Heme oxygenase‐1 induction in rat spleen following aniline exposure

Abstract

Splenic toxicity of aniline is characterized by vascular congestion, hyperplasia, fibrosis and development of a variety of sarcomas in rats. However, mechanisms underlying splenic toxicity are not well understood. Previously we observed that aniline exposure causes oxidative damage to the spleen. To further explore the involvement of oxidative mechanism in aniline toxicity, we evaluated the role of heme oxygenase‐1 (HO‐1), which catalyzes heme degradation leading to the formation of biliverdin, carbon monoxide and iron. Male SD rats were given 1 mmol/kg/day aniline in water by gavage for 1 or 7 days, while the controls received water only. HO‐1 quantitation by ELISA showed a 2.6 fold increase in spleens of rats treated with aniline for 7 days. These increases were supported by Western blot analysis (~2.5 fold increase in HO‐1 expression). No changes were observed in animals exposed for 1 day. Immunohistochemical analysis showed greater staining for HO‐1 in the red pulp areas of spleen from rats treated for 7 days. Increase in HO‐1 expression was associated with 1.9 fold increase in ferritin, 2.7 fold increase in total iron and, more importantly, a 3.5 fold increase in free iron in spleens of rats exposed for 7 days. It is evident from our data that increased HO‐1 expression and its association with iron accumulation could be an important pro‐oxidant mechanism leading to oxidative damage in the spleen. Supported by ES006476.