Toxicological Sciences, Vol 48, 134-140, Copyright © 1999 by Society of Toxicology
MF Khan, X Wu, PJ Boor and GA Ansari
Our earlier studies with aniline suggested the involvement of oxidative
stress as an early toxic event in the spleen. In order to understand the
status and consequences of the damaging oxidative reactions, especially
during the progression of characteristic splenic lesions, time-dependent
subchronic studies were conducted in rats. Male Sprague- Dawley rats were
treated with 65 mg/kg/day aniline in the drinking water, while control rats
received drinking water only. The animals were euthanized after 1, 2, or 3
months of aniline exposure. Total iron content was remarkably greater in
the aniline-treated rats than in age- matched controls. There were
time-dependent increases in splenic lipid peroxidation of aniline-treated
rats. Malondialdehyde-protein adducts were quantitated by a competitive
ELISA and showed greater concentrations in the spleens of aniline-treated
rats, further substantiating our lipid peroxidation results. Protein
oxidation in the spleens of aniline-treated rats was also greater, with a
maximum increase of approximately 76% at 3 months. Western blot analysis
for oxidized proteins showed two distinct protein bands at approximately
114 kD and approximately 69 kD in both post-nuclear and mitochondrial
fractions of the spleens. Furthermore, densitometric analysis of the blot
showed increased band intensities of the oxidized proteins in both these
spleen fractions from aniline-treated rats, suggesting the susceptibility
of these proteins to aniline-induced oxidative stress. The most prominent
morphological changes in the spleens of aniline- treated rats included
thickening of the capsule, and capsular cells with nuclear prominence and
hyperchromia indicative of capsular hyperplasia. These capsular changes and
fibrosis of capsule, splenic trabeculae, and red pulp were noted at all
three time points after aniline exposure. Our studies thus suggest that
aniline-induced oxidative stress in the spleen is an ongoing event that
leads to oxidative modifications of biomolecules. Such oxidative
modifications, directly or indirectly, could contribute to the splenic
toxicity leading to deleterious consequences, including capsular
hyperplasia and fibrosis, as observed in this study, and possibly
tumorigenesis in chronic aniline exposure conditions.
ARTICLES
Oxidative modification of lipids and proteins in aniline-induced splenic toxicity
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609, USA. mfkhan@utmb.edu
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