Up-regulation of heme oxygenase-1 in rat spleen after aniline exposure.
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.
Wang
Jianling
J
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0438, USA.
Ma
Huaxian
H
Boor
Paul J
PJ
Ramanujam
V M Sadagopa
VM
Ansari
G A S
GA
Khan
M Firoze
MF
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D015153:Blotting, Western; D002273:Carcinogens; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005293:Ferritins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D007150:Immunohistochemistry / Q000379:methods; D007501:Iron / Q000737:chemistry; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects*; D015854:Up-Regulation; D000097382:CD68 Molecule
D000814:Aniline Compounds; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002273:Carcinogens; D005293:Ferritins; D051547:Heme Oxygenase-1; D007501:Iron; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C023650:aniline