抄録
Background and Aims: The precise pathogenic significance of oxidative injury in the evolution of alcohol-induced liver disease is still obscure. The present report was designed to investigate whether ethanol alters the production of active oxidants and biological activities of hepatocytes. Methods: The following parameters in rat hepatocytes were investigated by using fluorescence probes in vitro and ex vivo: (1) mitochondrial membrane potential and membrane permeability transition, (2) oxygen radicals generation, (3) membrane barrier function, and (4) glutathione level. Results: Ethanol (50 mmol/l) increased oxidative stress in hepatocytes and subsequently induced an increased mitochondrial permeability transition and a decreased membrane potential. These ethanol-induced alterations were attenuated by an inhibitor of alcohol dehydrogenase and an intracellular oxidant scavenger, whereas they were enhanced by diethyl maleic acid, a glutathione depletor. Ethanol plus diethyl maleic acid but not ethanol alone increased the number of hepatocytes with membrane barrier dysfunction. A continuous infusion of ethanol (50 mmol/l) increased oxidative stress and decreased mitochondrial membrane potential in the pericentral area of isolated perfused rat liver. Conclusions: Active oxidants generated during ethanol metabolism increase mitochondrial permeability transition and modulate mitochondrial energy synthesis in hepatocytes. Reduction of glutathione level enhances mitochondrial dysfunction and impairs membrane barrier function of hepatocytes.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 1331-1343 |
| ページ数 | 13 |
| ジャーナル | Gastroenterology |
| 巻 | 112 |
| 発行部数 | 4 |
| DOI | |
| 出版物ステータス | Published - 1997 |
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ASJC Scopus subject areas
- Gastroenterology
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Oxidative stress on mitochondria and cell membrane of cultured rat hepatocytes and perfused liver exposed to ethanol. / Kurose, I.; Higuchi, H.; Kato, Shinzo; Miura, S.; Watanabe, N.; Kamegaya, Y.; Tomita, K.; Takaishi, M.; Horie, Y.; Fukuda, M.; Mizukami, K.; Ishii, H.
：: Gastroenterology, 巻 112, 番号 4, 1997, p. 1331-1343.研究成果: Article
}
TY - JOUR
T1 - Oxidative stress on mitochondria and cell membrane of cultured rat hepatocytes and perfused liver exposed to ethanol
AU - Kurose, I.
AU - Higuchi, H.
AU - Kato, Shinzo
AU - Miura, S.
AU - Watanabe, N.
AU - Kamegaya, Y.
AU - Tomita, K.
AU - Takaishi, M.
AU - Horie, Y.
AU - Fukuda, M.
AU - Mizukami, K.
AU - Ishii, H.
PY - 1997
Y1 - 1997
N2 - Background and Aims: The precise pathogenic significance of oxidative injury in the evolution of alcohol-induced liver disease is still obscure. The present report was designed to investigate whether ethanol alters the production of active oxidants and biological activities of hepatocytes. Methods: The following parameters in rat hepatocytes were investigated by using fluorescence probes in vitro and ex vivo: (1) mitochondrial membrane potential and membrane permeability transition, (2) oxygen radicals generation, (3) membrane barrier function, and (4) glutathione level. Results: Ethanol (50 mmol/l) increased oxidative stress in hepatocytes and subsequently induced an increased mitochondrial permeability transition and a decreased membrane potential. These ethanol-induced alterations were attenuated by an inhibitor of alcohol dehydrogenase and an intracellular oxidant scavenger, whereas they were enhanced by diethyl maleic acid, a glutathione depletor. Ethanol plus diethyl maleic acid but not ethanol alone increased the number of hepatocytes with membrane barrier dysfunction. A continuous infusion of ethanol (50 mmol/l) increased oxidative stress and decreased mitochondrial membrane potential in the pericentral area of isolated perfused rat liver. Conclusions: Active oxidants generated during ethanol metabolism increase mitochondrial permeability transition and modulate mitochondrial energy synthesis in hepatocytes. Reduction of glutathione level enhances mitochondrial dysfunction and impairs membrane barrier function of hepatocytes.
AB - Background and Aims: The precise pathogenic significance of oxidative injury in the evolution of alcohol-induced liver disease is still obscure. The present report was designed to investigate whether ethanol alters the production of active oxidants and biological activities of hepatocytes. Methods: The following parameters in rat hepatocytes were investigated by using fluorescence probes in vitro and ex vivo: (1) mitochondrial membrane potential and membrane permeability transition, (2) oxygen radicals generation, (3) membrane barrier function, and (4) glutathione level. Results: Ethanol (50 mmol/l) increased oxidative stress in hepatocytes and subsequently induced an increased mitochondrial permeability transition and a decreased membrane potential. These ethanol-induced alterations were attenuated by an inhibitor of alcohol dehydrogenase and an intracellular oxidant scavenger, whereas they were enhanced by diethyl maleic acid, a glutathione depletor. Ethanol plus diethyl maleic acid but not ethanol alone increased the number of hepatocytes with membrane barrier dysfunction. A continuous infusion of ethanol (50 mmol/l) increased oxidative stress and decreased mitochondrial membrane potential in the pericentral area of isolated perfused rat liver. Conclusions: Active oxidants generated during ethanol metabolism increase mitochondrial permeability transition and modulate mitochondrial energy synthesis in hepatocytes. Reduction of glutathione level enhances mitochondrial dysfunction and impairs membrane barrier function of hepatocytes.
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U2 - 10.1016/S0016-5085(97)70147-1
DO - 10.1016/S0016-5085(97)70147-1
M3 - Article
C2 - 9098019
AN - SCOPUS:0030948624
VL - 112
SP - 1331
EP - 1343
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 4
ER -