The primary aim of this study was to analyse the influence of honeybee venom on various aspects of Drosophila melanogaster physiology and to assess the efficacy of adipokinetic hormone (AKH) in mitigating venom toxicity. We examined the harmful effects of venom on the thoracic muscles and central nervous system of Drosophila, as well as the potential use of AKH to counteract these effects. The results demonstrated that envenomation altered AKH levels in the Drosophila CNS, promoted cell metabolism, as evidenced by an increase in citrate synthase activity in muscles, and improved relative cell viability in both organs incubated in vitro. Furthermore, venom treatment reduced the activity of two key antioxidative stress enzymes, superoxide dismutase and catalase, and modified the expression of six genes encoding immune system components (Keap1, Relish, Nox, Eiger, Gadd45, and Domeless) in both organs. The venom also disrupted muscle cell ultrastructure, specifically myofibrils, and increased the release of arginine kinase into the incubation medium. Notably, when administered alongside the venom, AKH influenced the majority of these changes. AKH was the most effective in minimising damage to the ultrastructure of muscle cells and preventing the release of arginine kinase from muscles to the medium; however, in other parameters, the effect was modest or minimal. Given that honeybee venom often affects humans, understanding its actions and potential ways to reduce or eliminate them is valuable and could lead to the development of pharmacologically important compounds that may have clinical relevance.

• Keywords
• Adipokinetic hormone, Arginine kinase, Bee venom, Drosophila model, Immune responsible genes, Muscle structure,
• MeSH
• Central Nervous System drug effects   metabolism   MeSH
• Drosophila melanogaster drug effects   metabolism   MeSH
• Insect Hormones * pharmacology   metabolism   MeSH
• Pyrrolidonecarboxylic Acid * analogs & derivatives   pharmacology   metabolism   MeSH
• Oligopeptides * pharmacology   metabolism   MeSH
• Bee Venoms * toxicity   antagonists & inhibitors   MeSH
• Bees MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• adipokinetic hormone MeSH Browser
• Insect Hormones * MeSH
• Pyrrolidonecarboxylic Acid * MeSH
• Oligopeptides * MeSH
• Bee Venoms * MeSH

The neurotransmitter dopamine (DA) is known to be involved in a multitude of physiological processes. We investigated sexually dimorphic effects of disruptions in DA homeostasis and its relationship to senescence using three different Drosophila melanogaster mutants namely Catsup (Catsup26 ) with elevated DA levels, and pale (ple2 ), Punch (PuZ22 ) with depleted DA levels. In all genotypes including controls, DA levels were significantly lower in old (45-50-day-old) flies compared with young (3-5-day-old) in both sexes. Interestingly, females had lower DA content than males at young age whereas this difference was not observed in old age, suggesting that males had a larger decline in DA levels with age. Females, in general, were longer lived compared with males in all genotypes except ple2 mutants with depleted DA levels. This phenotype was abolished in the ple2 rescue flies. Interestingly, females also demonstrated marked age-related decline in circadian locomotor activity compared with males. Old Catsup26 males with elevated DA levels accumulated significantly lower levels of lipid peroxidation product 4-hydroxy 2-nonenal (4-HNE) compared with age-matched wild type, ple2 and PuZ22 mutant males. In Catsup26 revertant lines this phenomenon was absent. We also observed a sexually dimorphic response in the expression levels of key stress and aging associated and/or related transcription factor genes across genotypes with elevated or depleted DA levels which was reverted to wild type levels in specific rescue lines. Taken together, our results reveal a novel sexually dimorphic involvement of DA in senescence characteristics of D. melanogaster.

• Keywords
• 4-hydroxynonenal, aging, circadian rhythms, lifespan, protein carbonyl,
• MeSH
• Circadian Clocks MeSH
• Dopamine genetics   metabolism   MeSH
• Drosophila melanogaster MeSH
• Genotype MeSH
• Homeostasis * MeSH
• Locomotion MeSH
• Lipid Peroxidation MeSH
• Drosophila Proteins genetics   metabolism   MeSH
• Sex Factors MeSH
• Aging genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Names of Substances
• catsup protein, Drosophila MeSH Browser
• Dopamine MeSH
• Drosophila Proteins MeSH