Elucidation and active ingredient identification of aqueous extract of Ficus exasperata Vahl leaf against bisphenol A-induced toxicity through in vivo and in silico assessments.

Bisphenol A (BPA), an endocrine-disrupting chemical, poses significant health problems due to its induction of oxidative stress, inflammation, etc. Whereas Ficus exasperata Vahl leaf (FEVL) was reported for its ethnopharmacological properties against several ailments owing to its antioxidant, anti-inflammatory properties, etc. Here, we aim to elucidate and identify the bioactive compounds of aqueous extract of FEVL (AEFEVL) against BPA-induced toxicity using in vivo and in silico assessments. To determine the BPA toxicity mechanism and safe doses of AEFEVL, graded doses of BPA (0-400 µM) and AEFEVL (0-2.0 mg/10 g diets) were separately fed to flies to evaluate survival rates and specific biochemical markers. The mitigating effect of AEFEVL (0.5 and 1.0 mg/10 g diet) against BPA (100 and 200 µM)-induced toxicity in the flies after 7-day exposure was also carried out. Additionally, molecular docking analysis of BPA and BPA-o-quinone (BPAQ) against selected antioxidant targets, and HPLC-MS-revealed AEFEVL compounds against Keap-1 and IKKß targets, followed by ADMET analysis, was conducted. Emergence rate, climbing ability, acetylcholinesterase, monoamine oxidase-B, and glutathione-S-transferase activities, and levels of total thiols, non-protein thiols, nitric oxide, protein carbonyl, malondialdehyde, and cell viability were evaluated. BPA-induced altered biochemical and behavioral parameters were significantly mitigated by AEFEVL in the flies (p < 0.05). BPAQ followed by BPA exhibited higher inhibitory activity, and epigallocatechin (EGC) showed the highest inhibitory activity among the AEFEVL compounds with desirable ADMET properties. Conclusively, our findings revealed that EGC might be responsible for the mitigative effect displayed by AEFEVL in BPA-induced toxicity in D. melanogaster.

Mitochondrial dysfunction and NDUFS3: Insights from a PINK1B9 Drosophila model in Parkinson's disease pathogenesis.

PTEN-induced kinase1 (PINK1) mutation is the main cause of autosomal recessive inheritance and early-onset Parkinson's disease. Mitochondrial respiratory chain complex I (CI) functional impairment has been considered to be an important factor in the pathogenesis of PD in recent years. In addition, NDUFS3 (nicotinamide adenine dinucleotide deoxylase iron-thionein 3) is one of the core subunits of mitochondrial CI. Therefore, this study explored the role of NDUFS3 gene in PINK1B9 transgenic Drosophila and its possible related mechanisms. In this study, the PD transgenic Drosophila model of MHC-Gal4/UAS system was selected to specifically activate the expression of PINK1B9 gene in the chest muscle tissue of Drosophila melanogaster. NDUFS3 RNAi interference was used to interfere with PINK1B9 transgenic Drosophila melanogaster and its effect on PD transgenic flies was studied. The results suggest that down-regulation of NDUFS3 gene expression may have a protective effect on PINK1B9 transgenic Drosophila melanogaster, and we speculate that down-regulation of NDUFS3 gene expression to reduce oxidative stress and restore mitochondrial function may be related to mitochondrial stress response.

Mechanisms for controlling Dorsal nuclear levels.

Formation of the Dorsal nuclear-cytoplasmic gradient is important for the proper establishment of gene expression patterns along the dorsal-ventral (DV) axis during embryogenesis in Drosophila melanogaster. Correct patterning of the DV axis leads to formation of the presumptive mesoderm, neurogenic ectoderm, dorsal ectoderm, and amnioserosa, which are tissues necessary for embryo viability. While Toll signaling is necessary for Dorsal gradient formation, a gradient still forms in the absence of Toll, suggesting there are additional mechanisms required to achieve correct nuclear Dorsal levels. Potential mechanisms include post-translational modification, shuttling, and nuclear spacing. Post-translational modification could affect import and export rates either directly through modification of a nuclear localization sequence or nuclear export sequence, or indirectly by affecting interactions with binding partners that alter import and export rates. Shuttling, which refers to the facilitated diffusion of Dorsal through its interaction with its cytoplasmic inhibitor Cactus, could regulate nuclear levels by delivering more Dorsal ventrally. Finally, nuclear spacing could result in higher nuclear levels by leaving fewer nuclei in the ventral domain to uptake Dorsal. This review details how each of these mechanisms may help establish Dorsal nuclear levels in the early fly embryo, which serves as a paradigm for understanding how the dynamics of graded inputs can influence patterning and target gene expression. Furthermore, careful analysis of nuclear Dorsal levels is likely to provide general insights as recent studies have suggested that the regulation of nuclear import affects the timing of gene expression at the maternal-to-zygotic transition.

