Neurotoxicity of Isotretinoin in Mice: Behavioral and Tissue Neurological Function Assessment
نویسندگان
1 Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq.
2 Department of Anesthesia, Medical Technical Institute, Northern Technical University, Mosul, Iraq.
3 Department of Anesthesia, Medical Technical Institute, Northern Technical University, Mosul, Iraq.
doi
10.32598/ijvm.19.4.1005588چکیده
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.Objectives: To evaluate isotretinoin’s effects on the brain and neurotransmitters, as well as its impact on neurobehavior and motor activity. Methods: Fifteen mice were divided into three groups: the first group was a control group, the second group received 125 mg/kg isotretinoin, and the third group received 250 mg/kg orally. Results: The LD50 for isotretinoin is 4841.2 mg/kg. Neurobehavioral measurements of mice revealed 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) significantly altered serotonin levels. Mice treated with 125 mg/kg isotretinoin exhibited a decrease in serotonin levels compared to the control group. Both doses of isotretinoin resulted in significant changes in acetylcholine levels. Isotretinoin (125 mg/kg) slightly increased in acetylcholine levels. The data indicated a significant increase in catechol-O-methyltransferase (COMT) enzyme levels. A histopathological study of the brain revealed that 125 mg/kg isotritinoin induced mild vacuolization, blood vessel congestion, and mild perivascular edema. A high dose (250 mg/kg) resulted in vacuolization, gliosis, blood vessel congestion, hemorrhage and satellitosis. Conclusion: High oral doses of isotretinoin influence animal neurobehavioral behavior due to its effect on brain tissue, as evidenced by its effects on serotonin, acetylcholine and the COMT enzyme.