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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]