Spatial arrangement, polarity, and posttranslational modifications of the microtubule system in the Drosophila eye.

We have analyzed the organization of the microtubule system in photoreceptor cells and pigment cells within the adult Drosophila compound eye. Immunofluorescence localization of tubulin and of Short stop, a spectraplakin that has been reported to be involved in the anchorage of microtubule minus ends at the membrane, suggests the presence of non-centrosomal microtubule-organizing centers at the distal tip of the visual cells. Ultrastructural analyses confirm that microtubules emanate from membrane-associated plaques at the site of contact with cone cells and that all microtubules are aligned in distal-proximal direction within the photoreceptor cells. Determination of microtubule polarities demonstrated that about 95% of the microtubules in photoreceptor cells are oriented with their plus end in the direction of the synapse. Pigment cells in the eye contain only microtubules aligned in distal-proximal direction, with their plus end pointing towards the retinal floor. There, two populations of microtubules can be distinguished, single microtubules and bundled microtubules, the latter associated with actin filaments. Whereas microtubules in both photoreceptor cells and pigment cells are acetylated and mono/bi-glutamylated on α-tubulin, bundled microtubules in pigment cells are apparently also mono/bi-glutamylated on ß-tubulin, providing the possibility of binding different microtubule-associated proteins.

Protein-coding circular RNA enhances antiviral immunity via JAK/STAT pathway in Drosophila.

RNA interference (RNAi) drives powerful antiviral immunity in plants and animals so that many viruses must express viral suppressor of RNAi (VSR) to establish virulent infection. However, little is known about the immune responses conferring resistance against viruses that have evolved the counter-defensive strategy to suppress antiviral RNAi. In this study, we discover that Drosophila cells infected with Drosophila C virus (DCV), a natural viral pathogen of Drosophila known to harbor a potent VSR, exhibit heightened expression of circular RNA circZfh1. circZfh1 confers virus resistance in the presence of viral suppression of antiviral RNAi. Furthermore, we validate that circZfh1 encodes a 274-amino acid protein, CRAV, essential for its antiviral activity. Notably, CRAV differs from its parental Zfh1 gene in a different reading frame, with the C-terminal 69 amino acids unique to CRAV. Our analysis also reveals the presence of CRAV in species within the melanogaster subgroup, with the C-terminal unique fragment undergoing accelerated evolution. Expression of CRAV upregulates the expression of the cytokine Upd3, which binds to its receptor, stimulating the JAK-STAT pathway and enhancing the immune response to DCV infection. Notably, CRISPR/Cas9 knockout of circZfh1 significantly enhances DCV replication in vitro and in vivo, with circZfh1-knockout adult flies displaying heightened disease susceptibility to DCV. In summary, our findings unveil a Drosophila protein-coding circular RNA that activates an innate immune signaling pathway crucial for virus resistance following the suppression of antiviral RNAi by viruses, thereby elucidating a novel counter-defensive strategy.IMPORTANCEEukaryotic hosts possess a complex, multilayered immune system that guards against pathogen invasion. In fruit flies, RNA interference (RNAi) drives robust antiviral immunity, prompting many viruses to express viral suppressors of RNAi (VSRs) to establish virulent infections. However, little is known about immune responses that confer resistance against viruses with potent VSRs. In this study, we discovered that Drosophila cells infected with Drosophila C virus (DCV), a natural viral pathogen possessing a potent VSR, upregulated the expression of circular RNA circZfh1. circZfh1 exhibits DCV-specific antiviral activity, encoding a 274-amino acid protein, CRAV, crucial for its antiviral effects. As a different reading frame from its parental Zfh1 gene, the C-terminal 69 amino acids are unique to CRAV, undergoing faster evolution. CRAV activates the JAK-STAT pathway, enhancing the immune response to DCV infection. Therefore, our work uncovers a new strategy for suppressing viral counter-defense through protein-coding circular RNA in fruit flies.

Drosophila appear resistant to trans-synaptic tau propagation.

