Oxidative stress in the splenotoxicity of aniline.
Aniline-induced splenic toxicity is characterized by hemorrhage, capsular hyperplasia, fibrosis, and a variety of sarcomas in rats. Early biochemical events responsible for the observed effects are not known. To understand the mechanism(s) of aniline-induced splenic toxicity, single and multiple (four and seven) doses of 1 mmol/kg of aniline hydrochloride(AH) were given in rats. Apart from changes in the hematological parameters, these studies demonstrated that AH could induce lipid peroxidation and protein oxidation in the spleen, and significant increases were observed at four doses. Subsequently, a dose-response study of 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 controls received water only. Animals were euthanized 24 hr following the last dose and tissues obtained. Spleen weight increased by 32 and 80% 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 mmol/kg, respectively. Protein oxidation in the spleen, quantitated by carbonyl content per milligram protein, showed 10, 28, and 27% increases 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, and 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, erythrophagocytosis, and cellular fragmentation at 1 and 2 mmol/kg; iron deposition in red pulp also increased dramatically with dose. These studies establish that aniline induces lipid peroxidation and protein oxidation in the spleen and suggest that oxidative stress plays a role in the splenic toxicity of aniline.
Khan
M F
MF
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609, USA.
Boor
P J
PJ
Gu
Y
Y
Alcock
N W
NW
Ansari
G A
GA
D000284:Administration, Oral; D000814:Aniline Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007501:Iron / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology
D000814:Aniline Compounds; D002273:Carcinogens; D007501:Iron; C023650:aniline