Iron deficiency anemia is a frequent complication in clinical conditions such as
chronic kidney disease, chronic
heart failure,
inflammatory bowel disease,
cancer, and excessive blood loss. Given the ability of
iron to catalyze redox reactions,
iron therapy can be associated with oxidative stress. The lung is uniquely susceptible to oxidative stress, and little is known about the effects of intravenous
iron treatment in this organ. This study characterized changes in markers of oxidative/nitrosative stress and
inflammation in the lung of non-
iron deficient, non-anemic rats treated with five weekly doses (40 mg
iron per kg
body weight) of low molecular weight
iron dextran (LMWID),
iron sucrose (IS),
ferric carboxymaltose (FCM),
ferumoxytol (FMX),
iron isomaltoside 1000 (IIM), or saline (control). Rats treated with LMWID, FMX, or IIM showed significant changes in most measures of oxidative/nitrosative stress,
inflammation, and
iron deposition compared to the saline-treated controls, with greatest changes in the LMWID treatment group. Increases in products of lipid peroxidation (
thiobarbituric acid reactive substances) and
protein nitrosation (
nitrotyrosine) were consistent with increases in the activity of
antioxidant enzymes (
catalase, Cu,Zn-SOD, GPx), decreases in antioxidative capacity (reduced:oxidized GSH ratio), increased levels of
transcription factors involved in the inflammatory pathway (NF-κB, HIF-1α), inflammatory
cytokines (TNF-α, IL-6), adhesion molecules (VCAM-1), markers of macrophage infiltration (ED-1), and
iron deposition (
Prussian blue,
ferritin). Since changes in measured parameters in FCM- or IS-treated rats were generally modest, the results suggest that FCM and IS have a low propensity to induce
lung inflammation. The relevance of these findings to clinical safety profiles of the tested intravenous
iron products requires further investigation.