Zinc protects renal function during cadmium intoxication in the rat.
This study investigates the effect in the rat of chronic CdCl2 intoxication (500 microg Cd2+/kg, daily i.p. injection for 5 days) on renal function and the changes in tight junction proteins claudin-2, claudin-3, and claudin-5 present in rat kidney. We also studied the effect of coadministration of ZnCl2 (500 microg Zn2+/kg) during chronic CdCl2 intoxication. Our results indicate that 1) most of the filtered Cd2+ is reabsorbed within the kidney; 2) chronic Cd2+ intoxication can induce a change in renal handling of ions without altering glomerular filtration rate; 3) a delayed nephropathy, showing Fanconi-like features, appears more than 5 days after the end of CdCl2 exposure; 4) epithelial integrity is altered by chronic Cd2+ intoxication affecting the expression and localization of claudin tight junction proteins; and 5) cotreatment with Zn2+ protects against the renal toxic effects of Cd2+, preventing altered claudin expression and inhibiting apoptosis. In conclusion, these results show that Cd2+ toxicity and cellular toxic mechanisms are complex, probably affecting both membrane transporters and tight junction proteins. Finally, Zn2+ supplementation may provide a basis for future treatments.
Jacquillet
G
G
UMR-CNRS 6548, Bâtiment Sciences Naturelles, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.
Barbier
O
O
Cougnon
M
M
Tauc
M
M
Namorado
M C
MC
Martin
D
D
Reyes
J L
JL
Poujeol
P
P
D000818:Animals; D017209:Apoptosis; D001835:Body Weight / Q000187:drug effects; D002105:Cadmium Poisoning / Q000378:metabolism / Q000503:physiopathology*; D062465:Claudin-3; D057167:Claudins; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007477:Ions / Q000097:blood; D007668:Kidney / Q000503:physiopathology*; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000378:metabolism; D014554:Urination / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D062465:Claudin-3; D057167:Claudins; C491874:Cldn2 protein, rat; C568124:Cldn3 protein, rat; D007477:Ions; D008565:Membrane Proteins; D015032:Zinc