Rapid plasma clearance of albumin-acrolein adduct in rats.
Thakore-KN; Gan-JC; Ansari-GA
Toxicol Lett 1994 Mar; 71(1):27-37
The plasma clearance of an albumin/acrolein (107028) adduct was studied in rats. Male Sprague-Dawley-rats were injected intravenously with 10 milligrams (mg) of native tritium (H3) labeled albumin or an albumin/acrolein adduct previously formed by reacting 5mg/ml albumin with 5 millimolar acrolein. Blood samples were collected at various times up to 33 hours post injection and assayed for H3 activity. The rate of clearance of albumin derived radioactivity from the animals was calculated from the data. The rats were killed after 33 hours and the blood, liver, kidneys, and spleen were collected and assayed for H3 activity. Other plasma, liver, kidney, and spleen samples were precipitated with trichloroacetic-acid (TCA) and the TCA soluble and insoluble fractions were analyzed for radioactivity. Albumin derived H3 activity was cleared significantly faster from the plasma of rats injected with the albumin/acrolein adduct than from those injected with native albumin, 68% versus 48% being cleared after 11 hours and 78% versus 68% being cleared after 33 hours. More than 90% of the plasma radioactivity was associated with the albumin and only 10% with the globulin fraction in all groups. The amounts of radioactivity in the whole liver, kidney, and spleen were higher in rats injected with the albumin/acrolein adduct than in those injected with native albumin; however, only the increase in the kidney was statistically significant. The TCA soluble fractions of kidney and liver tissues from rats injected with acrolein adducted albumin contained more radioactivity than those from rats injected with native albumin. The reverse was true for the TCA insoluble fraction of these tissues. The distribution of radioactivity between the TCA insoluble and soluble fractions of the spleen was similar for albumin/acrolein adduct and native albumin injected rats. The authors conclude that the albumin/acrolein adduct is cleared more rapidly from the circulation and degraded more rapidly by the liver and kidney than native albumin. The rate of plasma clearance of protein adducts must be considered when contemplating their use as exposure markers.
NIOSH-Publication; NIOSH-Grant; Grants-other; In-vivo-studies; Laboratory-animals; Aldehydes; Biokinetics; Chemical-binding; Protein-biochemistry; Blood-plasma; Tissue-distribution; Biochemical-indicators;
Author Keywords: Acrolein; Albumin adduct; Plasma clearance; Protein degradation
Human Biol Chem and Genetics University of Texas Med BR Dept of Human Biol Chem & Gene Galveston, Tex 77550-2774
Other Occupational Concerns; Grants-other
University of Texas Medical Branch, Galveston, Texas