Effect of cadmium on membrane potential in isolated rat hepatocytes.
The effect of cadmium (Cd) on rat hepatocytes upon short term exposure was studied by focusing on the integrity of mitochondria and on the possible consequences of its disturbance, such as alterations in plasma membrane potential and loss of cell viability. Changes in the potential of mitochondrion and plasma membranes were monitored using [3H]triphenylmethylphosphonium (TPMP+) and [14C]SCN- probes, respectively. Isolated rat hepatocytes were exposed to increasing CdCl2 concentrations for short time periods (30-120 min). Cd measurement by atomic absorption showed that the cells efficiently accumulated Cd, as did mitochondria in situ. In CdCl2-treated cultures, it was observed that the release of TPMP+, which revealed a drop in the mitochondrial membrane potential, was time- and concentration-dependent, and that the first significant efflux was caused by a 30-min exposure to 89 microM CdCl2. No significant change in plasma membrane potential, as judged from the increase in the uptake of SCN-, was detected after 30 min, suggesting the greater precocity of the mitochondrial attack. Finally, the release of lactate dehydrogenase (LDH) occurred only after 2 h of exposure, reflecting ultimate stages of cell injury induced by Cd. These results suggest that Cd induces an alteration in mitochondrial function in hepatocytes which may lead to the loss of plasma membrane potential and cell viability. The study therefore adds further evidence of the role of mitochondria as primary targets in Cd-induced cytotoxicity.
Martel
J
J
Department of Chemistry, Université du Québec à Montreal, Montréal, Canada.
Marion
M
M
Denizeau
F
F
D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D019256:Cadmium Chloride; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D007202:Indicators and Reagents; D007425:Intracellular Membranes / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009861:Onium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D013054:Spectrophotometry, Atomic; D013861:Thiocyanates; D014320:Triphenylmethyl Compounds; D014634:Valinomycin / Q000494:pharmacology
D007202:Indicators and Reagents; D009861:Onium Compounds; D013861:Thiocyanates; D014320:Triphenylmethyl Compounds; D002104:Cadmium; C011561:triphenylmethylphosphonium; D014634:Valinomycin; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D007770:L-Lactate Dehydrogenase; D019256:Cadmium Chloride