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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoperoxidation, a degradative process of membranous polyunsaturated fatty acids, has been suggested to represent an important mechanism in the pathogenesis of ethanol toxicity on the liver and possibly also on the brain. Catalysis by transition metals, especially iron, is involved in the biosynthesis of free radicals contributing to lipid peroxidation. Although the exact nature of the redox-active iron implicated in this catalysis is still unknown, it has been well established that lipid peroxidation can be prevented in vitro by iron chelators such as desferrioxamine. Deprivation of redox-active iron through desferrioxamine inhibits by about 50% the microsomal oxidation of ethanol in vitro and reduces very significantly in vivo the overall ethanol elimination rate in rats. Administration of desferrioxamine together with ethanol also reduces the ethanol-induced disturbances in the antioxidant defense mechanisms of the hepatocyte. It also reduces in mice both the severity of physical dependence on ethanol and lethality following the acute administration of a narcotic dose of ethanol. Chronic overloading of rats with iron results, on the opposite, in an increased rate of ethanol elimination, although alcohol dehydrogenase and catalase activities are reduced and cytochrome P-450 depleted in the liver of such iron-overloaded animals. The magnitude of the ethanol-induced increase in lipid peroxidation and decrease in the major membranous antioxidant, alpha-tocopherol, is exacerbated in iron-overloaded rats. Several disturbances of iron metabolism have been reported in human alcoholics. Their contribution to ethanol toxicity appears very likely in the case of hepatic siderosis associated with alcohol abuse. Ethanol could however disturb iron metabolism even in the absence of gross abnormalities of the total iron stores. It is suggested that ethanol intoxication could increase cellular redox-active iron, thus contributing to an enhanced steady-state concentration of reactive-free radicals. This oxidative stress would lead to lipoperoxidative damage and cellular injury.
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PMID:Involvement of iron and iron-catalyzed free radical production in ethanol metabolism and toxicity. 303 5

An acute ethanol load administered to rats results in an enhancement in lipid peroxidation in the cerebellum, a brain area which is particularly sensitive to free radical attack. The ethanol load induces also a decrease in the cerebellar concentration of the three main endogenous anti-oxidant small molecules, i.e. alpha-tocopherol, ascorbate and glutathione. These findings are highly suggestive of a cerebellar oxidative stress due to acute ethanol administration. However this administration does not enhance brain mitochondrial superoxide production as well as cerebellar mitochondrial hydrogen peroxide production. An oxidative stress could also play a role in some effects of chronic alcohol intoxication on the brain. This is particularly suggested by the beneficial effects of the administration of desferrioxamine, an iron-chelator and free radical scavenger, on physical dependence on alcohol in rodents. A speculative synthesis of the mechanisms that might be involved in such an oxidative stress on the central nervous system is presented.
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PMID:Oxidative stress from alcohol in the brain. 342 57

Male Swiss mice, when exposed to increasing concentrations of ethanol vapor for a period of 9 days, developed tolerance to as well as physical dependence on ethanol. Desferrioxamine, an iron-chelator and a lipid peroxidation inhibitor, administered to individual mice at a daily dose of 350 mg/kg body weight, caused a reduction in the degree of dependence but not of tolerance. Also, desferrioxamine protected the mice against the reduction in body weight increment observed over the inhalation period. It is suggested that desferrioxamine acts either via inhibiting the ethanol-induced lipid peroxidation, suspected to be involved in dependence, or via a different iron-sensitive mechanism.
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PMID:Reduction in severity of physical dependence on ethanol in mice caused by desferrioxamine administration. 668 7