Pesticide Biochemistry and Physiology最新文献

Indoxacarb is a chiral insecticide that consists of two enantiomers, S-(+)-indoxacarb and R-(−)-indoxacarb, of which only S-(+)-indoxacarb has insecticidal activity. Previous enantioselective toxicology studies of indoxacarb focused mostly on simple environmental model organisms. The lack of a toxicology evaluation of indoxacarb conducted in a mammalian system could mean that the extent of the potential health risk posed by the insecticide to humans is not adequately known. In this study, we reported on a new pair of enantiomers, S-IN-RM294 and R-IN-RM294, derived from the metabolic breakdown of S-(+)-indoxacarb and R-(−)-indoxacarb, respectively, in rats. The toxicokinetics of S-(+)-indoxacarb, R-(−)-indoxacarb, S-IN-RM294, and R-IN-RM294 in rats were evaluated to provide a more comprehensive risk assessment of these molecules. The bioavailability and excretion rates of both S-(+)-indoxacarb and R-(−)-indoxacarb were relatively low, which may be due to their faster metabolism and accumulation in the tissues. In addition, there were significant differences in the metabolism and distribution between the two indoxacarb enantiomers and their metabolites in vivo. S-(+)-Indoxacarb was found to be more easily metabolized in the blood compared with R-(−)-indoxacarb, as shown by the differences in pharmacokinetic parameters between oral and intravenous administration. Analysis of their tissue distribution showed that S-(+)-indoxacarb was less likely to accumulate in most tissues. The results obtained for the two metabolites were consistent with those of the two parent compounds. S-IN-RM294 was more readily cleared from the blood and less likely to accumulate in the tissues compared with R-IN-RM294. Therefore, whether from the perspective of insecticidal activity or from the perspective of mammalian and environmental friendliness, the application of optically pure S-(+)-indoxacarb in agriculture may be a more efficient and safer strategy.

Acephate and chlorantraniliprole are two insecticides widely used in agricultural applications. Several studies were focused on the mode of action and related biological and cellular level expressions. However, the sub-lethal dose and related molecular expression level of acephate and chlorantraniliprole have not been evaluated or studied to the same degree. In this study, we investigated the sub-lethal toxicity of acephate and chlorantraniliprole in Drosophila melanogaster. The EC₅₀ value was recorded with high difference, and is found to be 1.9 μg/ml and 0.029 μg/ml respectively for acephate and chlorantraniliprole, the difference is simply because of the different modes of action. The 1/5th EC₅₀ concentration was selected for studying the pesticide induced transcriptomics in D. melanogaster. Both pesticides significantly altered the expression profile of several transcripts which are involved in proteolysis, detoxification, chromosome associated proteins and immune response genes and so on. The effect of both pesticides on D. melanogaster was further explored by screening the genes involved in toxicity, which were analyzed using, GO and KEGG pathways. The results revealed that the sub-lethal exposure of both pesticides caused significant changes in the global gene transcription profiles and each pesticide had their unique mode of alteration in the D. melanogaster.

The role of melatonin (MT), an essential phytohormone controlling the physiological and biochemical reactions of plants to biotic and abiotic stress, in alleviating pesticide phytotoxicity remains unclear. This study explores the effects of MT (0 and 200 mg/L) and six doses of fluroxypyr-meptyl (FLUME) (0–0.14 mg/L) on the physiological response of rice (Oryza sativa). FLUME exposure inhibited the growth of rice seedlings, with MT treatment ameliorating this effect. To determine the biochemical processes and catalytic events involved in FLUME breakdown in rice, six rice root and shoot libraries exposed to either FLUME or FLUME–MT were generated and then subjected to RNA-Seq–LC-Q-TOF-HRMS/MS analyses. The results showed that 1510 root genes and 139 shoot genes exhibited higher upregulation in plants treated with an ecologically realistic FLUME concentration and MT than in those treated with FLUME alone. Gene enrichment analysis revealed numerous FLUME-degradative enzymes operating in xenobiotic tolerance to environmental stress and molecular metabolism. Regarding the FLUME degradation process, certain differentially expressed genes were responsible for producing important enzymes, such as cytochrome P450, glycosyltransferases, and acetyltransferases. Four metabolites and ten conjugates in the pathways involving hydrolysis, malonylation, reduction, glycosylation, or acetylation were characterized using LC-Q-TOF-HRMS/MS to support FLUME-degradative metabolism. Overall, external application of MT can increase rice tolerance to FLUME-induced oxidative stress by reducing phytotoxicity and FLUME accumulation. This study provides insights into MT's role in facilitating FLUME degradation, with potential implications for engineering genotypes supporting FLUME degradation in paddy crops.

