TY - JOUR
T1 - Contribution of nitrosobenzene to splenic toxicity of aniline
AU - Khan, M. Firoze
AU - Wu, X.
AU - Ansari, G. A.S.
PY - 2000
Y1 - 2000
N2 - 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 0.1- and 0.2-mmol/kg NB doses, respectively. Total iron contentin 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 acompetitive 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.
AB - 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 0.1- and 0.2-mmol/kg NB doses, respectively. Total iron contentin 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 acompetitive 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.
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U2 - 10.1080/00984100050027815
DO - 10.1080/00984100050027815
M3 - Article
C2 - 10914691
AN - SCOPUS:0034705383
VL - 60
SP - 263
EP - 273
JO - Journal of Toxicology and Environmental Health - Part A: Current Issues
JF - Journal of Toxicology and Environmental Health - Part A: Current Issues
SN - 1528-7394
IS - 4
ER -