Species differences in arsenic-mediated renal copper accumulation: a comparison between rats, mice and guinea pigs.
1. Administration of arsenite leads to an accumulation of copper in the rat kidney. Owing to the high retention of arsenic in the erythrocytes, however, the rat is considered to possess special toxicokinetics of arsenic and is therefore considered less comparable with other species in this respect. 2. Therefore, we compared the effect of dietary arsenite in mice and guinea pigs with that in rats. Each species was divided into four groups of animals according to the diets fed which contained increasing concentrations of sodium arsenite (NaAsO2; 0, 10, 30 and 60 mg As/kg of diet). Animals were killed after 1, 2 and 3 weeks. Tissues were sampled and analyzed for arsenic and other trace metals (Cu, Fe, Zn and Mn). 3. Compared to controls with copper levels of about 10 microg Cu/g wet wt. in the renal cortex, dietary administration of arsenite up to 60 mg As/kg of diet for 3 weeks to rats increased cortical levels to 65 microg Cu/g wet wt. An increase of renal copper levels similar to that in rats, was only observed in guinea pigs but not in mice. Renal copper accumulation in guinea pigs was time- and concentration-dependent as in rats. Feeding a diet with 60 mg As/kg for 3 weeks increased cortical copper levels from about 6 - 40 microg Cu/g wet wt. Renal copper levels in mice as well as other trace metal levels in guinea pigs and mice were not essentially altered by dietary arsenite. 4. The study shows that the renal copper-arsenic interaction is not restricted to the rat. Since in rats and guinea pigs, but not in mice, arsenic accumulated in the kidney rather similarly, a common mechanism is suggestive. As it was previously shown in rats that only inorganic arsenic is involved in this interaction, a rapid conversion of the inorganic form into methylated metabolites as in mice may diminish the extent of the renal copper accumulation whereas the lack of, or a less efficient, methylation as in guinea pigs or rats increases it.
Hunder
G
G
Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität, Nussbaumstrasse 26, D-80336 München, Germany.
Schaper
J
J
Ademuyiwa
O
O
Elsenhans
B
B
D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003300:Copper / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism*; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D003300:Copper; D001151:Arsenic