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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. [Display omitted] • This study first time report nephroprotective role of hsp27 in Cd induce renal toxicity in MTs of the D. melanogaster larvae. • This study first time report nephroprotective role of hsp27 in Cd induce renal toxicity in MTs of the D. melanogaster larvae. • hsp27 overexpression restores MMP, ATP level and microvilli brush border density in MTs of Cd exposed D. melanogaster larvae. • hsp27 knockdown negatively alter MTs functions in D. melanogaster larvae and more severely affect after the Cd exposure. [ABSTRACT FROM AUTHOR]

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]

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. Image 1 • High sucrose diet (HSD) causes type 2 diabetes mediated Malpighian tubules (MTs) dysfunction in Drosophila. • HSD causes oxidative stress, apoptosis and advance glycation end products (AGE) accumulation in MTs. • HSD causes increased uric acid level, reduced expression of transporters and fluid secretion rate. • HSD causes perturbations in ECM, AGE-RAGE and TGF-β pathways in MTs. • HSD causes increased expression of Viking and Collagen 4 A1 that led to fibrosis in MTs. [ABSTRACT FROM AUTHOR]

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. Unlabelled Image • Assessment and comparison of cellular and progressive toxicity CNPs was carried out. • Exposure to CNPs and CNTs did not affect the developmental period of the larvae. • Reproductive performance was significantly diminished in case of CNPs conversely. • Exposure to CNPs and CNTs cause a moderate level of cytotoxicity in Drosophila. • Inexpensive CNPs may use as an alternative of expensive CNTs for biomedical uses. [ABSTRACT FROM AUTHOR]