Contribution of nitrosobenzene to splenic toxicity of aniline.
To elucidate the mechanism(s) of splenic toxicity of aniline, studies were conducted with nitrosobenzene (NB), an N-oxidized metabolite of aniline. Male Sprague-Dawley rats were given 0.025, 0.05, 0.1, or 0.2 mmol/kg/d of NB in 0.5 ml of 0.25% agar by gavage for 4 d; control rats received the vehicle only. Animals were euthanized at 24 h following the last dose. NB treatment resulted in decreased erythrocyte counts, whereas methemoglobin content increased at 0.1- and 0.2-mmol/kg doses. Spleen weight to body weight ratios were greater by 55 and 81% at O.1- and 0.2-mmol/kg NB doses, respectively. Total iron content in the spleens of NB-treated rats showed dose-dependent significant increases, and the nonheme iron followed a similar pattern. Splenic lipid peroxidation showed a dose-dependent response and was greater by 19, 56, 74, and 85% at the 4 doses, respectively. Malondialdehyde (MDA)-protein adducts, as quantitated by a competitive enzyme-linked immunosorbent assay (ELISA), were markedly greater in all the NB-treated groups, with the highest increase of 248% at 0.2 mmol/kg. Furthermore, NB exposure also resulted in greater protein oxidation (carbonyl content) in the spleens at 0.1- and 0.2-mmol/kg doses. These results suggest that NB is a splenotoxin and therefore can contribute to the splenic toxicity of aniline. Results of this study further support our earlier findings that oxidative stress is a potential mechanism in the splenotoxicity of aniline.
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609, USA. mfkhan@utmb.edu
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D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004906:Erythrocyte Count / Q000187:drug effects; D007501:Iron / Q000032:analysis; D007958:Leukocyte Count / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000737:chemistry; D008706:Methemoglobin / Q000032:analysis; D009603:Nitroso Compounds / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D011506:Proteins / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology
D000814:Aniline Compounds; D002273:Carcinogens; D009603:Nitroso Compounds; D011506:Proteins; D008315:Malondialdehyde; D008706:Methemoglobin; D007501:Iron; C023650:aniline; C012456:nitrosobenzene