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Cadmium (Cd) exposure to the animals including humans is reported as nephrotoxic compounds i.e., disturbing redox status (increase oxidative stress), mitochondrial dysfunction, renal cell death and altered transporters in the renal system. Hsp27 (a small heat shock protein) has been shown as one of the modulators in the renal dysfunction and increased against the Cd induced toxicity. However, no studies are reported on the genetic modulation of stress protein against the Cd-induced nephrotoxicity. The current study aimed to examine the protective role of hsp27 overexpression against the Cd-induced nephrotoxicity using Drosophila melanogaster as an animal model. D. melanogaster renal system includes nephrocytes and Malpighian tubules (MTs) that show the functional similarity with mammalian kidney nephron. Overexpression of the hsp27 was found to reduce the Cd induced oxidative stress, rescue cell death in MTs of Cd exposed D. melanogaster larvae. The rescued GSH level, NADPH level and glucose 6 phosphate dehydrogenase (G6PD) activity were also observed in the MTs of the Cd exposed organism. Function (efflux activity and fluid secretion rate) of the MTs was restored in Cd exposed hsp27 overexpressed larvae. Further, results were confirmed by restored brush border microvilli density and reduced uric acid level. Tissue specific knockdown of hsp27 developed Cd like phenotypes in MTs and the phenotypes enhanced in Cd exposed condition. The present study clearly shows the role of hsp27 overexpression in restoration of the MTs function and protection against the Cd induced renal toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Continuous feeding of high dietary sugar is strongly associated with type 2 diabetes (T2D) and its secondary complications. Diabetic nephropathy (DN) is a major secondary complication that leads to glomerular and renal tubular dysfunction. The present study is aimed to investigate the effects of chronic exposure of high sugar diet (HSD) on renal tubules. Malpighian tubules (MTs), a renal organ of Drosophila, were used as a model in the study. Feeding of HSD develops T2D condition in Drosophila. The MTs showed structural abnormalities in 20 days of HSD fed flies. Impaired insulin signaling, oxidative stress, enhanced levels of AGE-RAGE and induction of apoptosis were observed in the MTs of these flies. Further, altered expression of transporters, enhanced uric acid level and reduced fluid secretion rate confirmed the impaired function of MTs in these flies. RNA-seq and RT-PCR analyses in the MTs of HSD fed-and control-flies revealed the altered expression of candidate genes that regulate several important pathways including extracellular matrix (ECM), advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), transforming growth factor β (TGF-β), galactose, starch and sucrose metabolism that are well known mediators of renal tubular dysfunction in DN patients. Disruption of insulin signaling in the MTs also causes renal tubular dysfunction similar to HSD fed flies. Overall, the study suggests that phenotypes observed in the MTs of HSD fed flies recapitulate several hallmarks of renal tubular dysfunction in DN patients. Therefore, we conclude that MTs of HSD fed flies may be used for deciphering the underlying mechanisms of T2D mediated renal tubular dysfunction., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Xenobiotic mediated renal toxicity is one of the major health concerns to the organisms, including humans. New chemicals with nephrotoxic potential are continuously being added to the list of existing nephrotoxicants. To predict the nephrotoxicity of these new chemicals, reliable and cost-effective alternative animal models are required. It is a prerequisite for the identification and assessment of these compounds as potential nephrotoxicants to prevent renal toxicity in the exposed population. Drosophila melanogaster, a genetically tractable invertebrate animal model, has a renal system functionally analogous to humans. The Malpighian tubules (MTs) of D. melanogaster are similar to the tubular part of nephron of the human kidney. Besides, it recapitulates the renal toxicity hallmark with mammals when exposed to known nephrotoxicants. In this study, first instar larvae of D. melanogaster (Oregon R) were exposed to different concentrations of two well-known nephrotoxicants, cadmium (Cd) and mercury (Hg). Akin to higher organisms, Cd and Hg exposure to D. melanogaster produce similar phenotypes. MTs of exposed D. melanogaster larvae exhibited increased oxidative stress, activated cellular antioxidant defense mechanism, GSH depletion, increased cleaved caspase-3 expression, increased DEVDase activity and increased cell death. The functional status of MTs was assessed by fluid secretion rate (FSR), efflux activity of transporter protein, mitochondrial membrane potential (MMP), ATP level and expression of junctional protein (Dlg). All the phenotypes observed in MTs of D. melanogaster larvae recapitulate the phenotypes observed in higher organisms. Increased uric acid level, the hallmark of renal dysfunction, was also observed in exposed larvae. Taken together, the study suggests that MTs of D. melanogaster may be used as a functional model to evaluate xenobiotic mediated nephrotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The biomedical demand of the nanomaterials is continuously increasing due to their wide range of applications in the field. However, before the implementation of these nanomaterials, toxicity assessment is essential for its safe usage. In the present study, the toxicity of carbon nanoparticles (CNPs) was investigated which was derived from candle soot and compared with commercially available multi-walled carbon nanotubes (CNTs) by using Drosophila melanogaster as a model system. First instar Drosophila larvae were exposed to CNPs as well as CNTs, and the toxic effects of these nanomaterials were compared. The result shows that both nanomaterials enhance the level of reactive oxygen species and oxidative stress in the Drosophila, which leads to the upregulation of heat shock proteins that may cause cytotoxicity in exposed Drosophila larvae. In contrast, exposure to CNPs and CNTs did not affect the developmental