Neurotoxicity of Isotretinoin in Mice: Behavioral and Tissue Neurological Function Assessment

Articles in Press

Document Type : Original Articles

Authors

1 Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq

2 Al Nour University College, Mosul, Iraq.

3 Department of Anesthesiology, Medical Technical Institute, Northern Technical University, Mosul, Iraq.

Abstract

Background: Isotretinoin is used to treat some skin disorders in dogs and cats by reducing the size and activity of their sebaceous glands, although it may have some neurobehavioral side effects. Objective: To evaluate isotretinoin's effects on the brain and neurotransmitters, as well as its impact on neurobehavior and motor activity. Methods: A total of 15 mice were arranged into 3 groups: the 1st group was a control, the 2nd group received 125 mg/kg isotretinoin, and the 3rd group received 250 mg/kg orally. Results: The LD50 for isotretinoin is 4841.2 mg/kg. The neurobehavioral measurements of mice reveal significant effects on changes in open field activity, time spent in dark areas, and negative geotaxis behaviors across different dosage levels of isotretinoin. Both doses of isotretinoin 125 and 250 mg/kg result in significant alterations in serotonin levels. Mice treated with isotretinoin at 125 mg/kg exhibit a decrease in serotonin levels compared to the control group. Both doses of isotretinoin result in significant changes in acetylcholine levels. Isotretinoin at 125 mg/kg shows a slight increase in acetylcholine. The data indicate that there is a significant increase in COMT enzyme. Histopathological study in the brain revealed that 125 mg/kg of isotritinoin showed mild vacuolization, blood vessel congestion, and mild perivascular edema. High-dose 250 mg/kg recorded vacuolization, gliosis, blood vessel congestion, hemorrhage, and satellitosis. Conclusion: high oral dosages of isotretinoin influence animal neurobehavioral behavior because of its effect on brain tissue, as evidenced by its effects on serotonin, acetylcholine, and the COMT enzyme.

Keywords

Iranian Journal of Veterinary Medicine

Articles in Press, Accepted Manuscript
Available Online from 09 December 2024

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