Prevention and Treatment of Drug-Induced Liver Disease

Speeg, Kermit V; Bay, Michael

doi:10.1016/s0889-8553(21)00240-5

Cited by 20 publications

(2 citation statements)

References 151 publications

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“…N-acetylcysteine administration is currently used clinically to rapidly replete liver GSH levels following acetaminophen poisoning. 39,40 To date, there have been few clinical trials with OTC; however, animal experiments have demonstrated that OTC will replete GSH and minimize oxidative stress in several animal models of injury. 41 ± 43 It seems possible that Marburg's acute MS may be driven by a positive oxidative stress feedback loop; such a loop may be broken by administration of cysteine prodrugs.…”

Section: Discussionmentioning

confidence: 99%

Macrophages: their myelinotrophic or neurotoxic actions depend upon tissue oxidative stress

2000

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There are still questions regarding whether macrophages found in MS lesions are agents of recovery or of destruction. To address this, we examined in aggregate cultures prepared from dissociated embryonic spinal cord tissue, with or without addition of exogenous macrophages, the effect of menadione-induced oxidative stress. Similar to findings of other laboratories, we observed that in the absence of oxidative stress macrophage enrichment promoted myelinogenesis. In macrophage-poor cultures, menadione at 5 microM had very little effect upon the status of the aggregate cultures; however, increasing this to 10 and 20 microM did result in some damage to axons and myelin. By contrast, in macrophage enriched cultures, menadione at a concentration as little as 5 microM caused the complete destruction of the aggregates. We suggest that in neural tissues that have sufficiently high macrophage numbers, oxidative stress results in a positive inflammatory feedback loop that results in massive tissue destruction. We further suggest that what we see in macrophage-enriched aggregates subjected to oxidative stress may represent what happens in the Marburg-type of MS lesion.

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Section: Discussionmentioning

confidence: 99%

Macrophages: their myelinotrophic or neurotoxic actions depend upon tissue oxidative stress

2000

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“…Although studies suggest that the procysteine compound NAC, unlike OTC [80], does not readily cross the blood-brain barrier [79], it has been shown to be neuroprotective following ischemia and reperfusion [81,82] in animal models. NAC is used clinically to treat acetaminophen-induced liver damage [83].…”

Section: Cysteine Delivery Vehiclesmentioning

confidence: 99%