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

Ahmed W. Al-Humadi, Carel W. le Roux, Neil G. Docherty, Werd Al-Najim, Martin Tze Wah Kueh, Andreas C. Lazaris, Charis Liapi

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Abstract

Background: 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. Aim: This study aims to examine the effect of Ch-deprivation on the severity of kidney injury in streptozotocin (STZ)-induced diabetic rats. Methods: 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. Results: 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. Conclusions: 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.
Original languageEnglish
Article number8
Pages (from-to)1-16
Number of pages16
JournalDiabetology
Volume6
Issue number1
Early online date20 Jan 2025
DOIs
Publication statusPublished (in print/issue) - 31 Jan 2025

Bibliographical note

Publisher Copyright:
© 2025 by the authors.

Data Access Statement

Data are available from the corresponding author only upon reasonable request.

Keywords

  • choline
  • choline-deprivation
  • chronic kidney disease
  • diabetes mellitus
  • rats
  • streptozotocin

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