Mitochondrial alterations in livers of Sod1−/− mice fed alcohol

Kessova, Irina G.; Cederbaum, Arthur I.

doi:10.1016/j.freeradbiomed.2007.01.044

Cited by 40 publications

(28 citation statements)

References 55 publications

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“…Sod1 −/− mice in the control environment of this study show a phenotype that parallels those previously reported: small body mass (17), high oxidative stress (17), and little difference in mitochondrial function when results are expressed per mitochondrion (28). However, for those animals housed in a more demanding territorial environment, the difference in body mass was abolished, as were some of the differences in oxidative damage markers, and impairments in mitochondrial function became apparent.…”

Section: Discussionsupporting

confidence: 88%

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Superoxide dismutase deficiency impairs olfactory sexual signaling and alters bioenergetic function in mice

Garratt¹,

Pichaud²,

Glaros

et al. 2014

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

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Oxidative stress (an overproduction of reactive oxygen species in relation to defense mechanisms) may restrict investment in life history traits, such as growth, reproduction, lifespan, and the production of sexual signals to attract mates. The constraint on sexual signaling by oxidative stress is of particular interest because it has been proposed as a mechanism ensuring that only good-quality males produce the most attractive sexual signals. Despite these predictions, evidence supporting this theory is, at best, equivocal. We used a superoxide dismutase knockout mouse to demonstrate that oxidative stress directly impairs investment in morphological (preputial glands) and molecular (major urinary proteins) components of olfactory signaling essential for mate attraction. By maintaining males in a much more competitive environment than usual for mouse laboratory experiments, we also revealed a range of phenotypes of superoxide dismutase deficiency not observed in previous studies of this mouse model. This range included impaired bioenergetic function, which was undetectable in the control environment of this study. We urge further examination of model organisms in seminatural conditions and more competitive laboratory environments, as important phenotypes can be exposed under these more demanding conditions.L ife history theory is based on the premise that physiological constraints limit investment in life history components. These constraints are expected to generate the negative correlations commonly observed between these traits on an interspecies level (1). Within species, individuals also differ in their capacity to invest in different traits (2), although the physiological causes of this variation remain largely elusive.Oxidative stress occurs as a consequence of an overproduction of reactive oxygen species (ROS) in relation to defense mechanisms (3). Because ROS are produced as a by-product of oxidative phosphorylation, investment in energetically demanding life history traits has been predicted to increase oxidative stress, which may then constrain investment in other areas (4, 5). Ecological research in wild animals has provided correlative evidence for a link between oxidative stress and investment in traits, such as growth (6), reproduction (7,8), and lifespan (7). Early evidence linking oxidative stress to variation in lifespan within (9) and between species (10) led to the development of genetically modified antioxidant enzyme knockout animals, allowing precise tests of the effects of these pathways on lifespan under controlled laboratory conditions (11). These tests concluded that oxidative stress does not play a major role in governing the lifespan of laboratory animals (11).As in the case of lifespan, sexual signals show considerable among-individual variation and can correlate with oxidative stress. Sexual signals are often condition-dependent in expression, such that only good-quality signalers express the largest or most elaborate sexual signals (12). These signaling systems only evolve and rem...

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Section: Discussionsupporting

confidence: 88%

“…2C) (18); aconitase activity is greatly decreased in the liver (Fig. 2D) (28), indicating increased oxidative damage; and oxidative damage to lipids is elevated in muscle (Fig. 2H) (17).…”

Section: Resultsmentioning

confidence: 99%

Superoxide dismutase deficiency impairs olfactory sexual signaling and alters bioenergetic function in mice

Garratt¹,

Pichaud²,

Glaros

et al. 2014

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

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“…Mitochondria in ethanol-fed Sod1 -/-mice exhibit elevated levels of Bax, Bak and Bcl-xL. Immunoprecipitation studies revealed an increased association of Bax and Bak (22). In particular, Bax translocates from the cytosol to mitochondria during acute ethanol-induced apoptosis of rat hepatocytes, which results in oxidative stress.…”

Section: Free Form Bound Form Total ---------------------------------mentioning

confidence: 97%

The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats

Yoo

Jung²,

Kang³

et al. 2011

Int J Mol Med

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Abstract. In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pretreatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.

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“…Interestingly, administration of antioxidants, such as ebselen, vitamin E, superoxide dismutase (SOD), and precursors of GSH prevented alcohol-induced hepatic damage in rats [8]. Since ethanol-induced liver injury was linked to oxidative stress, Cederbaum and co-workers [13,14] investigated the effect of a compromised antioxidant defense system, copper-zinc SOD1 knockout mice, in an alcohol-induced hepatic damage model. A moderate ethanol consumption induced oxidative stress and liver damage in these mice, indicating that compromised antioxidant defense exacerbates alcohol liver damage.…”

Section: Alcoholic Liver Disease and Free Radicalsmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B 1 consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-pbenzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.

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Mitochondrial alterations in livers of Sod1−/− mice fed alcohol

Cited by 40 publications

References 55 publications

Superoxide dismutase deficiency impairs olfactory sexual signaling and alters bioenergetic function in mice

Superoxide dismutase deficiency impairs olfactory sexual signaling and alters bioenergetic function in mice

The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats

Role of free radicals in liver diseases

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