Oxidative Stress During Treatment With First- and Second-Generation Antipsychotics

Kropp, Stefan; Kern, Veronika; Lange, Kirsten; Degner, Detlef; Hajak, Göran; Kornhuber, Johannes; Rüther, Eckart; Emrich, H. M.; Schneider, Udo; Bleich, Stefan

doi:10.1176/jnp.17.2.227

Cited by 80 publications

(25 citation statements)

References 31 publications

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“…The level of lipid peroxidation (measured by the levels of TBARS) was significantly higher after the incubation with haloperidol than after amisulpride. These results are similar to previous results of animal studies and a few clinical observations of TBARS levels in patients treated with antipsychotics are described [42,44,45].…”

Section: Discussionsupporting

confidence: 92%

“…It should be mentioned that therapy with antipsychotic drugs may affect lipid metabolism [41]. Classical antipsychotic drugs may exhibit prooxidative effects [14,41], whereas the second generation antipsychotic drugs do not exhibit such effects, moreover they may have even antioxidative effects [14,42]. The earlier [43] and presented study also showed a significant different action of FGA (haloperidol) and SGA (amisulpride) on plasma lipid peroxidation.…”

Section: Discussionmentioning

confidence: 65%

See 1 more Smart Citation

Beta-glucan from Saccharomyces cerevisiae reduces plasma lipid peroxidation induced by haloperidol

Dietrich‐Muszalska

Olas

Kontek

et al. 2011

International Journal of Biological Macromolecules

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 65%

Beta-glucan from Saccharomyces cerevisiae reduces plasma lipid peroxidation induced by haloperidol

Dietrich‐Muszalska

Olas

Kontek

et al. 2011

International Journal of Biological Macromolecules

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“…Higher levels of lipid peroxidation products have been reported in patients treated with typical than atypical drugs (Kropp et al, 2005), but contradictory results were reported by others (Gama et al, 2006;Zhang et al, 2006a). The differing pro-oxidant potentials of the antipsychotics have been postulated as a mediating factor in the more common development of tardive dyskinesia with typical agents (Andreassen and Jorgensen, 2000).…”

Section: Clinical Studiesmentioning

confidence: 99%

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

Berk

Dean

et al. 2008

Int. J. Neuropsychopharm.

864

569

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Oxidative stress has been implicated in the pathogenesis of diverse disease states, and may be a common pathogenic mechanism underlying many major psychiatric disorders, as the brain has comparatively greater vulnerability to oxidative damage. This review aims to examine the current evidence for the role of oxidative stress in psychiatric disorders, and its academic and clinical implications. A literature search was conducted using the Medline, Pubmed, PsycINFO, CINAHL PLUS, BIOSIS Previews, and Cochrane databases, with a time-frame extending to September 2007. The broadest data for oxidative stress mechanisms have been derived from studies conducted in schizophrenia, where evidence is available from different areas of oxidative research, including oxidative marker assays, psychopharmacology studies, and clinical trials of antioxidants. For bipolar disorder and depression, a solid foundation for oxidative stress hypotheses has been provided by biochemical, genetic, pharmacological, preclinical therapeutic studies and one clinical trial. Oxidative pathophysiology in anxiety disorders is strongly supported by animal models, and also by human biochemical data. Pilot studies have suggested efficacy of N-acetylcysteine in cocaine dependence, while early evidence is accumulating for oxidative mechanisms in autism and attention deficit hyperactivity disorder. In conclusion, multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders. These data not only suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions.

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“…Ketamine, a dissociative anesthetic and an NMDA antagonist, has been shown to cause schizophrenialike symptoms in humans and is widely used in rodents to create a condition mimicking schizophrenia [28,30]. Oxidative stress has been strongly implicated in the development of schizophrenic symptoms and evidence of lipid peroxidation and protein oxidation/nitration has been found in the plasma of schizophrenic subjects [5,9,36,37]. Here we studied oxidative stress in the brain of mice treated with ketamine alone or with the antipsychotic drugs clozapine and haloperidol.…”

Section: Discussionmentioning

confidence: 99%

Brain Oxidative Stress and Neurodegeneration in the Ketamine Model of Schizophrenia during Antipsychotic Treatment: Effects of N-Acetylcysteine Treatment

Abdel-Salam¹,

El-Shamarka²,

Omara³

2018

ROS

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We aimed to investigate the effect of N-acetylcysteine (NAC) on brain oxidative stress and on the response to therapy with clozapine or haloperidol in the ketamine model of schizophrenia. Mice received intraperitoneal (i.p.) injections of either saline, ketamine (30 mg/kg), NAC (50 mg/kg), ketamine + NAC, ketamine + clozapine (1.5 mg/kg), ketamine + clozapine + NAC, ketamine + haloperidol (1.5 mg/kg), or ketamine + haloperidol + NAC daily for one week. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, and paraoxonase-1 (PON-1) activity were determined in cerebral cortex and in the rest of the brain tissue. Results indicated that: (i) treatment with only NAC had no significant effects on MDA, GSH, or PON-1 activity, but resulted in a marked decrease in nitric oxide content in both the cortex and the rest of the brain compared to the saline control group; (ii) ketamine caused a significant increase in MDA, while decreasing nitric oxide, and GSH concentrations as well as PON-1activity in both the cerebral cortex and the rest of the brain. These biochemical alterations were alleviated by NAC; (iii) in ketamine-treated mice, either clozapine or haloperidol had no significant effect on MDA or GSH levels. Nitric oxide, however, showed a significant increase by either agent. Meanwhile, PON-1 activity showed a significant increase by clozapine in the cortex but was decreased by haloperidol in both the cortex and the rest of the brain compared with the ketamine only group; (iv) NAC resulted in a significant decrease in MDA in the cortex in ketamine + haloperidol-treated mice, and markedly alleviated the decline in GSH and PON-1 activity in both the cortex and the rest of the brain tissue in ketamine + clozapine-or ketamine + haloperidol-treated groups. NAC showed variable effects on brain nitric oxide in these groups; and (v) ketamine caused neurodegeneration in the cortex and striatum changes in the form of shrunken neurons, pyknotic and apoptotic nuclei, perineuronal vacuolations, and red neurons. These pathological changes were marked after treatment with either clozapine or haloperidol but ameliorated by NAC treatment. These data indicate increased brain oxidative stress in the schizophrenia model induced by ketamine in mice and that treatment with antipsychotics impairs brain antioxidants. The study suggests a potential therapeutic benefit for NAC in alleviating brain oxidative stress, lipid peroxidation, and neurodegeneration during antipsychotic drug therapy in schizophrenia.

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Oxidative Stress During Treatment With First- and Second-Generation Antipsychotics

Cited by 80 publications

References 31 publications

Beta-glucan from Saccharomyces cerevisiae reduces plasma lipid peroxidation induced by haloperidol

Beta-glucan from Saccharomyces cerevisiae reduces plasma lipid peroxidation induced by haloperidol

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

Brain Oxidative Stress and Neurodegeneration in the Ketamine Model of Schizophrenia during Antipsychotic Treatment: Effects of N-Acetylcysteine Treatment

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