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Dehydrozingerone ameliorate renal structures compromised in diabetic nephropathy

ABSTRACT: Dehydrozingerone ameliorate renal structures compromised in diabetic nephropathy

PROVIDER: PRJNA1227926 | ENA |

REPOSITORIES: ENA

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Dehydrozingerone ameliorate renal structures compromised in diabetic nephropathy

Project description:Kidney structural integrity is critical for bodily excretory mechanism. Diabetes has been considered as one of the major risk factors for chronic kidney disease, but the underlying mechanism remains elusive. The present study investigates the transcriptomic and proteomic profiling of long-term impact of high-fat diet (HFD) on renal tissue in mice and role of dehydrozingerone (DH) in reinstating the normal kidney function. Animals were divided into four groups- healthy (NCD+Veh), diabetic (HFD-STZ+Veh), healthy+DH (NCD+Veh+DH) and treatment (HFD-STZ+DH). 65th days of HFD-fed C57BL/6 mice developed diabetes and kidney dysfunction evident by albuminuria, proteinuria, and glucotoxicity with accumulation of glucose, triglyceride, cholesterol, albumin, and total protein in blood serum. The HFD-fed kidney showed renal injuries, including prominent defects in the glomerular filtration system by downregulation of proteins involved in transport, metabolic process, energy production, anti-oxidation, etc. Downregulation of lipid metabolism is the most impacted metabolic process under diabetic condition. Downregulation of transport proteins mainly impact the functioning of podocytes, cell adhesion and cytoskeletal rearrangement. HFD feeding also increased oxidative stress and induced mitochondrial dysfunction, and thereby activating the pro-apoptotic pathway. Progression of DNA damage under diabetic condition triggered the epigenetic alteration and subsequent downstream changes which is evident by activation of HDAC1 under diseased condition. Transcriptomic study revealed the potential of dehydrozingerone in attenuating the diabetic condition by positively regulating transport system, mitochondrial function, lipid metabolism, DNA damage and epigenetic alteration, and oxidative stress, which ameliorate the kidney function.

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