N-Acetylcysteine Supplementation in an Individual With Glucose-6-Phosphate Dehydrogenase Deficiency–Associated Psychosis

Monsivais, Suzanne R.; Wisdom, Nick M.; Kruse, Jennifer L.; Davis, Michael C.

doi:10.1016/j.biopsych.2016.02.028

Cited by 5 publications

(3 citation statements)

References 11 publications

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“…Thus, NAC may serve as a potential therapy for treating hypoxia‐related endothelial dysfunction in the future. NAC supplementation to compensate G6PD deficiency have been reported in several diseases [ 25 , 32 , 47 ]. As a GSH precursor, NAC mostly functions to combat oxidative stress by increasing the levels of GSH, which could also be catalyzed by G6PD from GSSG.…”

Section: Discussionmentioning

confidence: 99%

N‐Acetylcysteine protects against cobalt chloride‐induced endothelial dysfunction by enhancing glucose‐6‐phosphate dehydrogenase activity

Yang

Zhang

et al. 2022

FEBS Open Bio

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Hypoxia‐induced endothelial dysfunction is known to be involved in the pathogenesis of several vascular diseases. However, it remains unclear whether the pentose phosphate pathway (PPP) is involved in regulating the response of endothelial cells to hypoxia. Here, we established an in vitro model by treating EA.hy926 (a hybrid human umbilical vein cell line) with cobalt chloride (CoCl 2 ; a chemical mimic that stabilizes HIF‐1α, thereby leading to the development of hypoxia), and used this to investigate the involvement of PPP by examining expression of its key enzyme, glucose‐6‐phosphate dehydrogenase (G6PD). We report that CoCl 2 induces the accumulation of HIF‐1α, leading to endothelial cell dysfunction characterized by reduced cell viability, proliferation, tube formation, and activation of cytokine production, accompanied with a significant decrease in G6PD expression and activity. The addition of 6‐aminonicotinamide (6‐AN) to inhibit PPP directly causes endothelial dysfunction. Additionally, N ‐Acetylcysteine (NAC), a precursor of glutathione, was further evaluated for its protective effects; NAC displayed a protective effect against CoCl 2 ‐induced cell damage by enhancing G6PD activity, and this was abrogated by 6‐AN. The effects of CoCl 2 and the involvement of G6PD in endothelial dysfunction have been confirmed in primary human aortic endothelial cells. In summary, G6PD was identified as a novel target of CoCl 2 ‐induced damage, which highlighted the involvement of PPP in regulating the response of endothelial cell CoCl 2 . Treatment with NAC may be a potential strategy to treat hypoxia or ischemia, which are widely observed in vascular diseases.

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Section: Discussionmentioning

confidence: 99%

N‐Acetylcysteine protects against cobalt chloride‐induced endothelial dysfunction by enhancing glucose‐6‐phosphate dehydrogenase activity

Yang

Zhang

et al. 2022

FEBS Open Bio

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“…After a year of NAC treatment, the patient showed significant clinical improvement, including the recovery of the previously reported white matter lesions in neuroimaging studies. The authors suggested that NAC effects were due to the restoration of the reduced glutathione levels associated with G6PD deficiency [20]. 19 However, there are others mechanisms through which NAC may improve the clinical manifestations of this patient.…”

Section: Glucose-6-phosphate Dehydrogenase (G6pd)mentioning

confidence: 99%

“…G6PD is the first enzyme in the pentose phosphate pathway, which reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH that is needed for many biosynthetic reactions including the replenishment of glutathione.17 In addition to acute hemolytic anaemia associated with G6PD deficiency [18], some studies have shown a high proportion of psychotic patients with this defect [19]. In fact, it has been reported that a 38-yearold man diagnosed with a nonspecific psychotic disorder associated with a G6PD deficiency showed minor clinical improvement after aripiprazole treatment [20]. After a year of NAC treatment, the patient showed significant clinical improvement, including the recovery of the previously reported white matter lesions in neuroimaging studies.…”

Section: Glucose-6-phosphate Dehydrogenase (G6pd)mentioning

confidence: 99%

N-acetylcysteine in Psychiatric Disorders: Possible Role of Cysteinet Deregulation

Martínez-Banaclocha¹

2018

INDJ

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In the last years, several clinical studies have shown the usefulness of N-acetylcysteine (NAC) in psychiatric diseases including a role in some drug abuse disorders. Although the glutathione replenishment and the antioxidant activity of NAC have been suggested as the principal mechanisms to improve such a wide range of conditions, these actions seem to be unspecific and insufficient to explain all reported effects. The present paper proposes that cysteinet (cysteine network) may be deregulated in psychiatric diseases explaining the wide-range beneficial actions of NAC supplementation.

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Glucose-6-phosphate dehydrogenase activity in bipolar disorder and schizophrenia: Relationship to mitochondrial impairment

Puthumana

Regenold

2019

Journal of Psychiatric Research

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N-Acetylcysteine Supplementation in an Individual With Glucose-6-Phosphate Dehydrogenase Deficiency–Associated Psychosis

Cited by 5 publications

References 11 publications

N‐Acetylcysteine protects against cobalt chloride‐induced endothelial dysfunction by enhancing glucose‐6‐phosphate dehydrogenase activity

N‐Acetylcysteine protects against cobalt chloride‐induced endothelial dysfunction by enhancing glucose‐6‐phosphate dehydrogenase activity

N-acetylcysteine in Psychiatric Disorders: Possible Role of Cysteinet Deregulation

Glucose-6-phosphate dehydrogenase activity in bipolar disorder and schizophrenia: Relationship to mitochondrial impairment

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