Acute oral toxicity, apoptosis, and immune response in nurse bees (Apis mellifera) induced by flupyradifurone

The potential toxicity of flupyradifurone (FPF) to honey bees has been a subject of controversy in recent years. Understanding the effect of pesticides on nurse bees is important because the fitness of nurse bees is critical for in-hive activities, such as larval survival and performing hive maintenance. In order to evaluate the acute oral toxicity of flupyradifurone on nurse bees, flupyradifurone at five different concentrations was selected to feed both larvae and nurse bees. Our results showed that nurse bees were more sensitive to flupyradifurone than larvae (LD50 of the acute oral toxicity of flupyradifurone was 17.72 μg a.i./larva and 3.368 μg a.i./nurse bee). In addition, the apoptotic rates of neurons in mushroom bodies of nurse bees were significantly induced by flupyradifurone at sublethal concentrations (8 mg/L, 20 mg/L, and 50 mg/L) and the median lethal concentration LC50 (125 mg/L). The expression of immune-related genes (Hsp90, Toll-8/Tollo, and defensin) was significantly changed in exposed nurse bees at the field-realistic concentration of flupyradifurone. However, three detoxifying enzyme genes (CYP9Q1, -2, and -3) were not affected by pesticide exposure. Our data suggest that although flupyradifurone had a relatively lower acute oral toxicity than many other common pesticides, exposures to the field-realistic and other sublethal concentrations of flupyradifurone still have cytotoxicity and immune-responsive effects on nurse bees. Therefore, flupyradifurone should be considered for its application in crops.

[1]  K. Chon,et al.  Assessment of acute and chronic toxicity of cyantraniliprole and sulfoxaflor on honey bee (Apis mellifera) larvae. , 2022, Pest Management Science.

[2]  M. Steinert,et al.  What about honey bee jelly? Pesticide residues in larval food jelly of the Western honey bee Apis mellifera. , 2022, The Science of the total environment.

[3]  Gyan P. Harwood,et al.  Butenolide Insecticide Flupyradifurone Affects Honey Bee Worker Antiviral Immunity and Survival , 2022, Frontiers in Insect Science.

[4]  L. Foster,et al.  Drone honey bees are disproportionately sensitive to abiotic stressors despite expressing high levels of stress response proteins , 2022, Communications Biology.

[5]  Priyadarshini Chakrabarti,et al.  Honey Bee (Hymenoptera: Apidae) Nursing Responses to Cuticular Cues Emanating from Short-term Changes in Larval Rearing Environment , 2021, Journal of insect science.

[6]  N. Adgaba,et al.  Current knowledge about behaviors of honey bee queens with highlighting of the importance future studies , 2021, The Journal of Basic and Applied Zoology.

[7]  Edward L. Evans,et al.  New Extensibility and Scripting Tools in the ImageJ Ecosystem , 2021, Current protocols.

[8]  David T. W. Tzeng,et al.  Missing Nurse Bees—Early Transcriptomic Switch From Nurse Bee to Forager Induced by Sublethal Imidacloprid , 2021, Frontiers in Genetics.

[9]  Jing Gao,et al.  The Effects of Exposure to Flupyradifurone on Survival, Development, and Foraging Activity of Honey Bees (Apis mellifera L.) under Field Conditions , 2021, Insects.

[10]  Li Cao,et al.  Immune Response and Hemolymph Microbiota of Apis mellifera and Apis cerana After the Challenge With Recombinant Varroa Toxic Protein , 2020, Journal of Economic Entomology.

[11]  Yahya Al Naggar,et al.  The novel insecticides flupyradifurone and sulfoxaflor do not act synergistically with viral pathogens in reducing honey bee (Apis mellifera) survival but sulfoxaflor modulates host immunocompetence , 2020, Microbial biotechnology.

[12]  Yanchun Deng,et al.  Screening and Validation of Reference Genes for RT-qPCR Under Different Honey Bee Viral Infections and dsRNA Treatment , 2020, Frontiers in Microbiology.

[13]  A. Melathopoulos,et al.  Field rates of Sivanto™ (flupyradifurone) and Transform® (sulfoxaflor) increase oxidative stress and induce apoptosis in honey bees (Apis mellifera L.) , 2020, PloS one.

[14]  Jing Gao,et al.  Acute and chronic toxicity of acetamiprid, carbaryl, cypermethrin and deltamethrin to Apis mellifera larvae reared in vitro. , 2020, Pest management science.

[15]  J. Nieh,et al.  Lethal and sublethal synergistic effects of a new systemic pesticide, flupyradifurone (Sivanto®), on honeybees , 2019, Proceedings of the Royal Society B.

[16]  O. Malaspina,et al.  Exposure to thiamethoxam during the larval phase affects synapsin levels in the brain of the honey bee. , 2019, Ecotoxicology and environmental safety.

[17]  Z. Simões,et al.  Silencing of Apis mellifera dorsal genes reveals their role in expression of the antimicrobial peptide defensin‐1 , 2018, Insect molecular biology.

[18]  Yu Cheng Zhu,et al.  Responses of Honey Bees to Lethal and Sublethal Doses of Formulated Clothianidin Alone and Mixtures , 2018, Journal of Economic Entomology.

[19]  J. Tu,et al.  HSP90 promotes cell glycolysis, proliferation and inhibits apoptosis by regulating PKM2 abundance via Thr-328 phosphorylation in hepatocellular carcinoma , 2017, Molecular Cancer.

