Assessment of antipsychotic-induced cytotoxic effects on isolated CD1 mouse pancreatic beta cells

Abstract

Objectives: The study aims to assess apoptosis, oxidative stress, and inflammation
as underlying diabetogenic mechanisms in isolated CD1 mouse beta-pancreatic cells
of some prescribed Antipsychotics (APs).
Methods: Three types of APs were tested in different concentrations (0.1, 1, 10, and
100 μM) on adult male CD1 mice. The cytotoxicity of the tested APs was determined
using different assays including MTT and Lactate Dehydrogenase (LDH) assays.
Oxidative stress was assessed by and measuring Reactive oxygen species (ROS)
production, lipid peroxidation, and antioxidant enzyme activities. Moreover, the effect
on the inflammatory cascade was also investigated.
Results: The tested APs were cytotoxic to beta cells and showed patterns dependent
on both concentration and exposure, with a parallel reduction in glucose-stimulated
insulin secretion of the treated cells. The APs also showed induction of oxidative stress
in the treated cells by significantly increasing the ROS, lipid peroxidation, and NRf2
gene expression, together with decreased antioxidant enzyme activities. Moreover,
APs showed significant increases in cytokines levels to their estimated IC50 levels.
The activities of caspases 3, 8, and 9 were also significantly increased in all treated
samples at their IC50s and at 10 μM concentrations of all tested APs. However, the
glutathione and inhibitors of caspase-3, IL-6, and TNF-α significantly improved GSIS
and the viability of the AP-treated cells.
Conclusion: The results suggest a significant role for apoptosis, oxidative stress,
and inflammation, in the diabetogenic effect of APs, expected role of antioxidants
and anti-inflammatory drugs as therapeutics for improving the outcome in cases of
long-term prescribed APs.

Keywords:

Antipsychotic Apoptosis Diabetes mellitus Inflammation Oxidative stress
Al Doghaither, H. A., & Elmorsy, E. M. (2023). Assessment of antipsychotic-induced cytotoxic effects on isolated CD1 mouse pancreatic beta cells. International Journal of Health Sciences, 17(4), 11–21. Retrieved from https://ijhs.qu.edu.sa/index.php/journal/article/view/8074
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Author Biography

Ekramy M. Elmorsy, Pathology Department, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia

Ekramy Mahmoud Elmorsy, MD, PhD  (Corresponding author)*

Associate Professor of Toxicology

Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Pathology Department, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia

Email: ekramyelmorsy@mans.edu.eg

Contact Number: +966501275835

ORCID: 0000-0002-7444-2499

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