Reye's syndrome: Salicylates and mitochondrial functions

Martens, Margaret E.; Lee, Chuan-Pu

doi:10.1016/0006-2952(84)90209-0

Cited by 43 publications

(10 citation statements)

References 23 publications

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“…Similar to our findings regarding jasmonates, salicylate induces permeability transition in isolated mitochondria, causing swelling and membrane depolarization. Also, these effects are inhibited by cyclosporine A, suggesting the involvement of PTPC (35)(36)(37)(38). Thus, plant stress hormones found by us to share anticancer ability (4) also share the ability to directly perturb mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Jasmonates: Novel Anticancer Agents Acting Directly and Selectively on Human Cancer Cell Mitochondria

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Jasmonates: Novel Anticancer Agents Acting Directly and Selectively on Human Cancer Cell Mitochondria

et al. 2005

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“…Salicylates have damaging effects on isolated mitochondria, causing the uncoupling of oxidative phosphorylation and swelling (13)(14)(15). Aspirin and salicylate affect mitochondrial calcium homeostasis and act synergistically with the cation to impair mitochondrial respiration and ATP synthesis (16,17).…”

mentioning

confidence: 99%

Oxidative Stress Is Responsible for Mitochondrial Permeability Transition Induction by Salicylate in Liver Mitochondria

Battaglia

Salvi

Toninello

2005

Journal of Biological Chemistry

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The interaction of salicylate with the respiratory chain of liver mitochondria generates hydrogen peroxide and, most probably, other reactive oxygen species, which in turn oxidize thiol groups and glutathione. This oxidative stress, confirmed by the prevention of action by antioxidant agents, leads to the induction of the mitochondrial permeability transition in the presence of Ca 2؉ . This phenomenon induces further increase of oxidative damage resulting in impairment of oxidative phosphorylation and ␤-oxidation, cardinal features of Reye's syndrome in the liver. Mitochondrial permeability transition induction also induces the release of cytochrome c and apoptotic inducing factor from mitochondria, suggesting that salicylate also behaves as a pro-apoptotic agent. The reactive group of salicylate for inducing oxidative stress is the hydroxyl group which, by interacting with a Fe-S cluster of mitochondrial Complex I, the so-called N-2(Fe-S) center, produces reactive oxygen species.

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“…Another effect of high-dose salicylate is to uncouple and inhibit oxidative phosphoryla tion [Martens and Lee, 1984], Both oxidative phosphorylation and much of the urea cycle take place in the mitochondria and ATP is required for urea synthesis. Valproic acid also decreases ATP levels [Kesterson et al, 1984], In this study, 2,4-dinitrophenol, the classic uncoupler of oxidative phosphoryla tion, also greatly potentiated valproate-in duced hyperammonemia and at a lower dose than required with salicylate.…”

Section: Discussionmentioning

confidence: 99%

Salicylate Potentiates Valproate-induced Hyperammonemia in the Rat

Uetrecht¹

1987

Pharmacology

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Valproic acid is known to cause an increase in blood ammonia levels in humans at the usual clinical dose. In most patients, this increase is small and asymptomatic, but in some patients the increase is larger and is associated with encephalopathy. In this study, valproate also caused a small increase in blood ammonia level (from 50 to 83 μmol/l) in Wistar rats. Salicylate potentiated this increase in blood ammonia (>210 μmol/l) when coad-ministered with valproate at a dose of salicylate which did not cause a significant increase when given alone. Other nonsteroidal anti-inflammatory drugs tested (ibuprofen and naproxen) did not potentiate valproate-induced hyperammonemia, and paracetamol actually appeared to decrease ammonia levels. The degree of hyperammonemia was dependent upon diet, and fasting decreased the level of hyperammonemia. In order to determine what component of the diet was responsible for this effect, protein, fat and carbohydrate were given by gavage, individually and also a mixture of the three. Only the mixture was able to increase the degree of hyperammonemia, even though the number of calories in the mixture and in each nutrient given individually was approximately the same. 2,4-Dinitrophenol, which like salicylate uncouples oxidative phosphorylation, potentiated valproate-induced hyperammonemia at a much lower dose than salicylate. Whether salicylate can potentiate hyperammonemia and lead to encephalopathy in some patients and therefore represents one of the risk factors for observed cases of valproate toxicity remains to be determined. Potentiation of hyperammonemia by salicylates is also consistent with the apparent association between salicylates and Reye’s syndrome which is also characterized by hyperammonemia.

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Reye's syndrome: Salicylates and mitochondrial functions

Cited by 43 publications

References 23 publications

Jasmonates: Novel Anticancer Agents Acting Directly and Selectively on Human Cancer Cell Mitochondria

Jasmonates: Novel Anticancer Agents Acting Directly and Selectively on Human Cancer Cell Mitochondria

Oxidative Stress Is Responsible for Mitochondrial Permeability Transition Induction by Salicylate in Liver Mitochondria

Salicylate Potentiates Valproate-induced Hyperammonemia in the Rat

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