Semax Peptide Shows Complex, Dose-Dependent Effects on Liver Stress in Rats

Stress, whether acute or chronic, can lead to significant physiological changes, including increased oxidative stress and potential damage to vital organs like the liver. This damage is often reflected by elevated levels of lipid peroxidation (a marker of free-radical damage) and increased activity of liver enzymes like ALT and AST (transaminases) in the blood. While peptides like ACTH-(4-7)-PGP (Semax) are known for various neuroprotective and adaptogenic properties, their specific impact on liver oxidative stress and enzyme activity under different types of physiological stress remains poorly understood.

The study revealed a complex, dose- and context-dependent effect of Semax. Across the entire dose range studied (5, 50, 150, 450 μg/kg), Semax consistently produced an antioxidant effect in hepatocytes, reducing lipid peroxidation. However, its impact on serum transaminases varied significantly: Under chronic stress conditions, administration of Semax at a high dose of 450 μg/kg significantly increased the activity of both serum ALT and AST, suggesting potential liver strain. Conversely, under acute stress conditions, a prooxidant effect was observed in the liver at a Semax dose of 150 μg/kg, contradicting its general antioxidant action. The direction of changes in ALT and AST activity also depended on the dose during acute stress: ALT activity decreased at 5 and 50 μg/kg but increased at 450 μg/kg, while AST activity was reliably increased even at the lowest dose of 5 μg/kg.