Protection of Pyridoxal 5′-Phosphate against Toxicity of Acetaldehyde to Hepatocytes

Abstract

Abstract

Methods were evaluated for annulling the cytotoxicity of acetaldehyde (AcH) for isolated autologous liver cells, obtained by percutaneous liver biopsy, from cases of alcoholic hepatitis. Hepatocytes so obtained were more susceptible to the cytotoxicity of AcH than hepatocytes from normal liver, viral hepatitis, alcoholic fatty liver, and stable alcoholic cirrhosis. Benzylamine (an aldehyde buffer) and pyridoxal 5′-phosphate (PLP) counteracted the cytotoxicity of AcH in vitro; pyridoxol did not. AcH cytotoxicity was seen in liver cells from vitamin B₆deficient alcoholics with alcoholic hepatitis but was reversed when the B₆ deficiency was corrected by intramuscular administration of flushing doses of pyridoxol (150 mg daily). We suggest that in vitro, benzylamine neutralizes AcH toxicity through a Schiff-base condensation with AcH, whereas pyridoxal 5′-phosphate protects against AcH toxicity in vitro and in vivo by probably forming a Schiff base with cellular amino acids, blocking further condensation of these amino groups with AcH.