The influence of chronic ethanol feeding to rats on liver mitochondrial membrane structure and function

Hosein, E. A.; Lee, Hung; Hofmann, Ilan

doi:10.1139/o80-154

Cited by 27 publications

(8 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well established that enzyme complexes of the electron transport chain require a specific phospholipid environment for maximal function 115, 16,41). As shown in Table 6, both chenodeoxycholate and lithocholate were incorporated into mitochondrial membranes.…”

Section: Discussionmentioning

confidence: 97%

“…In this animal model, decreased metabolism of fatty acids ( 12,13) and decreased mitochondrial oxidative metabolism of succinate and P-hydroxybutyrate have been described ( 141, findings consistent with decreased activity of the mitochondrial electron transport chain. The enzyme complexes of the mitochondrial electron transport chain are located in the inner mitochondrial membrane (15), and the lipid composition of this membrane is critical for normal function of the electron transport chain (15,16). In a previous study, we hypothesized that changes in the lipid composition of the inner mitochondrial membrane induced by hepatic accumulation of potentially toxic bile acids may at least partially explain the impaired function of the electron 47 1 transport chain of liver mitochondria in rats with bile duct ligation (14).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria

et al. 1994

View full text Add to dashboard Cite

The toxicity of hydrophilic (cholate) and lipophilic (deoxycholate, chenodeoxycholate, and lithocholate) bile acids on the function of the electron transport chain was investigated in intact and disrupted rat liver mitochondria. In intact mitochondria, lipophilic bile acids used at a concentration of 100 mumol/L (0.1 mumol/mg protein) inhibited state 3 and state 3u (dinitrophenol-uncoupled) oxidation rates for L-glutamate, succinate, duroquinol or ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine as substrates. In contrast, state 4 oxidation rates and ADP/oxygen ratios were not significantly affected. At a bile acid concentration of 10 mumol/L (0.01 mumol/mg protein), the state 3 oxidation rate for L-glutamate was decreased in the presence of deoxycholate, chenodeoxycholate or lithocholate, whereas only lithocholate inhibited state 3 oxidation for succinate or duroquinol. In broken mitochondria, inhibition of oxidative metabolism was found for NADH or duroquinol as substrate in the presence of 100 mumol/L lithocholate (0.2 mumol/mg protein) and for duroquinol in the presence of 100 mumol/L chenodeoxycholate. Direct assessment of the activities of the enzyme complexes of the electron transport chain revealed decreased activities of complex I and complex III in the presence of 100 mumol/L deoxycholate or chenodeoxycholate or 10 mumol/L lithocholate. Inhibition of complex IV required higher bile acid concentrations (300 mumol/L for chenodeoxycholate or 30 mumol/L for lithocholate), and complex II was not affected. Both chenodeoxycholate and lithocholate were incorporated into mitochondrial membranes. The phospholipid content of mitochondrial membranes decreased in incubations containing 100 mumol/L (0.1 mumol/mg protein) chenodeoxycholate but was not affected in the presence of 100 mumol/L lithocholate.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria

et al. 1994

View full text Add to dashboard Cite

show abstract

“…Materials and methods. Ricin (R-60) and its A and B chains were prepared as described by Nicolson et al 12. The A chain contamination of the isolated B chain was 1% maximum, as judged from the effect on protein synthesis by a lysate of rabbit reticulocytes.…”

Section: Lstituto DI Patologia Generale Dell'universitd Di Bologna 1mentioning

confidence: 99%

Secretion of high density lipoprotein by the isolated perfused alcoholic rat liver

