Effects of the carbamates fenoxycarb, propamocarb and propoxur on energy supply, glucose utilization and SH-groups in neurons

Abstract

Carbamates belonged to an older insecticide group, with propoxur being representative of this group. However, today carbamates with hormonal effects on insects, like fenoxycarb, or with fungicide properties, like propamocarb, are also used. The goal was a comparison of three structurally and functional different carbamates with a possibly common toxicological mechanism. Primary neuronal cell cultures of the rat are a well established model to identify neurotoxic compounds like n-hexane or acrylamide. In this cell culture model endpoints such as viability, energy supply, glucose consumption, glutathione (GSH) levels and cytoskeleton elements were determined. Added to cultured rat cortical neurons for 1 week, fenoxycarb, propamocarb and propoxur considerably decreased ATP levels, mitochondrial membrane potential and glucose consumption. Besides this, fenoxycarb and propamocarb had an impact on neurofilaments. After recovery for 1 week, propoxur also showed effects on neurofilaments, whereas with the other carbamates no tendency for a recovery was seen. These effects were prevented completely by pyruvate for propoxur and propamocarb, and partly so for fenoxycarb. In contrast to the main experimental design, GSH was determined after 1-h treatment with the test substances. Surprisingly, the compounds had only slight or no effect on the GSH level within this time. Further mechanistic studies indicated that carbamates primarily interacted with SH-groups, most likely by interfering with glycolysis and the construction of fibrillary proteins like neurofilaments. The prevention by pyruvate and acetylcysteine pointed to these biochemical endpoints.

Metabolism of Pyrethroids by Mosquito Cytochrome P450 Enzymes: Impact on Vector Control

“…This can be accomplished because other than targeting on sodium channels of nervous system, pyrethroids possess toxic effects on cells such as inhibition of cell mitochondrial complex I or causing DNA damage and cell death (Gassner et al, 1997;Patel et al, 2007;Naravaneni & Jamil, 2005). Similar cell death and cytotoxic to cells caused by organophosphates and carbamate insecticides have also been reported (Maran et al, 2010;Schmuck & Mihail, 2004). This is supported by that we previously observed cytotoxic effects of deltamthrin on insect Sf9 cells.…”

Mechanism underlying the effect of long‐term exposure to low dose of pesticides on DNA integrity

“…Likewise, toxic metal compounds inhibited DNA repair processes by binding to sulfhydryls (SH), thus causing protein denaturation and inhibiting enzyme activity . Reaction of carbamates with SH‐groups was clearly shown over a long‐term exposure period, but not after short‐term treatment . Recent reports also showed that redox changes affecting cysteines significantly decreases OGG1's activity .…”

Inhibition of the transforming growth factor-β/SMAD cascade mitigates the anti-neurogenic effects of the carbamate pesticide carbofuran

“…Carbofuran impairs the energy state of neurons by inhibition of glycolysis and decreases ATP levels along with reduced dendritic length and spine density of pyramidal neurons in the hippocampus. It induces DNA fragmentation, resulting in apoptosis and loss of hippocampal neurons (23,25). It has also been reported that low-dose exposure of carbofuran causes changes in lipid composition and membrane-bound enzyme activity and also disturbs synaptosomal calcium homeostasis along with neurophysiological and neurobehavioral alterations in rodents (26 -28).…”