The fruit fly kidney stone models and their application in drug development

Wang, Shiyao; Ju, Yingjie; Gao, Lujuan; Miao, Yaodong; Qiao, Hui; Wang, Yiwen

doi:10.1016/j.heliyon.2022.e09232

Cited by 5 publications

(5 citation statements)

References 63 publications

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“…For instance, A. protuberus and A. ochraceus shortened the insect lifespan to 25 days, while A. japonicus and A. sydowii produced 100% mortality in the model organism after 30 days (Figure 5). Aspergillus versicolor, Aspergillus sp., A. westerdijkiae, and A. oryzae showed a similar shortening effect on Drosophila lifespan (18,19,20, and 21 days, respectively). Aspergillus proliferans, A. flavus, and A. nidulans produced a similar effect by reducing the fruit fly lifespan to 27, 28, and 29 days, respectively.…”

Section: Pathogenicity Of Aspergillus Fungi On Fruit Fliesmentioning

confidence: 76%

“…The Drosophila melanogaster model has been recently used to analyze various human medical issues. For instance, a recent study performed by Wang et al [ 18 ] showed that the Malpighian tubules in the renal system of fruit flies are similar to the mammalian renal tubules in both function and structure, pointing out that the kidney stone models of the fruit flies can supply quicker, cost-limited, and high-throughput screening platforms for the development of novel drugs to treat kidney stones [ 15 ]. Fruit flies have become an excellent model for cost-effectively and expediently studying nutrient-sensing pathways and metabolic homeostasis [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…For instance, a recent study performed by Wang et al [ 18 ] showed that the Malpighian tubules in the renal system of fruit flies are similar to the mammalian renal tubules in both function and structure, pointing out that the kidney stone models of the fruit flies can supply quicker, cost-limited, and high-throughput screening platforms for the development of novel drugs to treat kidney stones [ 15 ]. Fruit flies have become an excellent model for cost-effectively and expediently studying nutrient-sensing pathways and metabolic homeostasis [ 18 , 19 ]. In a study conducted by Rani et al [ 20 ], Malpighian tubules of Drosophila were used as a model to investigate the effects of chronic exposure to a high-sugar diet on renal tubules [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Pathogenicity of Aspergillus Airborne Fungal Species Collected from Indoor and Outdoor Public Areas in Tianjin, China

Nafis,

Quach,

Al-Shaarani

et al. 2023

Pathogens

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Airborne fungi play an important role in air pollution and may have various negative effects on human health. In particular, Aspergillus fungi are pathogenic to humans and several domestic animals. In this work, Aspergillus strains isolated from airborne fungal communities sampled from different indoor and outdoor environments in Tianjin University were tested for pathogenicity on Drosophila melanogaster. Airborne fungi were sampled using an HAS-100B air sampler, over a one-year sampling period. Isolated fungal strains were identified based on morphological and molecular analysis. The Aspergillus-centered study was conducted as part of a larger work focusing on the total airborne fungal community in the analyzed environments, which yielded 173 fungal species. In this context, the genus Aspergillus showed the second-highest species richness, with 14 isolated species. Pathogenicity tests performed on male adults of Drosophila melanogaster through a bodily contact bioassay showed that all analyzed airborne Aspergillus species were pathogenic to fruit flies, with high insect mortality rates and shortened lifespan. All the studied fungi induced 100% mortality of fruit flies within 30 culture days, with one exception constituted by A. creber (39 days), while the shortest lifespan (17 days) was observed in fruit flies treated with A. tubingensis. Our results allow us to hypothesize that the studied airborne fungal species may have a pathogenic effect on humans, given the affinity between fruit flies and the human immune system, and may help to explain the health risk linked with Aspergillus fungi exposure in densely populated environments.

