Fipronil metabolism, oxidative sulfone formation and toxicity among organophosphate- and carbamate-resistant and susceptible western corn rootworm populations

Fipronil toxicity and metabolism were studied in two insecticide-resistant, and one susceptible western corn rootworm (Diabrotica virgifera virgifera, LeConte) populations. Toxicity was evaluated by exposure to surface residues and by topical application. Surface residue bioassays indicated no differences in fipronil susceptibility among the three populations. Topical bioassays were used to study the relative toxicity of fipronil, fipronil. the mono-oxygenase inhibitor piperonyl butoxide, and fipronil\u27s oxidative sulfone metabolite in two populations (one resistant with elevated mono-oxygenase activity). Fipronil and fipronil-sulfone exhibited similar toxicity and application of piperonyl butoxide prior to fipronil resulted in marginal effects on toxicity. Metabolism of [14C]fipronil was evaluated in vivo and in vitro in the three rootworm populations. In vivo studies indicated the dominant pathway in all populations to be formation of the oxidative sulfone metabolite. Much lower quantities of polar metabolites were also identified. In vitro studies were performed using sub-cellular protein fractions (microsomal and cytosolic), and glutathione-agarose purified glutathione-Stransferase. Oxidative sulfone formation occurred almost exclusively in in vitro microsomal reactions and was increased in the resistant populations. Highly polar metabolites were formed exclusively in in vitro cytosolic reactions. In vitro reactions performed with purified, cytosolic glutathione-Stransferase (MW=27kDa) did not result in sulfone formation, although three additional polar metabolites not initially detectable in crude cytosolic reactions were detected. Metabolism results indicate both cytochromes P450 and glutathione-S-transferases are important to fipronil metabolism in the western corn rootworm and that toxic sulfone formation by P450 does not affect net toxicity

Fipronil metabolism, oxidative sulfone formation and toxicity among organophosphate- and carbamate-resistant and susceptible western corn rootworm populations

Fipronil toxicity and metabolism were studied in two insecticide-resistant, and one susceptible western corn rootworm (Diabrotica virgifera virgifera, LeConte) populations. Toxicity was evaluated by exposure to surface residues and by topical application. Surface residue bioassays indicated no differences in fipronil susceptibility among the three populations. Topical bioassays were used to study the relative toxicity of fipronil, fipronil. the mono-oxygenase inhibitor piperonyl butoxide, and fipronil\u27s oxidative sulfone metabolite in two populations (one resistant with elevated mono-oxygenase activity). Fipronil and fipronil-sulfone exhibited similar toxicity and application of piperonyl butoxide prior to fipronil resulted in marginal effects on toxicity. Metabolism of [14C]fipronil was evaluated in vivo and in vitro in the three rootworm populations. In vivo studies indicated the dominant pathway in all populations to be formation of the oxidative sulfone metabolite. Much lower quantities of polar metabolites were also identified. In vitro studies were performed using sub-cellular protein fractions (microsomal and cytosolic), and glutathione-agarose purified glutathione-Stransferase. Oxidative sulfone formation occurred almost exclusively in in vitro microsomal reactions and was increased in the resistant populations. Highly polar metabolites were formed exclusively in in vitro cytosolic reactions. In vitro reactions performed with purified, cytosolic glutathione-Stransferase (MW=27kDa) did not result in sulfone formation, although three additional polar metabolites not initially detectable in crude cytosolic reactions were detected. Metabolism results indicate both cytochromes P450 and glutathione-S-transferases are important to fipronil metabolism in the western corn rootworm and that toxic sulfone formation by P450 does not affect net toxicity

Ameliorative and protective effects of prebiotic, microbial levan in common carp, (Cyprinus carpio) fry under experimental exposure to fipronil

