Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

Álvarez-Herrera, Samantha; Escamilla, Raúl; Medina-Contreras, Óscar; Saracco, Ricardo; Flores, Yvonne N.; Hurtado‐Alvarado, Gabriela; Maldonado-García, José Luis; Becerril-Villanueva, Enrique; Pérez‐Sánchez, Gilberto; Pavón, Lenin

doi:10.3389/fendo.2020.00195

Cited by 27 publications

(22 citation statements)

References 331 publications

(295 reference statements)

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“…Given that there is enough evidence of a link between metabolic disorders caused by clozapine and early immune responses, assessing the levels of proinflammatory cytokines may help to detect metabolic problems early (Alvarez-Herrera et al 2020). In our animal experiment, the serum level of IL-β and the expression of IL-β in pancreatic tissue were markedly enhanced after treatment with clozapine, which is in line with the results of our clinical trials.…”

Section: Discussionsupporting

confidence: 88%

Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

Zhao

Zhang

et al. 2021

Psychopharmacology

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Rationale and objective Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. Methods We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. Results Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients’ BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. Conclusion Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.

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Section: Discussionsupporting

confidence: 88%

Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

Zhao

Zhang

et al. 2021

Psychopharmacology

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“…The level of 3-hydroxymelatonin in cells is proportional to the level of oxidative stress caused by ROS [34]. Antipsychotics have been shown to increase the production of ROS in cells [35,36]. The ndings, which are consistent with and signi cantly add to previous reports of ROS-induced oxidative stress in brain ECs, could imply that chlorpromazine is involved in ROS generation, resulting in oxidative stress.…”

Section: Chlorpromazine Effects On Brain Endothelia Cellssupporting

confidence: 69%

Cell Metabolomics Responses to Chlorpromazine: Novel Insights Into Blood Brain Barrier Dysfunctionality

Ngamratanapaiboon

2021

Preprint

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Blood-brain barrier (BBB) prevents drug access and impedes therapeutic efficacy. Effective methods of modulating barrier function and resolving these difficulties are desperately needed. We hypothesized that cell metabolic adaptation significantly influences physiological and pathological barrier functionality because we were convinced that a better understanding of cell-oriented BBB responses could provide valuable insight, and because metabolic dysregulation is prominent in many vascular-related pathological processes associated with BBB disruption. Biochemical fingerprints of primary brain endothelial cells (EC) were obtained using untargeted liquid chromatography–mass spectrometry (LC-MS) metabolomic profiling during chlorpromazine treatment, at concentration similar to its measured in the serum of high dosed patients, providing a functional readout of cell status. Metabolomic analyses showed brain EC had a distinct metabolic signature. Corroborating their role in BBB and CNS protection. Surprisingly, EC largely maintained their normoxic characteristics in drug treatment situations and their profiles diverged from those of control. When examining EC reactions, tissue specificity/origin is definitely significant. With a focus on cellular metabolism, we examine how cell metabolic adaptive capabilities may influence vascular stability, as well as the prospect that modifying metabolite levels may be an efficient strategy to modulate brain EC function. Overall, this study sheds new light on cell-associated metabolic changes and serves as a valuable resource for understanding BBB modifications in drug treatment circumstances.

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“…Evidence showing the relationship between risperidone and decrease in platelet-associated antibodies titers, inhibition of phagocytosis and development of acute eosinophilic pneumonia. Furthermore, immune function pathways related to T cell maturation/differentiation were among the most heavily impacted by risperidone treatment, strongly suggesting that reduced plasma con- centrations of multiple cytokines and immune modulators is a mechanism for the risperidone induced immunosuppression [28,29]. Previous experimental evidences have established risperidone can damage to the different cells by inducing oxidative stress [10,11,24].…”

Section: Discussionmentioning

confidence: 99%

Risperidone Toxicity on Human Blood Lymphocytes in Nano molar Concentrations

et al. 2022

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Risperidone is an atypical antipsychotic drug used for the pharmacotherapy of psychiatric disorders. Some reports indicate that risperidone is toxic to various systems of the body, including the immune system. This study evaluated the toxicity effect of risperidone on human blood lymphocytes. To achieve this aim, lymphocytes were isolated using Ficoll paque plus. The results showed that risperidone (12, 24 and 48 nM) causes toxicity in human blood lymphocytes by increasing the level of intracellular reactive oxygen species (ROS), damage to lysosomal membrane, the collapse of the mitochondrial membrane potential (MMP), and increased extracellular oxidized glutathione (GSSG). Also, exposure of human blood lymphocytes to risperidone is associated with a decrease in intracellular glutathione (GSH) levels. Finally, it could be concluded that oxidative stress is one of the mechanisms of risperidone-induced toxicity in human blood lymphocytes.

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Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

Cited by 27 publications

References 331 publications

Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

Cell Metabolomics Responses to Chlorpromazine: Novel Insights Into Blood Brain Barrier Dysfunctionality

Risperidone Toxicity on Human Blood Lymphocytes in Nano molar Concentrations

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