Emamectin benzoate (EMB), commonly used as an insecticide in fishery production, inevitably leaves residual chemicals in aquatic environments. High-level EMB exposure can cause severe damage to multiple systems of marine animals, potentially through mechanisms involving severe mitochondrial damage and oxidative stress. However, it is not clear yet how EMB exposure at a certain level can cause damage to fish kidney tissue. In this study, we exposed carps to an aquatic environment containing 2.4 μg/L of EMB and cultured carp kidney cells in vitro, established a cell model exposed to EMB. Our findings revealed that EMB exposure resulted in severe kidney tissue damage in carp and compromised the viability of grass carp kidney cells (CIK cells). By RNA-seq analysis, EMB exposure led to significant differences in mitochondrial homeostasis, response to ROS, ferroptosis, and autophagy signals in carp kidney tissue. Mechanistically, EMB exposure induced mitochondrial oxidative stress by promoting the generation of mitochondrial superoxide and reducing the activity of antioxidant enzymes. Additionally, EMB exposure triggered loss of mitochondrial membrane potential, an imbalance in mitochondrial fusion/division homeostasis, and dysfunction in oxidative phosphorylation, ultimately impairing ATP synthesis. Notably, EMB exposure also accelerated excessive autophagy and ferroptosis of cells by contributing to the formation of lipid peroxides and autophagosomes, and the deposition of Fe²⁺. However, N-acetyl-L-cysteine (NAC) treatment alleviated the damage and death of CIK cells by inhibiting oxidative stress. Overall, our study demonstrated that EMB exposure induced mitochondrial oxidative stress, impaired mitochondrial homeostasis, and function, promoted autophagy and ferroptosis of kidney cells, and ultimately led to kidney tissue damage in carp. Our research enhanced the toxicological understanding on EMB exposure and provides a model reference for comparative medicine.

Energy metabolism is essential for insect development, reproduction and detoxification. Insects often reallocate energy and resources to manage external stress, balancing the demands of detoxification and reproduction. Glucose transport 4 (Glut4), a glucose transporter, is involved in glucose and lipid metabolism. However, the specific molecular mechanism of Glut4 in insect reproduction, and its role in the response to insecticide-induced oxidative stress remain unclear. In this study, LmGlut4 was identified and analyzed in Locusta migratoria. Silencing of LmGlut4 significantly reduced vitellogenin (Vg) biosynthesis in the fat body and Vg absorption by oocytes, ultimately hindering ovarian development and oocyte maturation. Knockdown of LmGlut4 also inhibited the biosynthesis of key insect hormones, such as juvenile hormone (JH), 20-hydroxyecdysone (20E) and insulin. Furthermore, LmGlut4 knockdown led to reduced triglyceride (TG) and glycogen content in the fat body and ovary, as well as decreased capacity for trehalose biosynthesis in adipocytes. Additionally, dsLmGlut4-treated locusts showed heightened sensitivity to deltamethrin, leading to increased triglyceride depletion during detoxification. This study sheds light on the biological function of LmGlut4 in the ovary and provides potential target genes for exploring biological pest management strategies.

Tuta absoluta is one of the most destructive and invasive insect pests throughout the world. It feeds on numerous solanaceous plant species and has developed resistance to most types of popular insecticides. Tetraniliprole is a novel diamide chemical agent that acts as a modulator of the ryanodine receptor. To establish T. absoluta susceptibility to tetraniliprole and to understand potential mechanisms of resistance, we monitored 18 field populations of T. absoluta collected from northern China. One field-evolved resistant population, Huailai (HL), showed moderate resistance to tetraniliprole (36.2-fold) in comparison with susceptible strain YN-S. Assays of cross-resistance, synergism, metabolic enzyme activity, and inheritance of resistance were performed with YN-S strain and HL population. The latter displayed 12.2- and 6.7-fold cross-resistance to chlorantraniliprole and flubendiamide, respectively, but little cross-resistance to broflanilide (1.6-fold), spinosad (2.1-fold), metaflumizone (1.5-fold), or indoxacarb (2.8-fold). Genetic analyses revealed that tetraniliprole resistance in HL population was autosomal, incompletely dominant, and polygenic. Piperonyl butoxide was found to significantly increase tetraniliprole toxicity, and enzymatic activities of P450 monooxygenase and glutathione S-transferase were significantly higher in HL than YN-S population. These results enhance our knowledge of the inheritance and mechanism of tetraniliprole resistance, enabling future optimization of resistance management strategies.

Mosquitoes are regularly exposed to adverse effects of insecticides employed in field during vector control campaigns. Its primary goal is to eliminate the vector population; nevertheless, this practise typically ignores the residual impacts and long-term repercussions on the remaining population. Here, the current study analysed how sublethal exposure of insecticides alter the life qualities, genotypic and biochemical characteristics of mosquitoes. The resistance ratio value in Laboratory Resistant (Lab-R) larvae increased 10 times (0.010 mg/l to 0.108 mg/l) compared to Laboratory Susceptible (LabS) larvae. It also revealed that the surviving mosquitoes had 50% reduction in hatchability but had longer larval and pupal periods (15 days and 2 days), respectively. The survival rates decrease in female by 2 days but increase in male by 7 days which is of concern and necessitates additional study. Moreover, major role of monooxygenase was confirmed behind resistance development which was further supported by piperonyl butoxide assay where reduction in Tolerance Ratio (TR₅₀) by 12-fold occurred and gene expression profile also showed high expression level of CYP6P12 gene. In resistant strain, cuticular thickness increased by 1.23 times and alteration at codon 1532 (ATC to TTC) on VGSC gene leads to mutation I1532F. The data gleaned from our work highlights the threat of sublethal insecticides on vector control techniques and offers ample evidence that the larval selection alters adult life qualities, metabolic properties and transgenerational features which contributes to the damage caused by resistance.

