title: Mechanistic study on aniline-induced erythrocyte toxicity.
abstract: Strategies for the use of bio-indicators in the prediction of environmental damage should include mechanistic research. This study involves the relationship between the chemical structure and hemotoxic markers of aniline and its halogenated analogs. Aniline-induced methemoglobinemia, loss of circulating blood cells, blood stability, glutathione depletion and membrane cytoskeletal changes were assessed following exposure to phenylhydroxylamine (PHA), para-fluoro-, para-bromo-, and para-iodo in male Sprague-Dawley rats. Methemoglobin was determined spectrophotometrically at 635 nm. Erythrocyte depletion was investigated by loss of radioactivity in chromium-labeled red blood cells in vivo. Membrane proteins were analyzed by SDS-PAGE using red blood ghost cells treated with various aniline analogs. Results showed dose- and time-dependent changes in the induction of methemoglobin of up to 78% with para-bromo PHA and 75% with para-iodo PHA compared to 3% to 5% in control. Treated animals lost up to three times more blood from circulation compared to control within 14 days after treatment. Erythrocytes were more stable in buffer solution than in para-iodo-treated cells. Depletion of reduced glutathione in PHA and para-iodo-PHA treated red cells was also observed. Analysis of red cell skeletal membrane treated with para-iodo-PHA showed that protein band 2.1 became broader and band 2.2 diminished completely in some treatments. Dose- and time-dependent changes suggested the use of hemotoxic endpoints as potential biomarkers for assessing chemical and drug safety.
authors.affiliation: Department of Natural Science and Mathematics, College of Sciences and Technology, Savannah State University, Savannah, Georgia, USA. singhh@savstate.edu
authors.forename: Harpal
authors.initials: H
authors.lastname: Singh
authors.forename: Elissa
authors.initials: E
authors.lastname: Purnell
authors.forename: Carion
authors.initials: C
authors.lastname: Smith
mesh_terms: D000743:Anemia, Hemolytic / Q000139:chemically induced; D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000814:Aniline Compounds; D008706:Methemoglobin; D005978:Glutathione