Pro-apoptotic effects of low doses of dimethoate in rat brain

Area of Science:

• Neuroscience
• Toxicology
• Cell Biology

Background:

• Organophosphate insecticides like dimethoate (DMT) are widely used, raising concerns about potential neurotoxic effects from chronic low-dose exposure via food and water residues.
• Understanding the mechanisms of DMT neurotoxicity is crucial for assessing risks associated with pesticide exposure.

Purpose of the Study:

• To investigate the effects of sub-chronic low-dose dimethoate (DMT) exposure on cell death pathways in the rat brain.
• To examine the impact of DMT on oxidative stress and neuronal integrity in the cortex (Cx) and substantia nigra (SN).

Main Methods:

• Male Wistar rats were administered a low dose of DMT (15 mg/kg b.w.) for 5 weeks.
• Assessed markers of apoptosis, including cytochrome C (CytC) release, Bax/Bcl-2 ratio, and caspase-3 activity in brain regions.
• Evaluated lipid peroxidation and mitochondrial respiratory complex activity.
• Quantified tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra (SN).

Main Results:

• DMT exposure increased CytC release, elevated the Bax/Bcl-2 ratio, and enhanced caspase-3 and calpain activity in both cortex and substantia nigra.
• Oxidative damage to lipids was observed, with an increase in saturated over unsaturated fatty acids.
• No significant effect of DMT on mitochondrial respiratory complex activity was found.
• A decrease in TH-immunoreactive neurons in the SN was observed, comparable to age-related neuronal loss.

Conclusions:

• Sub-chronic low-dose dimethoate exposure activates pro-apoptotic pathways in the rat brain.
• DMT-induced oxidative stress and neuronal loss in the substantia nigra may contribute to neurodegenerative processes.
• These findings suggest a potential etiological role for dimethoate residues in neurodegenerative diseases.