Antidote Use in the Critically Ill Poisoned Patient

Betten, David P.; Vohra, Rais; Cook, Matthew D.; Matteucci, Michael J.; Clark, Richard F.

doi:10.1177/0885066606290386

Cited by 51 publications

(29 citation statements)

References 193 publications

(243 reference statements)

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“…MB is also used to treat methemoglobinemia caused by cyanide, CO, or nitrate poisoning [135]. Recent clinical uses for MB include preventing the side effects of chemotherapy (e.g., ifosfamide-induced encaphelopathy [136]) and preventing hypotension in septic shock [137]. MB is Scheme 2: The electron transport chain (ETC) of the mitochondria.…”

Section: Clinical Uses Of Methylene Bluementioning

confidence: 99%

Protective Role of Methylene Blue in Alzheimer's Disease via Mitochondria and Cytochrome c Oxidase

Atamna

Kumar

2010

JAD

120

100

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Abstract. The key cytopathologies in the brains of Alzheimer's disease (AD) patients include mitochondrial dysfunction and energy hypometabolism, which are likely caused by the accumulation of toxic species of amyloid-β (Aβ) peptides. This review discusses two potential approaches to delay the onset of AD. The first approach is use of diaminophenothiazines (e.g., methylene blue; MB) to prevent mitochondrial dysfunction and to attenuate energy hypometabolism. We have shown that MB increases heme synthesis, cytochrome c oxidase (complex IV), and mitochondrial respiration, which are impaired in AD brains. Consistently, MB is one of the most effective agents to delay senescence in normal human cells. A key action of MB appears to be enhancing mitochondrial function, which is achieved at nM concentrations. We propose that the cycling of MB between the reduced leucomethylene blue (MBH2) and the oxidized (MB) forms may explain, in part, the mitochondria-protecting activities of MB. The second approach is use of naturally occurring osmolytes to prevent the formation of toxic forms of Aβ. Osmolytes (e.g., taurine, carnosine) are brain metabolites typically accumulated in tissues at relatively high concentrations following stress conditions. Osmolytes enhance thermodynamic stability of proteins by stabilizing natively-folded protein conformation, thus preventing aggregation, without perturbing other cellular processes. Experimental evidence suggests that the level of carnosine is significantly lower in AD patients. Osmolytes may inhibit the formation of Aβ species in vivo, thus preventing the formation of soluble oligomers. Osmolytes are efficient antioxidants that may also increase neural resistance to Aβ. The potential significance of combining MB and osmolytes to treat AD are discussed.

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Section: Clinical Uses Of Methylene Bluementioning

confidence: 99%

Protective Role of Methylene Blue in Alzheimer's Disease via Mitochondria and Cytochrome c Oxidase

Atamna

Kumar

2010

JAD

120

100

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“…22,23 Methylene blue is a reduction-oxidation agent with potent antioxidant properties, that prevents formation of mitochondrial oxygen free radicals. [24][25][26] The dye also acts as an enhancer of the electron transport chain, thereby promoting oxygen consumption.…”

Section: Introductionmentioning

confidence: 99%

Rotenone-induced nigrostriatal toxicity is reduced by methylene blue

Abdel-Salam¹,

Omara²,

Youness³

et al. 2014

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This study investigated the effect of subcutaneously injected methylene blue on oxidative stress and nigrostriatal damage induced in the rat brain by systemic rotenone injection. Rotenone 1.5 mg/kg (injected subcutaneously three times per week) was given alone or in combination with methylene blue (5, 10, or 20 mg/kg subcutaneously daily) for 2 weeks. Brain concentrations of malondialdehyde, reduced glutathione, nitric oxide (nitrite), and acetylcholinesterase, paraoxonase 1 activity, and the antiapoptotic marker Bcl-2 (B-cell lymphoma 2) were determined. Histopathology, tyrosine hydroxylase immunoreactivity, tumor necrosis factor-alpha (TNF-α), and caspase-3 immunohistochemistry were also performed. Injection of rotenone resulted in increased oxidative stress in different regions of the brain. Substantial increases in malondialdehyde (by 59.6%-77.3%) and nitric oxide (by 43.7%-58.7%) were observed in the cortex, striatum, hippocampus, and medulla of rotenone-treated rats. Meanwhile, glutathione decreased by 24.3%-59.8% in these brain regions. Rotenone administration was associated with a significant decrease in paraoxonase 1 activity in the cerebral cortex, striatum, hippocampus, medulla, midbrain, and cerebellum (by 66%-73.6%). Further, acetylcholinesterase activity decreased by 44.4% in the cortex and Bcl-2 decreased in the striatum by 33.9% after rotenone injection. Rotenone induced a marked decrease in tyrosine hydroxylase immunoreactivity and increased both TNF-α and caspase-3 immunoreactivity in the striatum. These effects of rotenone were substantially reduced by coadministration of methylene blue, which resulted in significantly decreased malondialdehyde and nitrite and increased glutathione in different regions of the brain. In addition, there was increased paraoxonase 1 and acetylcholinesterase activity in response to treatment with methylene blue. Bcl-2 levels in the striatum increased significantly after the highest dose of methylene blue. Methylene blue also significantly decreased striatal expression of TNF-α and caspase-3 (apoptosis), and the degree of neuronal degeneration and gliosis in the striatum, substantia nigra, cortex, and hippocampus. Treatment with methylene blue resulted in an increased number of tyrosine hydroxylase-positive cells in the striatum, substantia nigra, and cerebral cortex, compared with the rotenone control group. The present findings suggest that treatment with methylene blue could prevent neuronal degeneration induced by rotenone injection in the rat brain. This effect may be mediated by inhibition of oxidative stress and apoptotic markers, and by enhancement of apoptotic markers and acetylcholinesterase activity.

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“…Dihydrate crystals require higher oxalate concentrations and are indicative of an intoxication with EG. These crystals following EG ingestion can help in the diagnosis when present but are unreliable and may be absent even with high-level exposure [7]. The differential diagnoses of an increased anion gap include lactic acidosis, uraemia, ketoacidosis and intoxication with methanol, salicylate or EG.…”

Section: Discussionmentioning

confidence: 99%