OXIDATIVE STRESS IN THE SPLENOTOXICITY OF ANILINE

Citation
Mf. Khan et al., OXIDATIVE STRESS IN THE SPLENOTOXICITY OF ANILINE, Fundamental and applied toxicology, 35(1), 1997, pp. 22-30
Citations number
38
Categorie Soggetti
Toxicology
ISSN journal
02720590
Volume
35
Issue
1
Year of publication
1997
Pages
22 - 30
Database
ISI
SICI code
0272-0590(1997)35:1<22:OSITSO>2.0.ZU;2-X
Abstract
Aniline-induced splenic toxicity is characterized by hemorrhage, capsu lar hyperplasia, fibrosis, and a variety of sarcomas in rats. Early bi ochemical events responsible for the observed effects are not known. T o understand the mechanism(s) of aniline-induced splenic toxicity, sin gle and multiple (four and seven) doses of 1 mmol/kg of aniline hydroc hloride(AH) were given in rats. Apart from changes in the hematologica l parameters, these studies demonstrated that AH could induce lipid pe roxidation and protein oxidation in the spleen, and significant increa ses were observed at four doses. Subsequently, a dose-response study o f AH was performed. Male SD rats were given four doses each (one dose/ day) of 0.25, 0.5, 1, and 2 mmol/kg of AH in water by gavage, while c ontrols received water only. Animals were euthanized 24 hr following t he last dose and tissues obtained. Spleen weight increased by 32 and 8 0% at 1 and 2 mmol/kg doses, respectively. Splenic lipid peroxidation showed dose-dependent increases of 24, 32, and 43% at 0.5, 1, and 2 mm ol/kg, respectively. Protein oxidation in the spleen, quantitated by c arbonyl content per milligram protein, shelved 10, 28, and 27% increas es at 0.5, 1, and 2 mmol/kg, respectively. Iron content in the spleen also showed dose-dependent increases of 72, 172, and 325% at 0.5, 1, a nd 2 mmol/kg, respectively. Dose-related histopathologic expansion of splenic red pulp was characterized by increasing vascular congestion ( most pronounced at 2 mmol/kg), increased red pulp cellularity, erythro phagocytosis, and cellular fragmentation at 1 and 2 mmol/kg; iron depo sition in red pulp also increased dramatically with dose. These studie s establish that aniline induces lipid peroxidation and protein oxidat ion in the spleen and suggest that oxidative stress plays a role in th e splenic toxicity of aniline. (C) 1997 Society of Toxicology.