Evidence Suggesting a Role of Iron in a Mouse Model of Nephrogenic Systemic Fibrosis

The study investigated the role of iron in nephrogenic systemic fibrosis using a mouse model with chronic kidney disease. Mice injected with the gadolinium-based contrast agent Omniscan developed skin changes and dermal fibrosis, characterized by increased skin thickness and tissue iron accumulation. The addition of the iron chelator deferiprone significantly reduced skin thickness and dermal fibrosis, and prevented the infiltration of ferroportin-expressing cells. In vitro, deferiprone inhibited the release of catalytic iron and the differentiation of mononuclear cells into ferroportin-expressing cells. These findings suggested that iron played a crucial role in the toxicity of gadolinium chelates and the development of nephrogenic systemic fibrosis.