[20]  J. Nieh,et al.  The pesticide flupyradifurone impairs olfactory learning in Asian honey bees (Apis cerana) exposed as larvae or as adults , 2017, Scientific Reports.

[21]  C. Jack,et al.  Acute toxicity of five pesticides to Apis mellifera larvae reared in vitro. , 2017, Pest management science.

[22]  J. Snow,et al.  The heat shock response and humoral immune response are mutually antagonistic in honey bees , 2017, Scientific Reports.

[23]  L. Stelinski,et al.  Behavioral and hormetic effects of the butenolide insecticide, flupyradifurone, on Asian citrus psyllid, Diaphorina citri , 2017 .

[24]  I. Wojda Temperature stress and insect immunity. , 2017, Journal of thermal biology.

[25]  R. Moritz,et al.  Thiacloprid alters social interactions among honey bee workers (Apis mellifera) , 2017 .

[26]  P. Javorskỳ,et al.  Formetanate toxicity and changes in antioxidant enzyme system of Apis mellifera larvae , 2017, Environmental Science and Pollution Research.

[27]  L. Chittka,et al.  A Simple Computational Model of the Bee Mushroom Body Can Explain Seemingly Complex Forms of Olfactory Learning and Memory , 2017, Current Biology.

[28]  J. Ellis,et al.  Protocol for the in vitro rearing of honey bee (Apis mellifera L.) workers , 2016 .

[29]  O. Malaspina,et al.  In vitro effects of thiamethoxam on larvae of Africanized honey bee Apis mellifera (Hymenoptera: Apidae). , 2015, Chemosphere.

[30]  Yanyan Wu,et al.  Programmed Cell Death in the Honey Bee (Apis mellifera) (Hymenoptera: Apidae) Worker Brain Induced by Imidacloprid , 2015, Journal of economic entomology.

[31]  C. Pirk,et al.  Detoxification mechanisms of honey bees (Apis mellifera) resulting in tolerance of dietary nicotine , 2015, Scientific Reports.

[32]  M. E. Beck,et al.  Flupyradifurone: a brief profile of a new butenolide insecticide , 2014, Pest management science.

[33]  Xinyang Hu,et al.  Hypoxia Preconditioned Mesenchymal Stem Cells Prevent Cardiac Fibroblast Activation and Collagen Production via Leptin , 2014, PloS one.

[34]  Geraldine A. Wright,et al.  Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees , 2013, Nature Communications.

[35]  Daniela Laurino,et al.  Toxicity of neonicotinoid insecticides on different honey bee genotypes , 2013 .

[36]  E. Yang,et al.  Impaired Olfactory Associative Behavior of Honeybee Workers Due to Contamination of Imidacloprid in the Larval Stage , 2012, PloS one.

[37]  J. Brunet,et al.  Neural effects of insecticides in the honey bee , 2012, Apidologie.

[38]  T. Blacquière,et al.  Neonicotinoids in bees: a review on concentrations, side-effects and risk assessment , 2012, Ecotoxicology.

[39]  B. Charroux,et al.  Toll-8/Tollo Negatively Regulates Antimicrobial Response in the Drosophila Respiratory Epithelium , 2011, PLoS pathogens.

[40]  M. Berenbaum,et al.  CYP9Q-mediated detoxification of acaricides in the honey bee (Apis mellifera) , 2011, Proceedings of the National Academy of Sciences.

[41]  J. Dupuis,et al.  Expression patterns of nicotinic subunits α2, α7, α8, and β1 affect the kinetics and pharmacology of ACh-induced currents in adult bee olfactory neuropiles. , 2011, Journal of neurophysiology.

[42]  J. Evans Beepath: an ordered quantitative-PCR array for exploring honey bee immunity and disease. , 2006, Journal of invertebrate pathology.

[43]  Draft OECD Guideline for the Testing of Chemicals , 2006 .

[44]  S. Farris Evolution of insect mushroom bodies: old clues, new insights , 2005 .

[45]  A. Sabatini,et al.  Effects of imidacloprid administered in sub-lethal doses on honey bee behaviour. Laboratory tests , 2003 .

[46]  P. Déglise,et al.  The insecticide imidacloprid is a partial agonist of the nicotinic receptor of honeybee Kenyon cells , 2002, Neuroscience Letters.

[47]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[48]  A. Stork,et al.  Risk posed to honeybees (Apis mellifera L, Hymenoptera) by an imidacloprid seed dressing of sunflowers. , 2001, Pest management science.

[49]  L. Belzunces,et al.  Characteristics of imidacloprid toxicity in two Apis mellifera subspecies , 2000 .

[50]  G. Robinson,et al.  Larval and pupal development of the mushroom bodies in the honey bee, Apis mellifera , 1999, The Journal of comparative neurology.

[51]  R. Menzel,et al.  Nicotinic acetylcholine currents of cultured Kenyon cells from the mushroom bodies of the honey bee Apis mellifera , 1999, The Journal of physiology.

[52]  G. Bicker,et al.  Calcium imaging reveals nicotinic acetylcholine receptors on cultured mushroom body neurons. , 1994, Journal of neurophysiology.

[53]  J. Lewis,et al.  Probit Analysis (3rd ed). , 1972 .

[54]  M. Lindauer,et al.  Division of Labour in the Honeybee Colony , 1953 .