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Antidepressant-like effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one in rats exposed to malathion: Involvement of BDNF-Trkβ pathway and AChE.
Life Sci. 2020 Jun 02; 256:117892.LS

Abstract

BACKGROUND

Organophosphorus pesticides exert their toxic effects mainly by the inhibition of acetylcholinesterase (AChE), which is related to emotional disorders, such as depression. Atropine-oximes therapy is commonly used; however, the efficacy of oximes in the reactivation of AChE has been inconsistent. The objective of this study was to investigate the possible neuroprotective effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that combines the isatin and oxime functional groups, in rats exposed to malathion. The effect of Cℓ-HIN on the AChE activity and the BDNF-Trkβ pathway in the prefrontal cortex of malathion-exposed rats were tested.

METHODS

Wistar male rats were co-treated with Cℓ-HIN [50 mg/kg (p.o.) (3 mL/kg)] and/or malathion [250 mg/kg (i.p.) (5 mL/kg)] and performed behavioral tests twelve hours after these exposures.

RESULTS

The Cℓ-HIN reversed the increased immobility time in the forced swimming test and the decreased grooming time in the splash test induced by malathion, but any significant difference was observed in locomotion analysis. These results demonstrate the antidepressant-like effect of Cℓ-HIN. The cortical AChE activity was reactivated by Cℓ-HIN in rats exposed to malathion. Malathion induced an increase in Trkβ and a decrease in BDNF levels in the prefrontal cortex of rats, which were avoided by Cℓ-HIN.

CONCLUSION

These findings support the hypothesis that Cℓ-HIN is an AChE reactivator with antidepressant-like properties, which is related to the improvement of BDNF-Trkβ signaling after acute exposure to malathion in rats. Thus, the results allow suggesting the potential use of Cℓ-HIN as an oxime-based therapy against the neurotoxic effects of malathion.

Authors+Show Affiliations

Federal University of Pampa - Campus Uruguaiana, Uruguaiana 97500-970, RS, Brazil.Federal University of Pampa - Campus Uruguaiana, Uruguaiana 97500-970, RS, Brazil.Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil.Federal University of Rio Grande - Campus Carreiros, Rio Grande 96201-900, RS, Brazil.Federal University of Rio Grande - Campus Carreiros, Rio Grande 96201-900, RS, Brazil.Federal University of Pampa - Campus Uruguaiana, Uruguaiana 97500-970, RS, Brazil.Federal University of Pampa - Campus Uruguaiana, Uruguaiana 97500-970, RS, Brazil.Federal University of Pampa - Campus Uruguaiana, Uruguaiana 97500-970, RS, Brazil.Federal University of Pampa - Campus Uruguaiana, Uruguaiana 97500-970, RS, Brazil.Federal University of Pampa - Campus Uruguaiana, Uruguaiana 97500-970, RS, Brazil. Electronic address: simonepinton@unipampa.edu.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32502538

Citation

Savall, Anne Suély Pinto, et al. "Antidepressant-like Effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one in Rats Exposed to Malathion: Involvement of BDNF-Trkβ Pathway and AChE." Life Sciences, vol. 256, 2020, p. 117892.
Savall ASP, Fidelis EM, Angonesi V, et al. Antidepressant-like effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one in rats exposed to malathion: Involvement of BDNF-Trkβ pathway and AChE. Life Sci. 2020;256:117892.
Savall, A. S. P., Fidelis, E. M., Angonesi, V., Bresolin, L., Gervini, V. C., Quines, C., Puntel, R. L., Roos, D. H., de Ávila, D. S., & Pinton, S. (2020). Antidepressant-like effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one in rats exposed to malathion: Involvement of BDNF-Trkβ pathway and AChE. Life Sciences, 256, 117892. https://doi.org/10.1016/j.lfs.2020.117892
Savall ASP, et al. Antidepressant-like Effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one in Rats Exposed to Malathion: Involvement of BDNF-Trkβ Pathway and AChE. Life Sci. 2020 Jun 2;256:117892. PubMed PMID: 32502538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant-like effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one in rats exposed to malathion: Involvement of BDNF-Trkβ pathway and AChE. AU - Savall,Anne Suély Pinto, AU - Fidelis,Eduarda Monteiro, AU - Angonesi,Vanessa, AU - Bresolin,Leandro, AU - Gervini,Vanessa Carratú, AU - Quines,Caroline, AU - Puntel,Robson Luiz, AU - Roos,Daniel Henrique, AU - de Ávila,Daiana Silva, AU - Pinton,Simone, Y1 - 2020/06/02/ PY - 2020/04/28/received PY - 2020/05/29/revised PY - 2020/05/30/accepted PY - 2020/6/6/pubmed PY - 2020/6/6/medline PY - 2020/6/6/entrez KW - Acetylcholinesterase KW - Isatin KW - Neurotrophic factor KW - Organophosphate KW - Oxime SP - 117892 EP - 117892 JF - Life sciences JO - Life Sci. VL - 256 N2 - BACKGROUND: Organophosphorus pesticides exert their toxic effects mainly by the inhibition of acetylcholinesterase (AChE), which is related to emotional disorders, such as depression. Atropine-oximes therapy is commonly used; however, the efficacy of oximes in the reactivation of AChE has been inconsistent. The objective of this study was to investigate the possible neuroprotective effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that combines the isatin and oxime functional groups, in rats exposed to malathion. The effect of Cℓ-HIN on the AChE activity and the BDNF-Trkβ pathway in the prefrontal cortex of malathion-exposed rats were tested. METHODS: Wistar male rats were co-treated with Cℓ-HIN [50 mg/kg (p.o.) (3 mL/kg)] and/or malathion [250 mg/kg (i.p.) (5 mL/kg)] and performed behavioral tests twelve hours after these exposures. RESULTS: The Cℓ-HIN reversed the increased immobility time in the forced swimming test and the decreased grooming time in the splash test induced by malathion, but any significant difference was observed in locomotion analysis. These results demonstrate the antidepressant-like effect of Cℓ-HIN. The cortical AChE activity was reactivated by Cℓ-HIN in rats exposed to malathion. Malathion induced an increase in Trkβ and a decrease in BDNF levels in the prefrontal cortex of rats, which were avoided by Cℓ-HIN. CONCLUSION: These findings support the hypothesis that Cℓ-HIN is an AChE reactivator with antidepressant-like properties, which is related to the improvement of BDNF-Trkβ signaling after acute exposure to malathion in rats. Thus, the results allow suggesting the potential use of Cℓ-HIN as an oxime-based therapy against the neurotoxic effects of malathion. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/32502538/Antidepressant-like_effect_of_(3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one_in_rats_exposed_to_malathion:_Involvement_of_BDNF-Trkβ_pathway_and_AChE L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(20)30642-1 DB - PRIME DP - Unbound Medicine ER -
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