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Section: Pathogenicity Of Aspergillus Fungi On Fruit Fliesmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pathogenicity of Aspergillus Airborne Fungal Species Collected from Indoor and Outdoor Public Areas in Tianjin, China

Nafis,

Quach,

Al-Shaarani

et al. 2023

Pathogens

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show abstract

“…Fan et al used fruit flies to perform RNAi knockdown of nephrolithiasis-related genes in the principal cells of Malpighian tubules, and studied the effects of antilithic agents on CaOx crystal formation [ 18 ]. Therefore, genetic studies of stone disease in fruit flies may have future potential [ 21 , 22 , 23 ]. The pathogenesis of CaOx formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention.…”

Section: Discussionmentioning

confidence: 99%

Astragalus membranaceus Extract Prevents Calcium Oxalate Crystallization and Extends Lifespan in a Drosophila Urolithiasis Model

Chen

Dalanbaatar

Chen

et al. 2022

Life

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Approximately 1 in 20 people develops kidney stones at some point in their life. Although the surgical removal of stones is common, the recurrence rate remains high and it is therefore important to prevent the occurrence of kidney stones. We chose Astragalus membranaceus (AM), which is a traditional Chinese medicine, to study the prevention of urolithiasis using a Drosophila model based on our previous screening of traditional Chinese herbs. Wild-type Drosophila melanogaster Canton-S adult fruit flies were used in this study. Ethylene glycol (EG, 0.5%) was added to food as a lithogenic agent. The positive control agent (2% potassium citrate (K-citrate)) was then compared with AM (2, 8, and 16 mg/mL). After 21 days, the fruit flies were sacrificed under carbon dioxide narcotization, and the Malpighian tubules were dissected, removed, and processed for polarized light microscopy examination to observe calcium oxalate (CaOx) crystallization. Then, the ex vivo dissolution of crystals in the Malpighian tubules was compared between K-citrate and AM. Survival analysis of the EG, K-citrate, and AM groups was also performed. Both 2% K-citrate and AM (16 mg/mL) significantly inhibited EG-induced CaOx crystal formation. Mean lifespan was significantly reduced by the administration of EG, and the results were significantly reversed in the AM (8 and 16 mg/mL) groups. However, AM extract did not directly dissolve CaOx crystals in Drosophila Malpighian tubules ex vivo. In conclusion, AM extract decreased the ratio of CaOx crystallization in the Malpighian tubules and significantly ameliorated EG-induced reduction of lifespan. AM prevented CaOx crystal formation in the Drosophila model.

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“…The advantages lie in the easy and cost-effective insect rearing, the availability of suitable genetic mutants or transgenic strains and the exemption of experiments involving insects from ethical standards governing the use of animals for scientific purposes [ 8 , 9 , 10 ]. One such example is the study of Drosophila melanogaster (Diptera: Drosophilidae) MTs as a model for investigating the etiology of kidney crystal formation, exploring possible pharmacological treatments for stone disease [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Developmental and Nutritional Dynamics of Malpighian Tubule Autofluorescence in the Asian Tiger Mosquito Aedes albopictus

Croce,

Garbelli,

Moyano

et al. 2023

IJMS

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Malpighian tubules (MTs) are arthropod excretory organs crucial for the osmoregulation, detoxification and excretion of xenobiotics and metabolic wastes, which include tryptophan degradation products along the kynurenine (KYN) pathway. Specifically, the toxic intermediate 3-hydroxy kynurenine (3-HK) is metabolized through transamination to xanthurenic acid or in the synthesis of ommochrome pigments. Early investigations in Drosophila larval fat bodies revealed an intracellular autofluorescence (AF) that depended on tryptophan administration. Subsequent observations documented AF changes in the MTs of Drosophila eye-color mutants genetically affecting the conversion of tryptophan to KYN or 3-HK and the intracellular availability of zinc ions. In the present study, the AF properties of the MTs in the Asian tiger mosquito, Aedes albopictus, were characterized in different stages of the insect’s life cycle, tryptophan-administered larvae and blood-fed adult females. Confocal imaging and microspectroscopy showed AF changes in the distribution of intracellular, brilliant granules and in the emission spectral shape and amplitude between the proximal and distal segments of MTs across the different samples. The findings suggest AF can serve as a promising marker for investigating the functional status of MTs in response to metabolic alterations, contributing to the use of MTs as a potential research model in biomedicine.

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The fruit fly kidney stone models and their application in drug development

Cited by 5 publications

References 63 publications

Pathogenicity of Aspergillus Airborne Fungal Species Collected from Indoor and Outdoor Public Areas in Tianjin, China

Pathogenicity of Aspergillus Airborne Fungal Species Collected from Indoor and Outdoor Public Areas in Tianjin, China

Astragalus membranaceus Extract Prevents Calcium Oxalate Crystallization and Extends Lifespan in a Drosophila Urolithiasis Model

Developmental and Nutritional Dynamics of Malpighian Tubule Autofluorescence in the Asian Tiger Mosquito Aedes albopictus

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