadecapeptide BPC 157, and Standard Agents—A Narrative Review
Marko Sever, Anita Zenko Sever, Robert Klicek, Lucija Kralj, Marta Popovic Dolic, Kresimir Luetic, Dinko Bekic, Zeljka Belosic Halle, Mario Sucic, Suncana Sikiric, Lidija Beketic Oreskovic, Antun Bacic, Sanja Strbe, Eva Staresinic, Sven Seiwerth, Predrag Sikiric, Alenka Boban Blagaic, Ivan Dobric, Mario Staresinic, Anita SkrticCytoprotection provides a conceptual framework for the preservation and restoration of tissue integrity under conditions of noxious injury. In liver disease, however, effective protection may require more than direct limitation of hepatocellular damage, encompassing endothelial function, microcirculation, vascular homeostasis, oxidative stress, inflammation, fibrosis, and portal hemodynamics. This review examines possibilities for cytoprotective liver therapy, with particular emphasis on stable gastric pentadecapeptide BPC 157 and comparison with established or experimentally investigated agents, including N-acetylcysteine, ursodeoxycholic acid, corticosteroids, resveratrol, L-arginine, curcumin, sildenafil, VEGF-related approaches, stem cell therapies, melatonin, simvastatin, prostacyclin analogues, and coenzyme Q10. Evidence is considered across representative experimental models of acetaminophen and carbon tetrachloride hepatotoxicity, bile duct ligation, and alcohol-induced liver injury. The diversity of effective agents indicates that liver injury involves multiple interconnected pathological mechanisms and that preservation of hepatocellular integrity may be achieved through different pharmacological pathways. BPC 157 is distinguished by evidence of beneficial effects across these major models and additional vascular and occlusion/occlusion-like syndromes. In particular, reported findings indicate prevention and reversal of experimentally induced portal hypertension, including prehepatic, intrahepatic, and posthepatic disturbances, together with attenuation of hepatic congestion, thrombosis, oxidative injury, and associated multiorgan dysfunction. These findings support the concept that cytoprotection may extend from hepatoprotection to restoration of vascular and tissue homeostasis. Collectively, the available preclinical evidence supports further investigation of integrated cytoprotective strategies for liver injury. Nevertheless, experimental evidence, however extensive, does not establish clinical efficacy, and appropriately designed clinical studies remain necessary to determine therapeutic applicability in human liver disease.