Alzheimer's disease is the most common cause of dementia in the elderly, prompting extensive efforts to pinpoint novel therapeutic targets for effective intervention. Among the hallmark features of Alzheimer's disease is the development of neurofibrillary tangles comprised of hyperphosphorylated tau protein, whose progressive spread throughout the brain is associated with neuronal death. Trans-synaptic propagation of tau has been observed in mouse models, and indirect evidence for tau spread via synapses has been observed in human Alzheimer's disease. Halting tau propagation is a promising therapeutic target for Alzheimer's disease; thus, a scalable model system to screen for modifiers of tau spread would be very useful for the field. To this end, we sought to emulate the trans-synaptic spread of human tau in Drosophila melanogaster. Employing the trans-Tango circuit mapping technique, we investigated whether tau spreads between synaptically connected neurons. Immunohistochemistry and confocal imaging were used to look for tau propagation. Examination of hundreds of flies expressing four different human tau constructs in two distinct neuronal populations reveals a robust resistance in Drosophila to the trans-synaptic spread of human tau. This resistance persisted in lines with concurrent expression of amyloid-ß, in lines with global human tau knock-in to provide a template for human tau in downstream neurons, and with manipulations of temperature. These negative data are important for the field as we establish that Drosophila expressing human tau in subsets of neurons are unlikely to be useful to perform screens to find mechanisms to reduce the trans-synaptic spread of tau. The inherent resistance observed in Drosophila may serve as a valuable clue, offering insights into strategies for impeding tau spread in future studies.

Taste cells expressing Ionotropic Receptor 94e reciprocally impact feeding and egg laying in Drosophila.

Chemosensory cells across the body of Drosophila melanogaster evaluate the environment to prioritize certain behaviors. Previous mapping of gustatory receptor neurons (GRNs) on the fly labellum identified a set of neurons in L-type sensilla that express Ionotropic Receptor 94e (IR94e), but the impact of IR94e GRNs on behavior remains unclear. We used optogenetics and chemogenetics to activate IR94e neurons and found that they drive mild feeding suppression but enhance egg laying. In vivo calcium imaging revealed that IR94e GRNs respond strongly to certain amino acids, including glutamate, and that IR94e plus co-receptors IR25a and IR76b are required for amino acid detection. Furthermore, IR94e mutants show behavioral changes to solutions containing amino acids, including increased consumption and decreased egg laying. Overall, our results suggest that IR94e GRNs on the fly labellum discourage feeding and encourage egg laying as part of an important behavioral switch in response to certain chemical cues.

Glycosylation in Drosophila S2 cells.

In recent years, there has been a remarkable surge in the approval of therapeutic protein drugs, particularly recombinant glycoproteins. Drosophila melanogaster S2 cells have become an appealing platform for the production of recombinant proteins due to their simplicity and low cost in cell culture. However, a significant limitation associated with using the S2 cell expression system is its propensity to introduce simple paucimannosidic glycosylation structures, which differs from that in the mammalian expression system. It is well established that the glycosylation patterns of glycoproteins have a profound impact on the physicochemical properties, bioactivity, and immunogenicity. Therefore, understanding the mechanisms behind these glycosylation modifications and implementing measures to address it has become a subject of considerable interest. This review aims to comprehensively summarize recent advancements in glycosylation modification in S2 cells, with a particular focus on comparing the glycosylation patterns among S2, other insect cells, and mammalian cells, as well as developing strategies for altering the glycosylation patterns of recombinant glycoproteins.

Transiently restricting individual amino acids protects Drosophila melanogaster against multiple stressors.

Nutrition and resilience are linked, though it is not yet clear how diet confers stress resistance or the breadth of stressors that it can protect against. We have previously shown that transiently restricting an essential amino acid can protect Drosophila melanogaster against nicotine poisoning. Here, we sought to characterize the nature of this dietary-mediated protection and determine whether it was sex, amino acid and/or nicotine specific. When we compared between sexes, we found that isoleucine deprivation increases female, but not male, nicotine resistance. Surprisingly, we found that this protection afforded to females was not replicated by dietary protein restriction and was instead specific to individual amino acid restriction. To understand whether these beneficial effects of diet were specific to nicotine or were generalizable across stressors, we pre-treated flies with amino acid restriction diets and exposed them to other types of stress. We found that some of the diets that protected against nicotine also protected against oxidative and starvation stress, and improved survival following cold shock. Interestingly, we found that a diet lacking isoleucine was the only diet to protect against all these stressors. These data point to isoleucine as a critical determinant of robustness in the face of environmental challenges.

