Effects of haloperidol and clozapine administration on oxidative stress in rat brain, liver and serum

Andreazza, Ana C.; Barakauskas, Vilte; Fazeli, Salar; Feresten, Abigail H; Shao, Li; Wei, Vivien; Wu, Claire; Barr, Alasdair M.; Beasley, Clare L.

doi:10.1016/j.neulet.2015.02.028

Cited by 23 publications

(16 citation statements)

References 46 publications

(69 reference statements)

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“…These results seem in contrast with the results obtained by previous investigators showing that haloperidol may promote oxidative injury in animal models, based on the endogenous antioxidant effect of dopamine (Andreazza et al, 2015;JodkoPiórecka and Litwinienko, 2015). However, it seems that the improvement in the oxidant status associated with haloperidol treatment was secondary to its antiinflammatory and immunomodulatory potential.…”

Section: -Discussioncontrasting

confidence: 99%

Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats

Wahba

Messiha

Abo-Saif

2015

European Journal of Pharmacology

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Section: -Discussioncontrasting

confidence: 99%

Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats

Wahba

Messiha

Abo-Saif

2015

European Journal of Pharmacology

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“…It has been reported that lipid peroxidation was altered in rat liver and brain following antipsychotic administration in rats, moreover, APPs can also elevate lipid peroxidation in human plasma ( Dietrich-Muszalska et al, 2013 ). However, how antipsychotic work on antioxidant enzymes appears controversial and inconsistent ( Parikh et al, 2003 ; Martins et al, 2008 ; Andreazza et al, 2015 ) in rat brain tissue after antipsychotic administration. A recent meta-analysis ( Flatow et al, 2013 ) also revealed that there is no replicable and significant correlation between oxidative stress indexes and clinical features.…”

Section: Discussionmentioning

confidence: 99%

The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance

et al. 2018

Front. Pharmacol.

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Olanzapine is a widely used atypical antipsychotic medication for treatment of schizophrenia and is often associated with serious metabolic abnormalities including weight gain and impaired glucose tolerance. These metabolic side effects are severe clinical problems but the underpinning mechanism remains poorly understood. Recently, growing evidence suggests that Wnt signaling pathway has a critical role in the pathogenesis of schizophrenia and molecular cascades of antipsychotics action, of which Wnt signaling pathway key effector TCF7L2 is strongly associated with glucose homeostasis. In this study, we aim to explore the characteristics of metabolic disturbance induced by olanzapine and to elucidate the role of TCF7L2 in this process. C57BL/6 mice were subject to olanzapine (4 mg/kg/day), or olanzapine plus metformin (150 mg/kg/day), or saline, respectively, for 8 weeks. Metabolic indices and TCF7L2 expression levels in liver, skeletal muscle, adipose, and pancreatic tissues were closely monitored. Olanzapine challenge induced remarkably increased body weight, fasting insulin, homeostasis model assessment-insulin resistance index, and TCF7L2 protein expression in liver, skeletal muscle, and adipose tissues. Notably, these effects could be effectively ameliorated by metformin. In addition, we found that olanzapine-induced body weight gain and insulin resistance actively influence the expression of TCF7L2 in liver and skeletal muscle, and elevated level of insulin determines the increased expression of TCF7L2 in adipose tissue. Our results demonstrate that TCF7L2 participates in olanzapine-induced metabolic disturbance, which presents a novel mechanism for olanzapine-induced metabolic disturbance and a potential therapeutic target to prevent the associated metabolic side effects.

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“…Any therapeutic benefit from CLZ treatment, however, must take into consideration the high incidence of non-EPS side-effects associated with the drug (Andreazza et al, 2015 ; Thornton et al, 2015 ; Tse et al, 2015 ; Lee et al, 2016 ). An estimated 10–20% of eligible patients are prescribed with CLZ in the U.S., a number indicative that CLZ is vastly underutilized due to concern for its side effects (Meltzer, 2012 ; Kar et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

et al. 2018

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Background: Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these.Objective: This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment.Method: A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug*, antipsychotic*, schizophrenia, schizophren*, psychos*, psychotic*, mental ill*, mental disorder*, neuroleptic*, cardiovascular*, cardiovascular diseases, clozapine*, clozaril*, autonomic*, sympathetic*, catecholamine*, norepinephrine, noradrenaline, epinephrine, adrenaline.Results: The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports.Conclusion: The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.

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Effects of haloperidol and clozapine administration on oxidative stress in rat brain, liver and serum

Cited by 23 publications

References 46 publications

Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats

Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats

The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance

Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

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