period of the larvae. Morphology of the internal organs, brain, gut and Malpighian tubules was also not altered in the exposed larvae. Similarly, no change observed in the cytoskeleton (F-actin) of these organs. Reproductive performance was slightly reduced in the case of CNPs compare to control. However, CNTs exposure did not show any significant effect on the reproductive performance of the flies that emerged from exposed larvae in comparison to control. Hence the study concludes that exposure to CNPs and CNTs cause a moderate level of cytotoxicity in Drosophila. The study also indicates that the inexpensive CNPs may use as an alternative to expensive CNTs for biomedical and biological applications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetic nephropathy is one of the major causes of kidney failure, accounting for ~44% of all cases. In spite of the significant mortality rate of diabetic nephropathy, specific and effective treatment is still eluding. Identification of genetic determinants and understanding their role in the progression of disease are essential for developing diagnostic tools and effective therapy. Drosophila melanogaster is a genetically tractable model organism and is being used for understanding the genetic basis of several human diseases. Drosophila has a well developed renal system and shares conserved developmental and functional processes with humans. Apart from similarities in renal system, type 1 and type 2 diabetes can be induced in Drosophila following mechanisms similar to those in human. This review discusses the current therapies available for diabetic nephropathy and examines the potential of Drosophila renal system as a model for identifying drug targets for diabetic nephropathy and screening of the potential drugs for their efficacy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Malpighian tubules are the osmoregulatory and detoxifying organs of Drosophila and its proper development is critical for the survival of the organism. They are made up of two major cell types, the ectodermal principal cells and mesodermal stellate cells. The principal and stellate cells are structurally and physiologically distinct from each other, but coordinate together for production of isotonic fluid. Proper integration of these cells during the course of development is an important pre-requisite for the proper functioning of the tubules. We have conclusively determined an essential role of ecdysone hormone in the development and function of Malpighian tubules. Disruption of ecdysone signaling interferes with the organization of principal and stellate cells resulting in malformed tubules and early larval lethality. Abnormalities include reduction in the number of cells and the clustering of cells rather than their arrangement in characteristic wild type pattern. Organization of F-actin and β-tubulin also show aberrant distribution pattern. Malformed tubules show reduced uric acid deposition and altered expression of Na(+)/K(+)-ATPase pump. B2 isoform of ecdysone receptor is critical for the development of Malpighian tubules and is expressed from early stages of its development., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Drosophila development is a tightly regulated process involving metamorphosis of a relatively less mobile larva to a highly motile adult, triggered by secretion of 20-hydroxyecdysone. Under the influence of ecdysone, most of the larval tissues degenerate, while the imaginal cells differentiate and form adult specific structures. Although the larval Malpighian tubules do not seem to be affected by ecdysone during metamorphosis, we show that ecdysone signaling plays an important role in the early development and functioning of Malpighian tubules. Disruption of ecdysone receptor function, using targeted expression of dominant negative ecdysone receptor in stellate cells, results in disruption of organization of Malpighian tubules. The number of stellate cells is reduced in such Malpighian tubules. Further, they get clustered rather than distributed in their characteristic wild type pattern. We also demonstrate that expression of Drosophila integrin protein (DRIP), an aquaporin responsible for trans-cellular water transport, is also reduced in stellate cells when ecdysone signaling is disrupted. Our results show that of the three ecdysone receptor isoforms, only EcR-B2 rescues these phenotypes. A similar pattern of stellate cell clustering and reduced expression of DRIP is observed in ecd(1), a temperature sensitive mutant, under non-permissive conditions. These results suggest that ecdysone signaling is required for proper patterning and functioning of stellate cells and that EcR-B2 may be the primary isoform required for ecdysone signaling in stellate cells.

In the present study, effect of exposure of bisphenol A (BPA) and combined exposure of BPA + HSD has been investigated on the glucose homeostasis and associated renal complications in Drosophila. Exposure of 1.0 mM BPA alone induced type 2 diabetes like condition (T2D) in adult male D. melanogaster via oxidative stress. Elevated TGF-β signaling was evident by increased expression of baboon (babo) in BPA exposed organism that stimulated the modulation of extracellular matrix (ECM) component collagen IV resulting in the fibrosis of the Malpighian tubules (MTs). Combined exposure of BPA + HSD (high sucrose diet) resulted in the increased magnitude of T2D and MTs dysfunction parameters. Taken together, the study illustrates that BPA has diabetogenic potential in exposed Drosophila that caused adverse effects on their MTs and combined exposure with BPA and HSD could aggravate the renal tubular dysfunction. The study further suggests the use of Drosophila model to study the environmental chemicals induced diabetes mediated renal dysfunction. [Display omitted] • Bisphenol A (BPA) induces type 2 diabetes (T2D) like condition in Drosophila. • BPA induced oxidative stress results in fibrosis of Malpighian tubules (MTs). • Fibrosis in the MTs results in the structural deformities in them. • Structural deformities result in reduced function of MTs and shortened life span of Drosophila. • BPA + high sucrose diet (HSD) further increased the magnitude of T2D and MTs dysfunction parameters. [ABSTRACT FROM AUTHOR]