Phenylhydroxylamine: role in aniline-associated splenic oxidative stress and induction of subendocardial necrosis

Toxicological Sciences : an Official Journal of the Society of Toxicology
M F KhanPaul J Boor

Abstract

To elucidate the role of N-phenylhydroxylamine (PHA, N-hydroxylated metabolite of aniline) in the selective toxicity of aniline to the spleen, dose-dependent studies were conducted with PHA in rats. Male Sprague-Dawley rats were given four doses each (1 dose/day) of 0.025, 0.05, 0.1, or 0.2 mmol/kg PHA in 0.5 ml of aqueous agar (0.25%) by gavage. The control animals received an equal volume of vehicle only. The animals were euthanized 24 h following the last dose. PHA toxicity in the blood was evident from a dose-dependent increase of methemoglobin. The most affected organ was spleen, which appeared dark and enlarged (splenomegaly) and showed increased spleen-to-body weight ratios, which were 28, 40, 66, and 87% at PHA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg, respectively. Splenic lipid peroxidation (malondialdehyde content) was higher in all PHA-treated groups, whereas splenic protein oxidation (carbonyl content) increased in only the 0.05, 0.1, and 0.2 mmol/kg groups. The total iron content in the spleen also showed increases of 88, 135, 168, and 209% at PHA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg, respectively. These biochemical changes were accompanied by a dose-dependent vascular congestion in the spleen, a character...Continue Reading

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