Dimethyl Disulfide Exerts Insecticidal Neurotoxicity Through Mitochondrial Dysfunction and Activation of Insect K_ATPChannels

Abstract

The plant-derived insecticides have introduced a new concept in insecticide research. In response to insect attacks, some plants can release volatile sulfur compounds such as dimethyl disulfide (DMDS) in the atmosphere, which are lethal for the generalist insects. We demonstrate that DMDS induced an uncommon complex neurotoxic activity. The studies of in vivo toxicity of DMDS in three insect species and mice indicated a highest bioactivity for insects. Although DMDS did not alter the electrophysiological properties of the cockroach Periplaneta americana giant axon, it affected the synaptic transmission at the presynaptic level resulting in an inhibition of the neurotransmitter release. Whole cell patch-clamp experiments performed on cockroach cultured dorsal unpaired median (DUM) neurons revealed a dose-dependent hyperpolarization induced by DMDS associated with a decrease in the input resistance and the disappearance of action potentials. The hyperpolarization was inhibited by glibenclamide and tolbutamide, and was dependent on intracellular ATP concentration, demonstrating a neurotoxicity via the activation of KATP channels. Finally, the same effects observed with oligomycin, 2,4-dinitrophenol, and KCN together with the studies of DMDS toxicity on isolated mitochondria confirmed an unusual action occurring through an inhibition of the mitochondrial respiratory chain complex IV (cytochrome oxydase). This DMDS-induced inhibition of complex IV subsequently decreased the intracellular ATP concentration, which thereby activated neuronal KATP channels mediating membrane hyperpolarization and reduction of neuronal activity.

HIV-1 Transactivator of Transcription Protein Induces Mitochondrial Hyperpolarization and Synaptic Stress Leading to Apoptosis

“…For example, tolbutamide reduces glucose availability to the glycolytic pathway, which in turn reduces the supply of pyruvate to the Kreb's cycle, resulting in decreased production of reduced NADH, and consequent decline in ⌬ m . Notably, one other report has demonstrated a neurotoxic effect that is induced via activation of neuronal KATP channels, and can be blocked by tolbutamide (52), which may be consistent with results shown in this work. Tat may also contribute to increased ⌬ m by other means, including inhibition of the mitochondrial F 1 F 0 -ATP-ase, or increasing electrochemical potential through increased production of (NADH) substrate.…”

Intercropping of lettuce and onion controls caterpillar thread, Agrotis ípsilon major insect pest of lettuce

“…We believe that the border intercropping pattern was the best intercropping pattern of onion with lettuce because, first the caterpillar to enter in the field finds a barrier of onion crop and this attacks the onion, it begins to release a number of volatile organic compounds containing sulfur and these may have a defensive role. This hypothesis is congruent with Huang et al [22], Dugravot et al [23], Rouseff et al [24] and Auger et al [25], who have investigated the role of volatiles compounds released by Allium spp after damaged and those were classified as toxic or repellents for various insect pest. Mann et al [10], observed that Sulfur volatiles from Allium spp.…”

Increased Sulfur Precursors and Volatiles Production by the Leek Allium porrum in Response to Specialist Insect Attack

“…Tests in confined spaces have demonstrated that these products are highly toxic for various species (Auger and Thibout, 2002). One, dimethyl disulfide, interferes with the cytochrome oxidase mitochondrial complex involved in the production of ATP, thus causing a loss of neuronal activity and death in some species (Dugravot et al, 2003). Moreover, tests in natural settings on crucifers (Chew, 1988) have shown that sulfur compounds can act as chemical repellents against herbivores (Auger et al, 1989).…”