This study investigated the immuno-toxicological effect of the insecticide fipronil at sublethal concentration (10% of LC50) and the potential ameliorative effects of dietary microbial levan in Cyprinus carpio fry. Fish were randomly distributed into five treatments in triplicate for 60 days. Five different treatment groups were: levan control L0F0 (basal feed + 0% levan without exposure to fipronil), pesticide control L0F (basal feed + 0% levan with exposure to fipronil), other three dietary supplemented groups exposed to fipronil with different inclusion levels of levan at 0.25% (L0.25F), 0.50% (L0.50F) and 0.75% (L0.75F), respectively. The results revealed that feeding common carp with 0.75% dietary levan significantly reduced (P<0.05) glutathione-S-transferase and glutathione peroxidase levels in various tissues. Lipid peroxidation and heat shock protein level was significantly (P<0.05) reduced with supplementation of levan at 0.75% compared to other groups. Higher glycogen content was observed in high levan fed groups. Although fipronil exposure had no signficiant effect on lipid profile levels, dietary levan supplementation decreased lipid profile level in the fish exposed to fipronil stress. Total immunoglobulin and myeloperoxidase content of common carp showed an increasing trend with the concomitant increase in the level of levan administration in the diet. Overall, results revlealed that microbial levan at 0.75% in the fipronil induced C. carpio fry mitigated the stress due to its potent nutraceutical properties, thus presenting a promising immuno-additive for aquaculture

Toxicity interaction of fipronil and imidacloprid against Coptotermes formasanus

The Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), is considered one of the most destructive structural pests in the world, especially in warm and humid areas. Insecticide application is an effective strategy in termite control. In recent years, non-repellent insecticides have become popular for their high efficacy due to delayed toxicity and horizontal transfer. Fipronil (registered name Termidor®) and imidacloprid (registered name Premise®) have been applied to the perimeter of millions of houses in the United States. Fipronil and imidacloprid have different modes of action which may produce a synergistic effect when combined. There have been no studies on the toxicity interaction of fipronil and imidacloprid against termites including the Formosan subterranean termite. The original objective of the research was to determine whether combinations of the termiticides lead to enhanced toxicity against Formosan subterranean termites. Combinations of the non-repellent insecticides were treated on filter paper and sand for evaluation. After timed exposures, any living termites were transferred to untreated Petri dishes. Mortality of termites was recorded before and after the transfer. Lower mortality was observed when imidacloprid was mixed with fipronil compared to fipronil alone. Mortality was increased by the mixture over imidacloprid alone. To validate these results, more combinations were introduced in the second and third set of experiments. Besides the recording of mortality, the number of excavation holes made by termites in sand was also counted to determine whether excavation activity was related to mortality effects. A second objective was to seek a threshold level whereby the efficacy of fipronil becomes negatively impacted by imidacloprid presence. A threshold of between 15 and 25 ppm imidacloprid added to 100 ppm fipronil reduced the efficacy of fipronil. An increase in the number of excavation holes was significantly associated with a rising mortality, indicating imidacloprid affected the uptake of fipronil by reducing termite excavation behavior of treated soil. In practical terms and of potential concern for homeowners, the studies suggest that the efficacy of Termidor® applied around the perimeters of houses may be negatively affected by the presence of Premise®

Fipronil Promotes Adipogenesis via AMPKα-mediated Pathway in 3T3-L1 Adipocytes

Emerging evidence suggests that organochlorine, organophosphorus and neonicotinoid insecticide exposure may be linked to the development of obesity and type 2 diabetes. However, there is no knowledge of the potential influence of fipronil, which belongs to the phenylpyrazole chemical family, on obesity. Thus, the goal of this study was to determine the role of fipronil in adipogenesis using 3T3-L1 adipocytes. Fipronil treatment, at 10 mM, increased fat accumulation in 3T3-L1 adipocytes as well as promoted key regulators of adipocyte differentiation (CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor gamma-γ), and key regulators of lipogenesis (acetyl-CoA carboxylase and fatty acid synthase). The activation of AMPKα with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) abolished effects of fipronil on increased adipogenesis. These results suggest that fipronil alters adipogenesis and results in increased lipid accumulation through a AMPKα-mediated pathway