Metadoxine prevents damage produced by ethanol and acetaldehyde in hepatocyte and hepatic stellate cells in culture.
Metadoxine (pyridoxine-pyrrolidone carboxylate) has been reported to improve liver function tests in alcoholic patients. In the present work we have investigated the effect of metadoxine on some parameters of cellular damage in hepatocytes and hepatic stellate cells in culture treated with ethanol and acetaldehyde. HepG2 and CFSC-2G cells were treated with 50 mM ethanol or 175 microM acetaldehyde as initial concentration in the presence or absence of 10 microg ml(-1) of metadoxine. Twenty-four hours later reduced and oxidized glutathione content, lipid peroxidation damage, collagen secretion and IL-6, IL-8 and TNF- alpha secretion were determined. Our results suggest that metadoxine prevents glutathione depletion and the increase in lipid peroxidation damage caused by ethanol and acetaldehyde in HepG2 cells. In hepatic stellate cells, metadoxine prevents the increase in collagen and attenuated TNF- alpha secretion caused by acetaldehyde. Thus, metadoxine could be useful in preventing the damage produced in early stages of alcoholic liver disease as it prevents the redox imbalance of the hepatocytes and prevents TNF- alpha induction, one of the earliest events in hepatic damage.
Gutiérrez-Ruiz
M C
MC
Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, México, D.F., Mexico. mcgr@xanum.uam.mx
Bucio
L
L
Correa
A
A
Souza
V
V
Hernández
E
E
Gómez-Quiroz
L E
LE
Kershenobich
D
D
D000079:Acetaldehyde / Q000494:pharmacology*; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D000431:Ethanol / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011736:Pyridoxine / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D004338:Drug Combinations; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D003094:Collagen; C037845:metadoxine; D005978:Glutathione; D000079:Acetaldehyde; D011736:Pyridoxine; D011761:Pyrrolidonecarboxylic Acid; D019803:Glutathione Disulfide