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Titolo:
THE EFFECT OF IDEBENONE, A COENZYME-Q ANALOG, ON HYDROPHOBIC BILE-ACID TOXICITY TO ISOLATED RAT HEPATOCYTES AND HEPATIC MITOCHONDRIA
Autore:
SHIVARAM KN; WINKLHOFERROOB BM; STRAKA MS; DEVEREAUX MW; EVERSON G; MIERAU GW; SOKOL RJ;
Indirizzi:
CHILDRENS HOSP,DEPT PATHOL,SECT PEDIAT GASTROENTEROL HEPATOL & NUTR,PEDIAT LIVER CTR,BOX 290 DENVER CO 80218 CHILDRENS HOSP,DEPT PATHOL,SECT PEDIAT GASTROENTEROL HEPATOL & NUTR,PEDIAT LIVER CTR DENVER CO 80218 UNIV COLORADO,SCH MED,SECT PEDIAT GASTROENTEROL HEPATOL & NUTR DENVERCO 00000 UNIV COLORADO,SCH MED,DEPT PATHOL,PEDIAT LIVER CTR DENVER CO 80262 UNIV COLORADO,SCH MED,DEPT MED,HEPATOBILIARY RES CTR DENVER CO 80262 UNIV COLORADO,SCH MED,DEPT MED,DIV GASTROENTEROL & HEPATOL DENVER CO 80262
Titolo Testata:
Free radical biology & medicine
fascicolo: 4-5, volume: 25, anno: 1998,
pagine: 480 - 492
SICI:
0891-5849(1998)25:4-5<480:TEOIAC>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
ELECTRON-TRANSPORT CHAIN; LIPID-PEROXIDATION; BRAIN MITOCHONDRIA; LIVER-TRANSPLANTATION; HYDROGEN-PEROXIDE; COPPER OVERLOAD; OXIDANT INJURY; VITAMIN-E; CHOLESTASIS; INHIBITION;
Keywords:
CHENODEOXYCHOLIC ACID; CHOLESTASIS; LIPID PEROXIDATION; REACTIVE OXYGEN SPECIES; UBIQUINONE; ANTIOXIDANTS; FREE RADICALS; LIVER INJURY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
67
Recensione:
Indirizzi per estratti:
Citazione:
K.N. Shivaram et al., "THE EFFECT OF IDEBENONE, A COENZYME-Q ANALOG, ON HYDROPHOBIC BILE-ACID TOXICITY TO ISOLATED RAT HEPATOCYTES AND HEPATIC MITOCHONDRIA", Free radical biology & medicine, 25(4-5), 1998, pp. 480-492

Abstract

Oxidant stress induced by hydrophobic bile acids has been implicated in the pathogenesis of liver injury in cholestatic liver disorders. Weevaluated the effect of idebenone, a coenzyme Q analogue, on taurochenodeoxycholic acid (TCDC)-induced cell injury and oxidant stress in isolated rat hepatocytes and on glycochenodeoxycholic acid (GCDC)-induced generation of hydroperoxides in fresh hepatic mitochondria. Isolatedrat hepatocytes in suspension under 9% oxygen atmosphere were preincubated with 0, 50, and 100 mu mol/l idebenone for 30 min and then exposed to 1000 mu mol/l TCDC for 4 h. LDH release (cell injury) and thiobarbituric acid reactive substances (measure of lipid peroxidation) increased after TCDC exposure but were markedly suppressed by idebenone pretreatment. In a second set of experiments, the addition of 100 mu mol/l idebenone up to 3 h after hepatocytes were exposed to 1000 mu mol/lTCDC resulted in abrogation of subsequent cell injury and markedly reduced oxidant damage to hepatocytes. Chenodeoxycholic acid concentrations increased to 5.15 nmol/10(6) cells after 2 h and to 7.05 after 4 hof incubation of hepatocytes with 1000 mu mol/l TCDC, and did not differ in the presence of idebenone. In freshly isolated rat hepatic mitochondria, when respiration was stimulated by succinate, 10 mu mol/l idebenone abrogated the generation of hydroperoxides during a 90-minute exposure to 400 mu mol/l GCDC. These data demonstrate that idebenone functions as a potent protective hepatocyte antioxidant during hydrophobic bile acid toxicity, perhaps by reducing generation of oxygen free radicals in mitochondria.

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Documento generato il 29/01/20 alle ore 18:59:43