As an important class of detoxifying enzymes, glutathione S-transferases (GSTs) are pivotal in decreasing insecticide toxicity to insects. Periplaneta americana GSTd1 (PaGSTd1) has been verified as a key enzyme in detoxifying pyrethroid insecticides, but its detoxification capability against a broader spectrum of insecticides has never been investigated. It is revealed that PaGSTd1 expression showed a rapid and significant increase upon exposure to various insecticides (organophosphates, neonicotinoids, and fipronil). Subsequent in vitro metabolic assays indicated that organophosphates, particularly chlorpyrifos-methyl, can be effectively metabolized by PaGSTd1. Further knockdown of PaGSTd1 via RNA interference significantly heightened the susceptibility of P. americana to chlorpyrifos-methyl, underscoring the enzyme's key role in detoxifying chlorpyrifos-methyl. Additionally, this study confirmed that PaGSTd1 cannot mitigate insecticide toxicity through countering oxidative stress. Collectively, these findings elucidate the involvement of PaGSTd1 in the detoxification processes for organophosphates, offering a comprehensive insight into the metabolic mechanisms mediated by GSTs in P. americana. This research provides a foundational understanding for managing GSTs-mediated metabolic resistance in this species, which is crucial for effective pest control strategies.

The novel bactericidal target—filamentous temperature-sensitive protein Z (FtsZ)—has drawn the attention of pharmacologists to address the emerging issues with drug/pesticide resistance caused by pathogenic bacteria. To enrich the structural diversity of FtsZ inhibitors, the antibacterial activity and structure-activity relationship (SAR) of natural sanguinarine and its analogs were investigated by using natural-products repurposing strategy. Notably, sanguinarine and chelerythrine exerted potent anti-Xanthomonas oryzae pv. oryzae (Xoo) activity, with EC₅₀ values of 0.96 and 0.93 mg L⁻¹, respectively, among these molecules. Furthermore, these two compounds could inhibit the GTPase activity of XooFtsZ, with IC₅₀ values of 241.49 μM and 283.14 μM, respectively. An array of bioassays including transmission electron microscopy (TEM), fluorescence titration, and Fourier transform infrared spectroscopy (FT-IR) co-verified that sanguinarine and chelerythrine were potential XooFtsZ inhibitors that could interfere with the assembly of FtsZ filaments by inhibiting the GTPase hydrolytic ability of XooFtsZ protein. Additionally, the pot experiment suggested that chelerythrine and sanguinarine demonstrated excellent curative activity with values of 59.52% and 54.76%, respectively. Excitedly, these two natural compounds also showed outstanding druggability, validated by acceptable drug-like properties and low toxicity on rice. Overall, the results suggested that chelerythrine was a new and potential XooFtsZ inhibitor to develop new bactericide and provided important guiding values for rational drug design of FtsZ inhibitors. Notably, our findings provide a novel strategy to discover novel, promising and green bacterial compounds for the management of plant bacterial diseases.

To accommodate growth, insects must periodically shed their exoskeletons. In Manduca sexta, Drosophila melanogaster and Tribolium castaneum, Bursicon (Burs)/ Partner of bursicon (Pburs)-LGR2 signal is an indispensable component for the proper execution of ecdysis behavior during adult eclosion. Nevertheless, the behavioral events and the roles of bursicon signaling in other insects deserve further exploration. In the current paper, we found that the pupal-adult ecdysis in Henosepilachna vigintioctomaculata could be divided into three distinct stages, preecdysis, ecdysis and postecdysis. Preecdysis behavioral sequences included abdomen twitches, dorsal-ventral contractions and air filling that function to loosen the old cuticle. Ecdysis events began with anterior-posterior contractions that gradually split the old integument along the dorsal body midline, followed by freeing of legs and mouthparts, and culminated in detachment from pupal cuticle. Postecdysis behavioral processes contained three actions: perch selection and stretching of elytra and hindwings. RNA interference for HvBurs, HvPburs or Hvrk (encoding LGR2) strongly impaired wing expansion actions, and slightly influenced preecdysis and ecdysis behaviors. The RNAi beetles failed to extend their elytra and hindwings. In addition, injected with dsrk also caused kinked femurs and tibia. Our findings establish that bursicon pathway is involved in regulation of adult eclosion behavior, especially wing expansion motor programs. Given that wings facilitate food foraging, courtship, predator avoidance, dispersal and migration, our results provide a potential target for controlling H. vigintioctomaculata.