title: Effects of chronic exposure to low-level cadmium on renal tubular function and CYP2A6-mediated coumarin metabolism in healthy human subjects.
abstract: Relationships between cadmium (Cd) body burden, kidney function and coumarin metabolism were investigated using two groups of 197 and 200 healthy Thais with men and women in nearly equal numbers. A mean age of one group was 30.5 years and it was 39.3 years for the other group. Of 397, 20 subjects (5%) excreted urine Cd between 1.4 microg/g and 3.8 microg/g creatinine and these subjects faced 10-15% increase in the probability of having abnormal urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG-uria). The prevalence of NAG-uria varied with Cd body burden in a dose-dependent manner (chi2 = 22, P < 0.008). Also NAG-nuria was one of the three kidney effect markers tested that showed the greatest strength of correlation with urine Cd in both men and women (r = 0.48, P < 0.001). In addition, urine Cd excretion of men and women showed a positive correlation (r = 0.46 to 0.54, P < 0.001) with urine 7-hydroxycoumarin (7-OHC) excretion which was used as a marker of liver cytochrome P450 2A6 (CYP2A6) enzyme activity. Urinary Cd excretion accounted for 25% of the total variation in urine 7-OHC excretion (P < 0.001). These data suggest that Cd may increase the expression of CYP2A6 in liver, resulting in enhanced coumarin metabolism in subjects with high Cd body burden.
authors.affiliation: National Research Centre for Environmental Toxicology (EnTox), The University of Queensland, 39 Kessels Road, Coopers Plains, Brisbane, Qld. 4108, Australia. s.satarug@uq.edu.au
authors.forename: Soisungwan
authors.initials: S
authors.lastname: Satarug
authors.forename: Muneko
authors.initials: M
authors.lastname: Nishijo
authors.forename: Pailin
authors.initials: P
authors.lastname: Ujjin
authors.forename: Yuvaree
authors.initials: Y
authors.lastname: Vanavanitkun
authors.forename: Jason R
authors.initials: JR
authors.lastname: Baker
authors.forename: Michael R
authors.initials: MR
authors.lastname: Moore
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002104:Cadmium / Q000652:urine; D002105:Cadmium Poisoning / Q000201:enzymology* / Q000473:pathology* / Q000652:urine; D003374:Coumarins / Q000378:metabolism*; D065637:Cytochrome P-450 CYP2A6; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D014468:Umbelliferones / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D003374:Coumarins; D014468:Umbelliferones; D002104:Cadmium; C031477:7-hydroxycoumarin; C030123:coumarin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6