Ametryn and Clomazone Disrupt Mitochondrial Bioenergetics in Rat Liver: Evidence for Inhibition of Complexes I and II and ATP Synthase.

Abstract

Ametryn (AMT) and clomazone (CLZ) are commonly used herbicides frequently detected in food and water, raising concerns about potential health risks. This study investigated whether AMT and CLZ impair mitochondrial bioenergetics, a key mechanism linked to hepatotoxicity. Mitochondria were isolated from rat liver and incubated with AMT or CLZ (50-200 µM) to assess respiration, membrane potential (Δψ), ATP production, and the activities of respiratory chain complexes and ATP synthase. Both herbicides significantly inhibited state 3 (ADP-stimulated) respiration with glutamate plus malate, without altering state 4 (basal) respiration. Concentrations above 100 µM reduced Δψ and ATP synthesis in glutamate plus malate or succinate-energized mitochondria. Enzymatic assays revealed inhibition of complex I by both herbicides, complex II by CLZ, and ATP synthase by both. These results highlight mitochondrial oxidative phosphorylation disruption by AMT and CLZ; however, further in situ and in vivo studies are necessary to fully understand their hepatotoxic potential.