Pathogen infection alters the gene expression landscape of transposable elements in Drosophila melanogaster.

Transposable elements make up substantial proportions of eukaryotic genomes and many are thought to be remnants of ancient viral infections. Current research has begun to highlight the role transposable elements can play in the immune system response to infections. However, most of our knowledge about transposable element expression during infection is limited by the specific host and pathogen factors from each study, making it difficult to compare studies and develop broader patterns regarding the role of transposable elements during infection. Here, we use the tools and resources available in the model, Drosophila melanogaster, to analyze multiple gene expression datasets of flies subject to bacterial, fungal, and viral infections. We analyzed differences in pathogen species, host genotype, host tissue, and sex to understand how these factors impact transposable element expression during infection. Our results highlight both shared and unique transposable element expression patterns between pathogens and suggest a larger effect of pathogen factors over host factors for influencing transposable element expression.

High-Precision Calorimetry-Based Analysis of Pupal-Pharate Adult Development in Drosophila melanogaster.

In holometabolous insects, the larval body is almost completely decomposed and reconstructed into the adult body during the pupal-pharate adult stages. Therefore, the total energetic cost of this process is a key thermodynamic quantity necessary for evaluating the benefit of their life history. Here, we measured whole-body thermal dissipation of single pupae of the fruit fly, Drosophila melanogaster, during the period from puparium formation to adult eclosion as a function of age, using a high-precision isothermal calorimeter at T = 298 K. The mass-specific energy consumption during the period from the onset of larval-pupal apolysis to adult eclosion was determined to be 2.3 kJ/g for an individual of mass (adult) = 1.0 mg, while it was observed to follow Kleiber's law for individuals smaller than mass (adult) = 1.0 mg. During the pupal-pharate adult period, in addition to the U-shaped variation, several characteristic thermal dissipations related to various events, including somatic muscle contractions, ecdyses, pulsatile hormone secretion in a pharate adult, and vaporization of the exuvial fluid, were observed. The periodic bursts in the pharate adult stage grew exponentially, suggesting that the positive feedback in the metabolic system synchronized with the progression of development, making the energy consumption in this stage more efficient. The present study showed that high-precision calorimetry is a powerful and credible method for measuring not only the total energy spent during development but also the energy spent during every specific developmental event in an organism.

Unveiling the cell dynamics during the final shape formation of the tarsus in Drosophila adult leg by live imaging.

Organisms display a remarkable diversity in their shapes. Although substantial progress has been made in unraveling the mechanisms that govern cell fate determination during development, the mechanisms by which fate-determined cells give rise to the final shapes of organisms remain largely unknown. This study describes in detail the process of the final shape formation of the tarsus, which is near the distal tip of the adult leg, during the pupal stage in Drosophila melanogaster. Days-long live imaging revealed unexpectedly complicated cellular dynamics. The epithelial cells transiently form the intriguing structure, which we named the Parthenon-like structure. The basal surface of the epithelial cells and localization of the basement membrane protein initially show a mesh-like structure and rapidly shrink into the membranous structure during the formation and disappearance of the Parthenon-like structure. Furthermore, macrophage-like cells are observed moving around actively in the Parthenon-like structure and engulfing epithelial cells. The findings in this research are expected to significantly contribute to our understanding of the mechanisms involved in shaping the final structure of the adult tarsus.

A novel insertional allele of the CG18135 gene is associated with severe mutant phenotypes in Drosophila melanogaster.

Drosophila melanogaster has been at the forefront of genetic studies and biochemical modeling for over a century. Yet, the functions of many genes are still unknown, mainly because no phenotypic data are available. Herein, we present the first evidence data regarding the particular molecular and other quantifiable phenotypes, such as viability and anatomical anomalies, induced by a novel P{lacW} insertional mutant allele of the CG18135 gene. So far, the CG18135 functions have only been theorized based on electronic annotation and presumptive associations inferred upon high-throughput proteomics or RNA sequencing experiments. The descendants of individuals harboring the CG18135 P{lacW}CG18135 allele were scored in order to assess mutant embryonic, larval, and pupal viability versus Canton Special (CantonS). Our results revealed that the homozygous CG18135 P{lacW}CG18135 /CG18135 P{lacW}CG18135 genotype determines significant lethality both at the inception of the larval stage and during pupal development. The very few imago escapers that either breach or fully exit the puparium exhibit specific eye depigmentation, wing abnormal unfolding, strong locomotor impairment with apparent spasmodic leg movements, and their maximum lifespan is shorter than 2 days. Using the quantitative real-time PCR (qRT-PCR) method, we found that CG18135 is upregulated in male flies, but an unexpected gene upregulation was also detected in heterozygous mutants compared to wild-type flies, probably because of regulatory perturbations induced by the P{lacW} transposon. Our work provides the first phenotypic evidence for the essential role of CG18135, a scenario in accordance with the putative role of this gene in carbohydrate-binding processes.

