Nitrotyrosine formation in splenic toxicity of aniline

M Khan, Xiaohong Wu, Bhupendra Kaphalia, Paul J. Boor, Ghulam Ansari

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Splenic toxicity of aniline is characterized by vascular congestion, hyperplasia, fibrosis and development of a variety of sarcomas in rats. However, the mechanisms of this selective splenic toxicity are not well understood. Previously we showed that aniline exposure causes oxidative damage to spleen. To further explore the oxidative mechanisms of aniline toxicity, we evaluated the contributions of nitric oxide. Nitric oxide reacts with superoxide anion to form peroxynitrite, a powerful oxidant that converts the tyrosine residues of proteins to nitrotyrosine (NT). Therefore, aim of this study was to establish the role of nitric oxide through the formation and localization of NT in the spleen of rats exposed to aniline. Male Sprague-Dawley (SD) rats were given 1mmol/kg per day aniline hydrochloride in water by gavage for 7 days, while the controls received water only. Immunohistochemical analysis for NT showed an intense staining in the red pulp areas of spleen from aniline-treated rats, localized in macrophages and sinusoidal cells. Occasionally mild NT immunostaining was also evident in the white pulp. Western blot analyses of the post-nuclear fraction of the spleens showed major nitrated proteins with molecular weights of 49, 30 and 18kDa. Immunohistochemical analysis of inducible nitric oxide synthase (iNOS) also showed increased expression in the red pulp of the spleens from aniline-treated rats; the cellular localization was similar to nitrated proteins. These studies suggest that oxidative stress in aniline toxicity also includes aberration in nitric oxide production leading to nitration of proteins. Functional consequences of such nitration will further elucidate the contribution of nitric oxide to the splenic toxicity of aniline.

Original languageEnglish (US)
Pages (from-to)95-102
Number of pages8
JournalToxicology
Volume194
Issue number1-2
DOIs
StatePublished - Dec 15 2003

Fingerprint

Toxicity
Rats
Nitric Oxide
Spleen
Pulp
Nitration
Proteins
3-nitrotyrosine
aniline
Peroxynitrous Acid
Oxidative stress
Water
Macrophages
Nitric Oxide Synthase Type II
Aberrations
Oxidants
Superoxides
Sarcoma
Hyperplasia
Blood Vessels

Keywords

  • Aniline
  • Immunohistochemistry
  • iNOS
  • Nitrotyrosine
  • Oxidative stress
  • Spleen

ASJC Scopus subject areas

  • Toxicology

Cite this

Nitrotyrosine formation in splenic toxicity of aniline. / Khan, M; Wu, Xiaohong; Kaphalia, Bhupendra; Boor, Paul J.; Ansari, Ghulam.

In: Toxicology, Vol. 194, No. 1-2, 15.12.2003, p. 95-102.

Research output: Contribution to journalArticle

Khan, M ; Wu, Xiaohong ; Kaphalia, Bhupendra ; Boor, Paul J. ; Ansari, Ghulam. / Nitrotyrosine formation in splenic toxicity of aniline. In: Toxicology. 2003 ; Vol. 194, No. 1-2. pp. 95-102.
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