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.