Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model

Abstract

The physicochemical characteristics of intravenous iron complexes affect the extent of weakly-bound iron and thus the degree of oxidative stress. The new preparation iron isomaltoside 1000 (IIM) was compared to iron sucrose (IS) and a control group in terms of biochemistry, oxidative stress, inflammatory markers and iron deposition in the liver, heart and kidneys of healthy rats. Renal function was significantly impaired in the IIM group versus both IS and controls. Liver enzymes were also significantly higher in IIM-treated animals versus the other groups, indicative of hepatic injury. Systolic blood pressure was significantly lower following IIM administration compared to IS or control animals. Oxidative stress in the liver, heart and kidneys was greater in the IIM group, as indicated by significantly increased levels of malondialdehyde and antioxidant enzyme activity, accompanied by a significantly lower ratio of reduced to oxidized glutathione. Microscopy demonstrated more extensive positive staining for iron, and a smaller area of ferritin staining, in the liver, heart and kidneys of rats treated with IIM versus IS. Levels of the inflammatory markers TNF-α and IL6 were both significantly higher in the IIM group versus IS in all assessed tissues. These findings indicate that IIM has a less favorable safety profile than IS in healthy rats, adversely affecting iron deposition, oxidative stress and inflammatory responses, with impaired liver and renal function.

Key words

Intravenous iron - Iron dextran - Iron isomaltoside 1000 - Iron sucrose - Monofer - Oxidative stress

• References

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