Aims: Excessive alcohol consumption induces hepatic injury and promotes lipid accumulation, events involved in the pathogenesis of serious conditions such as alcoholic liver disease (ALD). Thus, protection of hepatocytes against alcohol-induced death is considered to be a critical approach to prevent development of liver disease. Substance P (SP) is capable of promoting cell proliferation and blocking cell death under diverse stresses, leading to beneficial effects in severe diseases, and is therefore likely to have a therapeutic application in hepatic injury.
Main methods: To assess its effects on ethanol-induced hepatic damage in vitro and in vivo, SP was administered to ethanol-treated hepatocytes and a mouse model of this condition, respectively. The effect of SP was assessed based on cell viability, apoptosis, and Akt/GSK-3β signaling, and mouse liver histology and serum biochemical parameters.
Key findings: SP was found to prevent hepatocyte death due to ethanol-induced oxidative stress by upregulating Akt/GSK-3β activation in vitro. In vivo, ethanol treatment elevated levels of serum alanine transaminase and also increased the number of apoptotic cell, exhibiting lipid accumulation in liver tissue, effects that were entirely negated by SP treatment. Taken together, our results revealed that SP is able to block hepatic damage due to ethanol-induced oxidative stress and exerts therapeutic effects in liver disease, including ALD. Our findings identify SP treatment as a potential therapy for hepatic damage.
Keywords: Alcohol; Hepatotoxicity; Oxidative stress; Substance P.
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