Cobalt treatment does not prevent glomerular morphological alterations in type 1 diabetic rats
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Early renal morphological alterations including glomerular hypertrophy and mesangial expansion occur in diabetic kidney disease and correlate with various clinical manifestations of diabetes. The present study was designed to investigate the influence of pharmacological modulation of HIF-1α (hypoxia inducible factor-1 alpha) protein levels, on these glomerular changes in rodent model of type 1 diabetes. Male wistar rats were made diabetic (Streptozotocin 45 mg/kg; i.p.) and afterwards treated with HIF activator cobalt chloride for 4 weeks. Renal function was assessed by serum creatinine, albumin, proteinuria levels, oxidative stress: reduced glutathione levels and catalase activity, and renal tissue HIF-1α protein levels were determined by ELISA assay. Histological analysis of kidney sections was done by haematoxylin and eosin (glomeruli diameter), periodic acid Schiff (mesangial expansion and glomerulosclerosis) and sirius red (fibrosis, tubular dilation) staining. Diabetes rats displayed reduced serum albumin levels, marked proteinuria, lower kidney reduced glutathione content, glomerular hypertrophy, glomerulosclerosis, mesangial expansion, tubular dilation and renal fibrosis. Cobalt chloride treatment normalised renal HIF-1α protein levels, reduced development of proteinuria and tubulo-interstitial fibrosis, but the glomerular morphological alterations such as glomerulosclerosis, mesangial expansion, increased glomerular diameter and tubular vacoulations were not abrogated in diabetic kidneys. Glomerular morphological abnormalities might precede the development of proteinuria and renal fibrosis in experimental model of type 1 diabetes. Pharmacological modulation of renal HIF-1α protein levels does not influence glomerular and tubular dilatory changes in diabetic kidney disease.
KeywordsGlomerular hypertrophy Mesangial expansion Hypoxia inducible factors Tubulointerstitial fibrosis Type 1 diabetes
Gaaminepreet Singh received Basic Science Research fellowship from University Grant Commission, New Delhi, India during Ph.D study.
GS designed research and conducted experiments. PK helped in analysing data and manuscript drafting. All authors read and approved the manuscript.
Compliance with ethical standards
The experimental procedures on rats were approved by institutional animal ethics committee of Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala (Punjab), India.
Conflict of interest
The authors declare that they have no conflicts of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of institutional animal ethics committee of Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala (Punjab), India.
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