Potential role of a newly AChE reactivator in the depressive-like behavior induced by malathion

Anne Suély Pinto Savall1, Eduarda Monteiro Fidelis1, Caroline Brandão Quines1

  • 1Federal University of Pampa - Campus Uruguaiana, Uruguaiana, ZIP code 97500-970, RS, Brazil.

Neuroscience Letters
|February 4, 2021
PubMed

Insights

Organophosphate (OP) exposure, like malathion, can cause depression. The compound (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN) showed antidepressant-like effects and reactivated acetylcholinesterase (AChE) in rats with prolonged malathion exposure.

Area of Science:

  • Neuroscience
  • Toxicology
  • Pharmacology

Background:

  • Organophosphate (OP) compounds, such as malathion, are known to inhibit acetylcholinesterase (AChE), leading to behavioral disorders like depression.
  • The efficacy of current antidotes like atropine-oxime is controversial, necessitating the development of novel therapeutic agents.
  • Previous studies indicated that (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN) possesses AChE reactivating and antidepressant-like properties in acute malathion exposure models.

Purpose of the Study:

  • To investigate the effects of Cℓ-HIN on depressive-like behavior and AChE activity in rats following subchronic exposure to malathion.
  • To evaluate the potential of Cℓ-HIN as a therapeutic agent for prolonged OP intoxication.

Main Methods:

  • Male Wistar rats were co-treated with Cℓ-HIN (5 mg/kg, p.o.) and malathion (1 or 10 mg/kg, i.p.) for 20 days.
  • Depressive-like behavior was assessed using the forced swimming test (FST).
  • AChE activity was measured in the prefrontal cortex and hippocampus.

Main Results:

  • Subchronic exposure to both doses of malathion significantly increased immobility time in the FST, indicating depressive-like behavior.
  • Malathion inhibited AChE activity in the prefrontal cortex but not the hippocampus.
  • Cℓ-HIN treatment attenuated the increased immobility time in rats exposed to the lower dose of malathion (1 mg/kg) and reactivated AChE activity in this group.

Conclusions:

  • Cℓ-HIN demonstrates antidepressant-like effects and AChE reactivating properties in a subchronic malathion exposure model.
  • These findings suggest Cℓ-HIN as a potential therapeutic candidate for managing prolonged organophosphate intoxication.