Ferrotoxicity and its amelioration by endogenous vitamin D in experimental acute kidney injury

Exp Biol Med (Maywood). 2020 Oct;245(16):1474-1489. doi: 10.1177/1535370220946271. Epub 2020 Aug 2.

Abstract

This work provides in-depth insights on catalytic iron-induced cytotoxicity and the resultant triggering of endogenous vitamin D synthesis in experimental acute kidney injury. Our results reveal significantly elevated levels of catalytic iron culminating in oxidant-mediated renal injury and a concomitant increase in 1,25-dihdyroxyvitamin D3 levels. Also, changes in other iron-related proteins including transferrin, ferritin, and hepcidin were observed both in the serum as well as in their mRNA expression. We consider all these findings vital since no connection between catalytic iron and vitamin D has been established so far. Furthermore, we believe that this work provides new and interesting results, with catalytic iron emerging as an important target in ameliorating renal cellular injury, possibly by timely administration of vitamin D. It also needs to be seen if these observations made in rats could be translated to humans by means of robust clinical trials.

Keywords: Catalytic iron; acute kidney injury; ferritin; hepcidin; oxidative stress; transferrin; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Acute Kidney Injury / pathology*
  • Animals
  • Biomarkers / metabolism
  • Catalysis
  • Gene Expression Regulation / drug effects
  • Iron / blood
  • Iron / toxicity*
  • Kidney / drug effects
  • Kidney / injuries
  • Kidney / pathology
  • Kidney / ultrastructure
  • Linear Models
  • Lipocalin-2 / metabolism
  • Male
  • Multivariate Analysis
  • Oxidative Stress / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Vitamin D / pharmacology*

Substances

  • Biomarkers
  • Lcn2 protein, rat
  • Lipocalin-2
  • RNA, Messenger
  • Vitamin D
  • Iron
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase