Pathologic Changes in a Rabbit Model of Reye's Syndrome

Trauner, Doris A.

doi:10.1203/00006450-198211000-00010

Cited by 24 publications

(7 citation statements)

References 10 publications

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“…Moreover, the depletion ofthe intramitochondriallevels of acetyl CoA and acid-soluble CoA may inhibit several mitochondrial enzyme activities (3). Trauner (21) reported that a continuous infusion of octanoate can induce pathologic abnormalities in the rabbit similar to those observed in patients with RS. Octanoate is a potent un coupler of oxidative phosphorylation (22,23).…”

Section: Discussionmentioning

confidence: 97%

Inhibition of Mitochondrial Functions by Margosa Oil: Possible Implications in the Pathogenesis of Reye's Syndrome

et al. 1987

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ABSTRACf. Margosa oil (MO), a fatty acid-rich extract of the seeds ofthe neem tree and a reported cause of Reye's syndrome, has been used in the induction of an experimental model of Reye's syndrome in rats. It has been reported that MO causes a decrease in in vivo mitochondrial enzyme activity similar to that seen in Reye's syndrome. We have attempted to uncover some of the biochemical mechanisms of MO's toxicity by examining its effect in vitro on isolated rat liver mitochondria . Male rat liver mitochondria were isolated by centrifugation; oxygen uptake, reduced forms of cytochrome b, c + c., a + a3, and flavoprotein, intramitochondrial concentrations of acetyl coA, acid-soluble coA, acid-insoluble coA, and ATP content were measured after incubation with and without MO. Our results reveal that MO is a mitochondrial uncoupler. State 4 respiration was increased while the respiratory control ratio was decreased. The Intramitochondrial content of ATP was also decreased . There were substantial changes in the reduction of the respiratory chain components after incubation of mitochondria with MO. This decelerative effect on mitochondrial electron transport was alleviated by the addition of coenzyme Q and/or carnitine. These effects of MO on mitochondrial respiration may be due to changes in fatty acid metabolism caused by MO as MO caused a shift in the proportion of acid-soluble or acid-insoluble coA esters. Supplementary therapy with L-carnitine and coenzyme Q may be useful in the management of MO-induced Reye's syndrome. (Pediatr Res 22: 184-187,1987) Abbreviations MO, margosa oil RS, Reye's syndrome CoQ, coenzyme Q RCR, respiratory control ratio biochemical evidence imply that in RS the mitochondrion is the major site of insult (3). Plasma from RS patients induce respiratory inhibition of isolated rat liver mitochondria (4). Similar effects have been reported with salicylates and salicyl compounds which are known to be associated with RS (5). Although there are several reports relating to the production of Reye-like hepatic mitochondrial enzyme deficits in the rat by MO there is no report on the in vitro effects of MO on the functions of isolated liver mitochondria (6, 7). Therefore , we designed this study to evaluate the effects of MO on isolated rat liver mitochondrial functions, and to determine ifthe effects ofMO could bereversed by D,L-carnitine or coenzyme Q.In view of the fact that major constituents of MO are longand medium-chain fatty acids (8), it appears likely that these fatty acids may be involved in the mechanism of the toxicity of MO. Recentl y, secondary carnitine deficiency has been reported in several inherited metabolic diseases (9) and RS (10). Since Lcarnitine serves not only as a vehicle of fatty acid transport into mitochondria but enhances regeneration of free CoA-SH in mitochondria (II), it may relieve the toxicity of MO on mitochondria if MO disrupts mitochondrial functions in a manner similar to that offatty acids. On the other hand, M0 also contains other mitochondrial toxins such...

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Section: Discussionmentioning

confidence: 97%

Inhibition of Mitochondrial Functions by Margosa Oil: Possible Implications in the Pathogenesis of Reye's Syndrome

et al. 1987

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“…Octanoic acid had previously received attention as a putative cause of brain edema in Reye's syndrome. 45 Its role in ALF is uncertain.…”

Section: Synergismmentioning

confidence: 99%

Pathogenesis of Hepatic Encephalopathy in Acute Liver Failure

Vaquero

Chung²,

Cahill³

et al. 2003

Semin Liver Dis

137

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Hepatic encephalopathy (HE) in acute liver injury signifies a serious prognosis. Brain edema and intracranial hypertension are major causes of death in this syndrome. Comparison of HE in acute liver failure (ALF) with that of cirrhosis allows recognition of important differences and similarities. A key role for ammonia in the pathogenesis of both HE and brain edema is now firmly supported by clinical and experimental data. Additional factors, such as infection, products of the necrotic liver, and synergistic toxins, may contribute to an altered mental state. A low plasma osmolarity, high temperature, and both high and low arterial pressure may affect brain water content. A combined derangement of cellular osmolarity coupled with cerebral hyperemia can explain the development of brain edema in ALF. Increasingly, study of the mechanisms responsible for brain swelling provides critical information for understanding the pathogenesis of HE.

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“…Table 3 The 1985Cm&r, 1982Ekmrgeolset al, 1971Glasgow and chase, 1975Hart et al, 1989Sinnxihet al, 1985Trauner, 1982Trauner and Adams, 1981Kang et al, 1982Davis, 1986Brownstem et al, 1984 Hyperammonemia/FluB nuclei, and satellitosis. Systemically, significant serum changes include hypoglycemia, increased free fatty acids and transaminase activities, and decreased phospholipids.…”

Section: Aflatoxinmentioning

confidence: 99%