The formamidine pesticides chlordimeform and amitraz decrease hepatic glutathione in mice through an interaction with...

Area of Science:

• Toxicology
• Pharmacology
• Biochemistry

Background:

• Formamidine pesticides (chlordimeform, amitraz) may exert toxic effects via alpha 2-adrenoceptors.
• Epinephrine and clonidine decrease hepatic glutathione (GSH) by activating alpha 2-adrenoceptors.
• Alpha 2-antagonists can mitigate GSH depletion and hepatotoxicity from other agents.

Purpose of the Study:

• Investigate if formamidines affect hepatic GSH levels in mice.
• Determine the mechanism of action for formamidine-induced GSH depletion.
• Clarify the role of alpha-adrenoceptors in formamidine toxicity.

Main Methods:

• Administered chlordimeform (CDM) and amitraz (AMZ) to mice in a dose-dependent manner.
• Measured hepatic nonprotein sulfhydryls (NPSH) as an indicator of GSH levels.
• Utilized alpha 2-antagonist (yohimbine), alpha 1-antagonist (prazosin), and beta-antagonist (propranolol) to assess receptor involvement.
• Administered the alpha 2-agonist clonidine and compared its effects.

Main Results:

• Both CDM and AMZ dose-dependently decreased hepatic NPSH by up to 40%.
• The alpha 2-antagonist yohimbine, but not prazosin or propranolol, antagonized the NPSH decrease caused by CDM and AMZ.
• The alpha 2-agonist clonidine also decreased hepatic NPSH, with effects not being additive with formamidines.

Conclusions:

• Formamidine pesticides decrease hepatic GSH levels in mice.
• This effect appears to be mediated through direct interaction with hepatic alpha 2-adrenoceptors.
• The mechanism involves alpha 2-adrenoceptor activation, similar to clonidine.