Neuroprotective Role of Coenzyme Q10 against Dysfunction of Mitochondrial Respiratory Chain at Rostral Ventrolateral Medulla during Fatal Mevinphos Intoxication in the Rat

Abstract

We evaluated the functional changes in the mitochondrial respiratory chain at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, in an experimental model of fatal organophosphate poisoning using the insecticide mevinphos (Mev). We also investigated the neuroprotective role of coenzyme Q10 (CoQ10) in this process. Intravenous administration of Mev (1 mg/kg) in Sprague-Dawley rats maintained with propofol elicited an initial hypertension followed by hypotension, accompanied by bradycardia, with death ensuing within 10 min. Enzyme assay revealed a significant depression of the activity of nicotinamide adenine dinucleotide cytochrome c reductase, succinate cytochrome c reductase, and cytochrome c oxidase in the RVLM during this fatal Mev intoxication. ATP production also underwent a significant decrease. Pretreatment by microinjection bilaterally of CoQ10 (4 microg) into the RVLM significantly prevented mortality, antagonized the cardiovascular suppression, and reversed the depressed mitochondrial respiratory enzyme activities, or reduced ATP production in the RVLM induced during Mev intoxication. Our results indicated that dysfunction of mitochondrial respiratory chain and energy production at the RVLM takes place during fatal Mev intoxication. We further demonstrated that CoQ10 provides neuroprotection against Mev-induced cardiovascular depression and fatality through maintenance of activity of the key mitochondrial respiratory enzymes in the RVLM.