Dietary Choline Deprivation Exacerbates Kidney Injury in Streptozotocin-Induced Diabetes in Adult Rats

<b>Background</b>: Choline (Ch) deprivation causes kidney injury and dysfunction, and diabetic nephropathy is also known to be a complication of diabetes; thus, this interplay could potentially aggravate diabetic kidney disease. <b>Aim</b>: This study aims to examine the effe...

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Main Authors: Ahmed W. Al-Humadi, Carel W. le Roux, Neil G. Docherty, Werd Al-Najim, Martin Tze Wah Kueh, Andreas C. Lazaris, Charis Liapi
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Diabetology
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Online Access:https://www.mdpi.com/2673-4540/6/1/8
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author Ahmed W. Al-Humadi
Carel W. le Roux
Neil G. Docherty
Werd Al-Najim
Martin Tze Wah Kueh
Andreas C. Lazaris
Charis Liapi
author_facet Ahmed W. Al-Humadi
Carel W. le Roux
Neil G. Docherty
Werd Al-Najim
Martin Tze Wah Kueh
Andreas C. Lazaris
Charis Liapi
author_sort Ahmed W. Al-Humadi
collection DOAJ
description <b>Background</b>: Choline (Ch) deprivation causes kidney injury and dysfunction, and diabetic nephropathy is also known to be a complication of diabetes; thus, this interplay could potentially aggravate diabetic kidney disease. <b>Aim</b>: This study aims to examine the effect of Ch-deprivation on the severity of kidney injury in streptozotocin (STZ)-induced diabetic rats. <b>Methods</b>: Twenty-four adult male Wistar rats were divided into four groups: control (C), nondiabetic Ch-deprived (CD), diabetic (DM), and diabetic Ch-deprived (DM + CD). Diabetes was induced by the intraperitoneal administration of 50 mg/kg body weight STZ; Ch-deprivation was induced through a choline-deficient diet. Rats were euthanized at week 5 of the study. Biochemical tests, renal histopathology, immunohistochemistry of the kidney injury molecule-1 (KIM-1), and vascular endothelial growth factor-A (VEGF-A) expression were assessed. <b>Results</b>: DM + CD and DM groups demonstrated significant increases in glucose levels and in the homeostasis model of insulin resistance (HOMA IR). Creatinine and blood urea nitrogen levels significantly increased in the DM + CD group compared to the control, and homocysteine levels were higher in the CD group. Kidney histopathology revealed that renal tubular necrosis, mesangial matrix expansion, and renal fibrosis substantially increased in the DM + CD group compared to all other groups, and KIM-1 and VEGF-A expressions were most pronounced in the DM + CD and DM groups, respectively. <b>Conclusions</b>: Ch deprivation affected kidney function and structure in STZ-induced diabetic rats. Choline deficiency and diabetes seem to have a synergistic effect, as evidenced by kidney biochemistry, histopathology, and immunohistochemistry. These findings could highlight the important role of choline in therapeutic strategies for the treatment and, potentially, prevention of chronic diabetic kidney disease.
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spelling doaj-art-8cc55104794d47bf9d67ce7a1fd20a532025-01-24T13:28:46ZengMDPI AGDiabetology2673-45402025-01-0161810.3390/diabetology6010008Dietary Choline Deprivation Exacerbates Kidney Injury in Streptozotocin-Induced Diabetes in Adult RatsAhmed W. Al-Humadi0Carel W. le Roux1Neil G. Docherty2Werd Al-Najim3Martin Tze Wah Kueh4Andreas C. Lazaris5Charis Liapi6Diabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, D04 V1W8 Dublin, IrelandDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, D04 V1W8 Dublin, IrelandDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, D04 V1W8 Dublin, IrelandDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, D04 V1W8 Dublin, IrelandRoyal College of Surgeons in Ireland, University College Dublin Malaysia Campus, George Town 10450, Malaysia1st Department of Pathology, Medical School, University of Athens, 75 Mikras Asias, Goudi, 11527 Athens, GreeceDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland<b>Background</b>: Choline (Ch) deprivation causes kidney injury and dysfunction, and diabetic nephropathy is also known to be a complication of diabetes; thus, this interplay could potentially aggravate diabetic kidney disease. <b>Aim</b>: This study aims to examine the effect of Ch-deprivation on the severity of kidney injury in streptozotocin (STZ)-induced diabetic rats. <b>Methods</b>: Twenty-four adult male Wistar rats were divided into four groups: control (C), nondiabetic Ch-deprived (CD), diabetic (DM), and diabetic Ch-deprived (DM + CD). Diabetes was induced by the intraperitoneal administration of 50 mg/kg body weight STZ; Ch-deprivation was induced through a choline-deficient diet. Rats were euthanized at week 5 of the study. Biochemical tests, renal histopathology, immunohistochemistry of the kidney injury molecule-1 (KIM-1), and vascular endothelial growth factor-A (VEGF-A) expression were assessed. <b>Results</b>: DM + CD and DM groups demonstrated significant increases in glucose levels and in the homeostasis model of insulin resistance (HOMA IR). Creatinine and blood urea nitrogen levels significantly increased in the DM + CD group compared to the control, and homocysteine levels were higher in the CD group. Kidney histopathology revealed that renal tubular necrosis, mesangial matrix expansion, and renal fibrosis substantially increased in the DM + CD group compared to all other groups, and KIM-1 and VEGF-A expressions were most pronounced in the DM + CD and DM groups, respectively. <b>Conclusions</b>: Ch deprivation affected kidney function and structure in STZ-induced diabetic rats. Choline deficiency and diabetes seem to have a synergistic effect, as evidenced by kidney biochemistry, histopathology, and immunohistochemistry. These findings could highlight the important role of choline in therapeutic strategies for the treatment and, potentially, prevention of chronic diabetic kidney disease.https://www.mdpi.com/2673-4540/6/1/8cholinecholine-deprivationchronic kidney diseasediabetes mellitusratsstreptozotocin
spellingShingle Ahmed W. Al-Humadi
Carel W. le Roux
Neil G. Docherty
Werd Al-Najim
Martin Tze Wah Kueh
Andreas C. Lazaris
Charis Liapi
Dietary Choline Deprivation Exacerbates Kidney Injury in Streptozotocin-Induced Diabetes in Adult Rats
Diabetology
choline
choline-deprivation
chronic kidney disease
diabetes mellitus
rats
streptozotocin
title Dietary Choline Deprivation Exacerbates Kidney Injury in Streptozotocin-Induced Diabetes in Adult Rats
title_full Dietary Choline Deprivation Exacerbates Kidney Injury in Streptozotocin-Induced Diabetes in Adult Rats
title_fullStr Dietary Choline Deprivation Exacerbates Kidney Injury in Streptozotocin-Induced Diabetes in Adult Rats
title_full_unstemmed Dietary Choline Deprivation Exacerbates Kidney Injury in Streptozotocin-Induced Diabetes in Adult Rats
title_short Dietary Choline Deprivation Exacerbates Kidney Injury in Streptozotocin-Induced Diabetes in Adult Rats
title_sort dietary choline deprivation exacerbates kidney injury in streptozotocin induced diabetes in adult rats
topic choline
choline-deprivation
chronic kidney disease
diabetes mellitus
rats
streptozotocin
url https://www.mdpi.com/2673-4540/6/1/8
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