et al. 1982

Self Cite

View full text Add to dashboard Cite

Summary. Chronic alcohol feeding of a low fat diet for 5 weeks led to a slightly raised though statistically non-significant high density liproprotein cholesterol/apoB containing lipoprotein cholesterol ratio in both the fasting rat serum as well as the secretory products of the isolated perfused liver.Previously published epidemiological studies have convincingly established that there is a very strong negative correlation between plasma HDL cholesterol levels and the probability (risk) of developing coronary heart disease 24 h 1 (CHD) -. T e molecu ar mechanisms underlying this protective capacity of HDL are not entirely clear. However, 2 propositionsS'Ghave been made: a) HDL may facilitate reverse cholesterol transport from cells of the artery wall and b) HDL may inhibit the uptake of LDL by cells of the artery wall. Plasma HDL levels may be influenced by dietary carbohydrates and alcohol, by physical activity, some lipid-lowering drugs and endocrine factors such as sex steroids and insulin 7. Alcohol appears to play a deleterious role with respect to cardiac muscles 8, while several recent epidemiological studies suggest a protective role for alcohol via elevation of HDL on the development of CHD 9-11. It was therefore decided to examine the capacity of an isolated perfused rat liver to secrete HDL cholesterol subsequent to chronic administration of alcohol in a totally liquid low fat (5%) Metrecal diet. Materials and methods.Male Sprague-Dawley rats originally weighing 150-175 g were fed a 37% alcohol low fat (5%) totally liquid Metrecal diet for 5 weeks as previously described 12'13. Livers from control and alcoholic rats fasted 20-24 h were perfused with recirculation for 3 h according to Lee and Hosein la. Serum samples were obtained from the inferior vena cava prior to protal vein cannulation. The lipids were extracted from the serum and cell-free perfusate with chloroform-methanol (2:1) and washed by the method of Folch et al. 14. Cholesterol was determined according to Zlatkis et al. 15. ApoB-containing lipoproteins (VLDL + LDL) were isolated by ultracentrifugation as follows: the density of the liver perfusate or rat serum was raised to 1.09 g/m116,17 using solid sodium bromide. The samples were centrifuged in a Beckman SW 56 rotor at 100,000 • g for 23 h. The float containing VLDL and LDL was quantitatively removed by suction and dialyzed extensively against saline-EDTA, pH 7.4 containing 0.02% sodium azide. The total lipids of the apoB-containing liproproteins were extracted r4 and the cholesterol content determined Is. The HDL cholesterol value was calculated by difference (total cholesterol minus apoB-containing lipoprotein cholesterol).Results. Rats maintained on the 37% low fat alcohol diet gained weight at a slower rate than their sucrose pair fed 13 _+3 (7) 9 _+2 (5) HDL/(VLDL+ LDL) ratio 4.2_+0.7 (7) 3.7_+0.6 (5)Rats were fed for 5 weeks on a 37% alcohol low fat liquid Metrecal diet and the serum samples obtained after a 20-24-h fast as described in the text. Each value represents the mean_+ ...

show abstract

“…Reactive oxygen species (ROS) produced during ethanol metabolism altered mitochondrial function (Mansouri et al, 2001;Miñ ana et al, 2002), and EW increased mitochondrial permeability in response to a superoxide generator (phenazine methosulfate) and oxidative stress (French and Todoroff, 1971;Hosein et al, 1980). In addition, acute administration of ethanol (5 g/kg i.p.)…”

mentioning

confidence: 99%

Ethanol Withdrawal Provokes Opening of the Mitochondrial Membrane Permeability Transition Pore in an Estrogen-Preventable Manner

Jung

Wilson

et al. 2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

We have reported that the major endogenous estrogen, 17␤-estradiol (E2), protects against oxidative injury during ethanol withdrawal (EW) in a cultured hippocampal cell line (HT22). Here, we investigated whether the pro-oxidant nature of EW mediates opening of the mitochondrial membrane permeability transition pore (PTP) in a manner protected by E2. Excess PTP opening provokes mitochondrial membrane swelling (MMS) and the collapse of membrane potential (⌬⌿m). HT22 cells were collected at the end of ethanol exposure (100 mM) for 24 h or at 4 h of EW to assess MMS by monitoring absorbance decline at 540 nm and to assess ⌬⌿m using flow cytometry. Protective effects of E2 on PTP were compared with an antioxidant butylated hydroxytoluene (BHT) and an E2 analog, ZYC26 [(3-hydroxy-2-adamantyl(1)-4-methyl-estra-1,3,5(10)-17-one], with higher antioxidant potency than E2. To assess cellular consequences of PTP opening, effects of a PTP inhibitor (cyclosporin A) on EW-induced cell death were assessed using the calcein assay. Major findings were that: 1) EW resulted in rapid MMS and ⌬⌿m collapse; 2) cyclosporin A attenuated EW-induced cell death; and 3) E2 treatment restricted to the EW phase protected against the PTP opening more prominently than BHT and to a similar degree to ZYC26. These findings suggest that EW provokes PTP opening partly but not entirely through the pro-oxidant nature and that E2 counteracts EW-associated factors to protect against the PTP opening.

show abstract

The influence of chronic ethanol feeding to rats on liver mitochondrial membrane structure and function

Cited by 27 publications

References 2 publications

Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria

Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria

Secretion of high density lipoprotein by the isolated perfused alcoholic rat liver

Ethanol Withdrawal Provokes Opening of the Mitochondrial Membrane Permeability Transition Pore in an Estrogen-Preventable Manner

Contact Info

Product

Resources

About