Fly Me to the Micron: Microtechnologies for Drosophila Research.

Multicellular model organisms, such as Drosophila melanogaster (fruit fly), are frequently used in a myriad of biological research studies due to their biological significance and global standardization. However, traditional tools used in these studies generally require manual handling, subjective phenotyping, and bulk treatment of the organisms, resulting in laborious experimental protocols with limited accuracy. Advancements in microtechnology over the course of the last two decades have allowed researchers to develop automated, high-throughput, and multifunctional experimental tools that enable novel experimental paradigms that would not be possible otherwise. We discuss recent advances in microtechnological systems developed for small model organisms using D. melanogaster as an example. We critically analyze the state of the field by comparing the systems produced for different applications. Additionally, we suggest design guidelines, operational tips, and new research directions based on the technical and knowledge gaps in the literature. This review aims to foster interdisciplinary work by helping engineers to familiarize themselves with model organisms while presenting the most recent advances in microengineering strategies to biologists.

Restoring galactose metabolism without restoring GALT rescues both compromised survival in larvae and an adult climbing deficit in a GALT-null D. Melanogaster model of classic galactosemia.

Classic galactosemia (CG) is an autosomal recessive disorder that results from profound deficiency of galactose-1-phosphate uridylyltransferase (GALT), the middle enzyme in the highly conserved Leloir pathway of galactose metabolism. That galactose metabolism is disrupted in patients with CG, and in GALT-null microbial, cell culture, and animal models of CG, has been known for many years. However, whether the long-term developmental complications of CG result from disrupted galactose metabolism alone, or from loss of some independent moonlighting function of GALT, in addition to disrupted galactose metabolism, has been posed but never resolved. Here, we addressed this question using a GALT-null Drosophila melanogaster model of CG engineered to express uridine diphosphate (UDP)-glucose/galactose pyrophosphorylase (UGGP), a plant enzyme that effectively bypasses GALT in the Leloir pathway by converting substrates uridine triphosphate (UTP) plus galactose-1-phosphate (gal-1P) into products UDP-galactose plus pyrophosphate (PPi). While GALT and UGGP share one substrate (gal-1P) and one product (UDP-galactose), they are structurally and evolutionarily unrelated enzymes. It is therefore extremely unlikely that they would also share a moonlighting function. We found that GALT-null flies expressing UGGP showed not only partial rescue of metabolic abnormalities and acute larval sensitivity to dietary galactose, as expected, but also full rescue of an adult motor deficit otherwise seen in this model. By extension, these results may offer insights to the underlying bases of at least some acute and long-term complications experienced by patients with CG.

Beyond Simple vs Complex: Exploring the Nuanced and Unexpected Effects of Spatial Environmental Complexity on Mating Patterns and Female Fecundity.

The features of the physical environment set the stage upon which sexual selection operates, and consequently can have a significant impact on variation in realized individual fitness, and influence a population's evolutionary trajectory. This phenomenon has been explored empirically in several studies using fruit flies (Drosophila melanogaster) which have found that changing the spatial complexity of the mating environment influenced male-female interaction dynamics, (re)mating rates and realized female fecundities. However, these studies did not explore mating patterns, which can dramatically alter the genetic composition of the next generation, and frequently only compared a single, small "simple" environment to a single larger "complex" environment. While these studies have shown that broadly changing the characteristics of the environment can have big effects on reproductive dynamics, the plasticity of this outcome to more subtle changes has not been extensively explored. Our study set out to compare patterns of mating and courtship between large- and small-bodied males and females, and female fecundities in both a simple environment and two distinctly different spatially-complex environments. We found that realized offspring production patterns differed dramatically between all three environments, indicating that the effects of increasing spatial complexity on mating outcomes are sensitive to the specific type of environmental complexity. Furthermore, we observed female fecundities were higher for flies in both complex environments compared those in the simple environment, supporting its role as a mediator of sexual conflict. Together, these results show that the union of gametes within a population can be greatly influenced by the specific spatial features of the environment and that while some outcomes of increased environmental complexity are likely generalizable, other phenomena like mating patterns and courtship rates may vary from one complex environment to another.

