Acute Paraoxon-Induced Neurotoxicity in a Mouse Survival Model: Oxidative Stress, Dopaminergic System Alterations and Memory Deficits.
Por:
Urquizu E, Paratusic S, Goyenechea J, Gómez-Canela C, Fumàs B, Pubill D, Raldúa D, Camarasa J, Escubedo E and López-Arnau R
Publicada:
14 nov 2024
Ahead of Print:
14 nov 2024
Resumen:
The secondary neurotoxicity induced by severe organophosphorus (OP) poisoning, including paraoxon (POX), is associated with cognitive impairments in survivors, who, despite receiving appropriate emergency treatments, may still experience lasting neurological deficits. Thus, the present study provides a survival mouse model of acute and severe POX poisoning to examine secondary neurotoxicity. Swiss CD-1 male mice were injected with POX (4 mg/kg, s.c.) followed by atropine (4 mg/kg, i.p.), pralidoxime (2-PAM; Pyridine-2-aldoxime methochloride) (25 mg/kg, i.p., twice, 1 h apart) and diazepam (5 mg/kg, i.p.), resulting in a survival rate >90% and Racine score of 5-6. Our results demonstrated that the model showed increased lipid peroxidation, downregulation of antioxidant enzymes and astrogliosis in the mouse hippocampus (HP) and prefrontal cortex (PFC), brain areas involved in cognitive functions. Moreover, dopamine (DA) levels were reduced in the hp, but increased in the PFC. Furthermore, the survival mouse model of acute POX intoxication did not exhibit phenotypic manifestations of depression, anxiety or motor incoordination. However, our results demonstrated long-term recognition memory impairments, which are in accordance with the molecular and neurochemical effects observed. In conclusion, this mouse model can aid in researching POX exposure's effects on memory and developing potential countermeasures against the secondary neurotoxicity induced by severe OP poisoning.
Filiaciones:
:
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
Paratusic S:
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
Goyenechea J:
Department of Analytical Chemistry and Applied (Chromatography Section), School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, 08017 Barcelona, Spain
Gómez-Canela C:
Department of Analytical Chemistry and Applied (Chromatography Section), School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, 08017 Barcelona, Spain
Fumàs B:
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
Pubill D:
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
Raldúa D:
Institute for Environmental Assessment and Water Research (IDAEA-CSIC), 08034 Barcelona, Spain
Camarasa J:
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
Escubedo E:
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
López-Arnau R:
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
Open Access
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