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 language | English (US) |
|---|---|
| Pages (from-to) | 95-102 |
| Number of pages | 8 |
| Journal | Toxicology |
| Volume | 194 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Dec 15 2003 |
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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 journal › Article
}
TY - JOUR
T1 - Nitrotyrosine formation in splenic toxicity of aniline
AU - Khan, M
AU - Wu, Xiaohong
AU - Kaphalia, Bhupendra
AU - Boor, Paul J.
AU - Ansari, Ghulam
PY - 2003/12/15
Y1 - 2003/12/15
N2 - 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.
AB - 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.
KW - Aniline
KW - Immunohistochemistry
KW - iNOS
KW - Nitrotyrosine
KW - Oxidative stress
KW - Spleen
UR - http://www.scopus.com/inward/record.url?scp=0242578364&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242578364&partnerID=8YFLogxK
U2 - 10.1016/j.tox.2003.08.008
DO - 10.1016/j.tox.2003.08.008
M3 - Article
C2 - 14636699
AN - SCOPUS:0242578364
VL - 194
SP - 95
EP - 102
JO - Toxicology
JF - Toxicology
SN - 0300-483X
IS - 1-2
ER -