Lipid peroxidation: A mechanism involved in acute ethanol toxicity as demonstrated by in vivo pentane production in the rat

Litov, Richard E.; Irving, Dennis H.; Downey, Jeanne E.; Tappel, Al L.

doi:10.1007/bf02533677

Cited by 83 publications

(13 citation statements)

References 11 publications

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“…First, the detection of carbon-centered radicals in livers of ethanol-treated rats provides direct evidence that a free radical process has been initiated by chronic ethanol exposure. Second, because radicals of the type observed may be associated with the process of lipid peroxidation, these data provide support for the hypothesis that lipid peroxidation occurs in' liver as a result of ethanol administration (1,5,8,(25)(26)(27)(28)(29).…”

supporting

confidence: 56%

Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro.

Reinke

Lai

Dubose

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

204

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Rats fed a high-fat ethanol-containing diet for 2 weeks were found to generate free radicals in liver and heart in vivo. The radicals are believed to be carbon-centered radicals, were detected by administering spin-trapping agents to the rats, and were characterized by electron paramagnetic resonance spectroscopy. The radicals in the liver were demonstrated to be localized in the endoplasmic reticulum. Rats fed ethanol in a low-fat diet showed significantly less free radical generation. Control animals given isocaloric diets without ethanol showed no evidence of free radicals in liver and heart. When liver microsomes prepared from rats fed the high-fat ethanol diet were incubated in a system containing ethanol, NADPH, and a spin-trapping agent, the generation of 1-hydroxyethyl radicals was observed. The latter was verified by using "3C-substituted ethanol. Microsomes from animals fed the high-fat ethanol-containing diet had higher levels of cytochrome P-450 than microsomes from rats fed the low-fat ethanol-containing diet. The results suggest that the consumption of ethanol results in the production of free radicals in rat liver and heart in vivo that appear to initiate lipid peroxidation.Chronic excessive use of alcohol by humans results in liver disease (1, 2) characterized by fatty infiltration, which can lead to fibrotic degeneration and necrosis (1,3,4). However, the mechanisms leading to the development of alcoholic liver disease remain unclear. Lipid peroxidation was linked to ethanol consumption by Di Luzio and coworkers (5, 6), who reported that antioxidants prevented the development of fatty liver after a large acute dose of ethanol. Investigations by others have subsequently indicated that lipid peroxidation appears to occur in the livers of animals soon after the administration of an acute dose of alcohol. Much of the evidence for these claims has been based on the thiobarbituric acid assay for malondialdehyde in livers of animals treated with ethanol (7, 8), but increases in conjugated dienes and chemiluminescence as well as decreases in hepatic glutathione have also been reported (8). In addition, Muller and Sies (9) have reported an enhanced production of ethane and n-pentane, which are believed to be products of the peroxidative degradation of membrane lipids, during the metabolism of ethanol by perfused livers. These various findings have been interpreted as evidence that lipid peroxidation has occurred in the liver as a result of ethanol metabolism. Lipid peroxidation has also been proposed as a mechanism of ethanol-induced toxicity in the heart (10), gastric mucosa (11), and testes (12). However, the role of peroxidative events in the development of human alcoholrelated disease is highly controversial.Mechanisms that may initiate lipid peroxidation after ethanol exposure are also uncertain. Several laboratories have presented evidence that chronic ethanol feeding stimulates the production of hydroxyl radicals by liver microsomes (13,14). If this type of radical production occurs in the...

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supporting

confidence: 56%

Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro.

Reinke

Lai

Dubose

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

204

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“…More extreme changes in n-3 vs. n-6 fatty acid intake may have been necessary in order to detect a change in ethane output. We attempted to control for other factors known to influence breath alkane output such as the PUFA/saturated fatty acid ratio of the diet (39), exercise levels (44), and alcohol consumption (45,46) in order to reduce the inter-and intrasubject variability. However, unlike animal studies (43) done in a laboratory environment, this study was not performed in a clinical investigation unit, and thus strict control of these variables was not possible.…”

Section: Discussionmentioning

confidence: 99%

Lipid peroxidation during n−3 fatty acid and vitamin E supplementation in humans

Allard

Kurian²,

Aghdassi³

et al. 1997

Lipids

151

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The purpose of this study was to investigate in healthy humans the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake, alone or in combination with dL-alpha-tocopherol acetate (vitamin E) supplements on lipid peroxidation. Eighty men were randomly assigned in a double-blind fashion to take daily for 6 wk either menhaden oil (6.26 g, n-3 fatty acids) or olive oil supplements with either vitamin E (900 IU) or its placebo. Antioxidant vitamins, phospholipid composition, malondialdehyde (MDA), and lipid peroxides were measured in the plasma at baseline and week 6. At the same time, breath alkane output was measured. Plasma alpha-tocopherol concentration increased in those receiving vitamin E (P < 0.0001). In those supplemented with n-3 fatty acids, EPA and DHA increased in plasma phospholipids (P < 0.0001) and plasma MDA and lipid peroxides increased (P < 0.001 and P < 0.05, respectively). Breath alkane output did not change significantly and vitamin E intake did not prevent the increase in lipid peroxidation during menhaden oil supplementation. The results demonstrate that supplementing the diet with n-3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation.

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“…The concept of the involvement of lipid peroxidation in the hepatotoxicity of ethanol (Di Luzio, 1966, 1973Di Luzio & Stege, 1977) has recently found support with experiments with intact animals where volatile hydrocarbons were detected in the breath after an acute application of ethanol (K6ster et al, 1977;Litov et al, 1978Litov et al, , 1981Burk & Lane, 1979), using the method described by Riely et al (1974). However, Frank et al (1980) have proposed that increased exhalation of hydrocarbons upon acute doses of ethanol cannot be taken as proof for lipid peroxidation, but rather for its inhibitory effect on a specific form of cytochrome P-450 capable of metabolizing hydrocarbons that may arise from endogenous sources.…”

mentioning

confidence: 96%

Role of alcohol dehydrogenase activity and the acetaldehyde in ethanol- induced ethane and pentane production by isolated perfused rat liver

Müller¹,

Sies²

1982

Biochemical Journal

135

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The volatile hydrocarbons ethane and n-pentane are produced at increased rates by isolated perfused rat liver during the metabolism of acutely added ethanol. The effect is half-maximal at 0.5 mM-ethanol, and it is not observed when inhibitors of alcohol dehydrogenase such as 4-methyl-or 4-propyl-pyrazole are also present. Propanol, another substrate for the dehydrogenase, is also active. Increased alkane production can be initiated by adding acetaldehyde in the presence of 4-methyl-or 4-propyl-pyrazole. An antioxidant, cyanidanol, suppresses the ethanol-induced alkane production. The data obtained with the isolated organ demonstrate that products known to arise from the peroxidation of polyunsaturated fatty acids are formed in the presence of ethanol and that the activity of alcohol dehydrogenase is required for the generation of the active radical species. The mere presence of ethanol, e.g. at binding sites of special form(s) of cytochrome P-450, is not sufficient to elicit an increased production of volatile hydrocarbons by rat liver.

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Lipid peroxidation: A mechanism involved in acute ethanol toxicity as demonstrated by in vivo pentane production in the rat

Cited by 83 publications

References 11 publications

Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro.

Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro.

Lipid peroxidation during n−3 fatty acid and vitamin E supplementation in humans

Role of alcohol dehydrogenase activity and the acetaldehyde in ethanol- induced ethane and pentane production by isolated perfused rat liver

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