TY - JOUR
T1 - Up-regulation of heme oxygenase-1 in rat spleen after aniline exposure
AU - Wang, Jianling
AU - Ma, Huaxian
AU - Boor, Paul J.
AU - Ramanujam, V. M.Sadagopa
AU - Ansari, G. A.S.
AU - Khan, M. Firoze
N1 - Funding Information:
This work was supported by Grant ES06476 from the National Institute of Environmental Health Sciences (NIEHS) , NIH, and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NIH.
PY - 2010/2/15
Y1 - 2010/2/15
N2 - The splenic toxicity of aniline is characterized by vascular congestion, hyperplasia, fibrosis, and the development of a variety of sarcomas in rats. However, the underlying mechanisms by which aniline elicits splenotoxic response are not well understood. Previously we have shown that aniline exposure causes oxidative damage to the spleen. To further explore the oxidative mechanism of aniline toxicity, we evaluated the potential contribution of heme oxygenase-1 (HO-1), which catalyzes heme degradation and releases free iron. Male SD rats were given 1 mmol/kg/day aniline in water by gavage for 1, 4, or 7 days, and respective controls received water only. Aniline exposure led to significant increases in HO-1 mRNA expression in the spleen (2-and 2.4-fold at days 4 and 7, respectively) with corresponding increases in protein expression, as confirmed by ELISA and Western blot analysis. Furthermore, immunohistochemical assessment of spleen showed stronger immunostaining for HO-1 in the spleens of rats treated for 7 days, confined mainly to the red pulp areas. No changes were observed in mRNA and protein levels of HO-1 after 1 day exposure. The increase in HO-1 expression was associated with increases in total iron (2.4-and 2.7-fold), free iron (1.9-and 3.5-fold), and ferritin levels (1.9-and 2.1-fold) at 4 and 7 days of aniline exposure. Our data suggest that HO-1 up-regulation in aniline-induced splenic toxicity could be a contributing pro-oxidant mechanism, mediated through iron release, and leading to oxidative damage.
AB - The splenic toxicity of aniline is characterized by vascular congestion, hyperplasia, fibrosis, and the development of a variety of sarcomas in rats. However, the underlying mechanisms by which aniline elicits splenotoxic response are not well understood. Previously we have shown that aniline exposure causes oxidative damage to the spleen. To further explore the oxidative mechanism of aniline toxicity, we evaluated the potential contribution of heme oxygenase-1 (HO-1), which catalyzes heme degradation and releases free iron. Male SD rats were given 1 mmol/kg/day aniline in water by gavage for 1, 4, or 7 days, and respective controls received water only. Aniline exposure led to significant increases in HO-1 mRNA expression in the spleen (2-and 2.4-fold at days 4 and 7, respectively) with corresponding increases in protein expression, as confirmed by ELISA and Western blot analysis. Furthermore, immunohistochemical assessment of spleen showed stronger immunostaining for HO-1 in the spleens of rats treated for 7 days, confined mainly to the red pulp areas. No changes were observed in mRNA and protein levels of HO-1 after 1 day exposure. The increase in HO-1 expression was associated with increases in total iron (2.4-and 2.7-fold), free iron (1.9-and 3.5-fold), and ferritin levels (1.9-and 2.1-fold) at 4 and 7 days of aniline exposure. Our data suggest that HO-1 up-regulation in aniline-induced splenic toxicity could be a contributing pro-oxidant mechanism, mediated through iron release, and leading to oxidative damage.
KW - Aniline
KW - Ferritin
KW - Free radicals
KW - Heme oxygenase-1
KW - Iron
KW - Oxidative stress
KW - Spleen
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U2 - 10.1016/j.freeradbiomed.2009.11.027
DO - 10.1016/j.freeradbiomed.2009.11.027
M3 - Article
C2 - 19969074
AN - SCOPUS:74149094600
SN - 0891-5849
VL - 48
SP - 513
EP - 518
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 4
ER -