Effects of cadmium-metallothionein on renal organic ion transport and lipid peroxidation in rats.
The effects of cadmium-metallothionein (Cd-MT) on organic ion uptake in renal cortical slices and lipid peroxidation in the kidney were studied in rats. For in vitro studies, slices were prepared from kidneys of control animals and incubated in buffer containing either cadmium chloride (CdCl2) or Cd-MT in equimolar Cd concentrations ranging from 5 x 10(-6) to 2 x 10(-4) M. Uptake into the slices of the organic anion p-aminohippuric acid (PAH) was found to be inhibited by both forms of Cd in a dose-dependent manner. Although this inhibition was slightly greater in the presence of Cd-MT, accumulation of Cd into the slices was approximately 12 times greater with CdCl2 than Cd-MT. Tetraethylammonium (TEA) uptake was less sensitive to the inhibitory effects of both CdCl2 and Cd-MT, although a dose-dependent inhibition did occur with higher Cd concentrations. To study the in vivo effects of Cd-MT on transport function and lipid peroxidation in the kidney, rats were injected with Cd-MT (0.3 mg Cd per kilogram body weight [bw]) and sacrificed at specific time intervals. Similar to the in vitro studies, PAH uptake into the renal cortical slices was markedly inhibited within 12 hours after Cd-MT injection whereas inhibition of TEA uptake was less and not observed until 48 hours after injection. Only a small increase (1.4-fold) in lipid peroxidation, as measured by generation of malondialdehyde (MDA), in the kidney was detected at four hours postinjection, and no further increase was observed at later time periods. The results suggest that Cd-MT affects the transport of organic anions and cations during its renal uptake but that lipid peroxidation may play only a minor role in Cd-MT-induced renal toxicity.
Suzuki
C A
CA
Department of Pharmacology, University of Western Ontario, London, Canada.
Cherian
M G
MG
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride; D066298:In Vitro Techniques; D007477:Ions; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008668:Metallothionein / Q000302:isolation & purification / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D010130:p-Aminohippuric Acid / Q000378:metabolism
D007477:Ions; C004203:cadmium-binding protein; D002104:Cadmium; D008315:Malondialdehyde; D008668:Metallothionein; D019256:Cadmium Chloride; D010130:p-Aminohippuric Acid