The Aromatic Scents of Four Plants in Learning and Memory of Drosophila melanogaster.

Introduction: Folkloric claims have surrounded essential oils, including their enhancement of learning and memory through inhalational exposure. Few studies in humans have shown a benefit in cognition, albeit incremental. However, this benefit may not be entirely attributable to the essential oil aroma but may be confounded by psychological associations. We investigated rosemary, peppermint, lemon, and coffee aromas in a learning and memory model of Drosophila melanogaster to eliminate this confounder. Methods: We screened for concentrations of the four treatments that are non-stimulatory for altered locomotory behavior in the flies. At these concentrations, we determined if they were chemoneutral (i.e., neither chemoattractant nor chemorepellent) to the flies. Learning and memory of the flies exposed to these aromas were determined using an Aversive Phototaxis Suppression (APS) assay. Results: The aromas of rosemary, peppermint, and lemon that did not elicit altered mobility in the flies were from dilute essential oil solutions that ranged from 0.2 to 0.5% v/v; whereas for the aroma in coffee, it was at a higher concentration of 7.5% m/v. At these concentrations, the aromas used were found to be chemoneutral towards the flies. We observed no improvement in both learning and memory in the four aromas tested. While a significant reduction (p < 0.05) in learning was observed when flies were treated with the aromas of rosemary, peppermint, and coffee, a significant reduction (p < 0.05) in memory was only observed in the peppermint aroma treatment. Conclusion: This study demonstrated that in the absence of psychological association, the four aromas do not enhance learning and memory.

Magainin-AM2 inhibits sucrose-induced hyperglycaemia, oxidative stress, and cognitive dysfunction in Drosophila melanogaster.

Hyperglycaemia-induced oxidative stress plays significant roles in the development of type 2 diabetes and its complications. This study investigates effects of magainin-AM2 on high-sucrose diet induced redox imbalance and cognitive impairment in Drosophila melanogaster. Effects of various concentrations of sucrose, magainin-AM2 or a combination of both agents on mortality, eclosion rate, generation of reactive oxygen and nitrogen species, activities of antioxidant enzymes, thiol system, and markers of cognitive functions in control and treated flies were examined. Results showed that the exposure of flies to high sucrose (30% - 60% w/w) diet increased mortality rate (38 - 67%, P<0.001) and levels of glucose (1.8 - 1.9-fold, P<0.001), hydrogen peroxide (1.4 - 1.5-fold, P<0.01) and nitrite/nitrate (1.2-fold, P<0.01). Decreased levels of total thiol (53 - 59%, P<0.01), non-protein thiols (59 - 63%, P<0.01), catalase activities (39 - 47%, P<0.01 -0.05) and glutathione-s-transferase activities (31 - 43%, P<0.01 - 0.05) were also observed. Magainin-AM2 (0 - 10 µM/kg diet) did not affect fly mortality rate, levels of hydrogen peroxide and nitrite/nitrate, and activities of catalase and glutathione-s-transferase. However, the peptide produced a dose-dependent increase in total thiol 1.2 - 1.6-fold, P<0.001-0.01)and increases non-protein thiol levels at 10µM/kg diet (2.0-fold, P<0.01). Magainin-AM2 inhibited sucrose-induced elevation of glucose (55 - 70%, P<0.001), hydrogen peroxide (11 - 12%, P<0.01) and nitrite/nitrate (20 - 34%, P<0.01 - 0.05). The peptide prevented sucrose-induced reduction in total and non-protein thiols (1.9 - 2.0-fold, P<0.05) levels and activities of catalase (2.3 - 3.1-fold, P<0.001) and glutathione-s-transferase (1.8 - 2.8-fold, P<0.001- 0.05). Magainin-AM2 inhibited sucrose-induced reduction in acetylcholinesterase activities (3.6 - 4.0-fold, P<0.001), eclosion rate (18%, P<0.001) and negative geotaxis (1.3 - 14-fold, P<0.001). These results indicate that beneficial actions of magainin-AM2 may also involve the prevention of hyperglycaemia-induced oxidative damage and encourage its further development as an anti-diabetic agent.