Cytotoxicity of Cadmium and Characteristics of Its Transport in Cardiomyocytes
- 1 January 1999
- journal article
- Published by Elsevier BV in Toxicology and Applied Pharmacology
- Vol. 154 (1), 59-66
- https://doi.org/10.1006/taap.1998.8575
Abstract
Cadmium (Cd) is reported to produce cardiotoxicity at doses and exposure conditions that cause no effect in kidney or liver. The purpose of the present investigation was to examine the cytotoxicity of Cd to neonatal rat cardiomyocytes in primary culture and to elucidate the transport characteristics of Cd in these cells at a nontoxic concentration. Cd concentrations of 0.1 microM and higher that are well tolerated by hepatocytes and renal cortical epithelial cells were toxic to the cardiomyocyte. The plot of initial uptake rate of Cd at various concentrations was nonlinear suggesting that, in addition to simple diffusion, other processes may also be involved. These processes required metabolic energy as pretreatment with dinitrophenol or sodium fluoride inhibited 58 and 59% of the Cd uptake, respectively. The uptake of Cd was also affected by the incubation temperature and lowering the temperature from 37 to 4 degreesC reduced Cd uptake over 30 min by 61%. Cd uptake required interaction with membrane sulfhydryl groups; pretreatment with p-chloromercuribenzenesulfonic acid or mercuric chloride reduced Cd uptake by 46 and 58%, respectively. Cd utilized the transport pathways for calcium (Ca), zinc (Zn), and copper (Cu). Coincubation with 1.26 mM Ca competitively inhibited Cd uptake by 77%. In the presence of Ca, 30 microM Zn or Cu further inhibited Cd accumulation competitively by as much as 63 and 32%, respectively. Cd could enter the cardiomyocytes through Ca channels and Ca channel blocker, verapamil, inhibited up to 76% of Cd uptake. From the above results it can be concluded that Cd is highly toxic to the cardiomyocytes. A majority of Cd enters these cells through transport processes that exist for Ca, Zn, and Cu. The transport processes utilized by Cd are temperature sensitive and dependent on metabolic energy. Furthermore, these involve membrane sulfhydryl groups and include Ca channels.Keywords
This publication has 44 references indexed in Scilit:
- Myocyte injury by heminIn Vitro Cellular & Developmental Biology – Animal, 1993
- Cadmium and mercury accumulation in rat hepatocytes: Interactions with other metal ionsToxicology and Applied Pharmacology, 1992
- Differences in cadmium and mercury uptakes by hepatocytes: Role of calcium channelsToxicology and Applied Pharmacology, 1991
- Reduction of doxorubicin toxicity by methylene blue in cultured rat myocardial cellsBiochemical Pharmacology, 1989
- Cardiotoxicity of tricyclic antidepressants in primary cultures of rat myocardial cellsJournal of Toxicology and Environmental Health, 1984
- Acute exposure to cadmium causes severe liver injury in ratsToxicology and Applied Pharmacology, 1982
- The synthesis of metallothionein and cellular adaptation to metal toxicity in primary rat kidney epithelial cell culturesToxicology, 1980
- Establishment of contracting heart muscle cell culturesPublished by Springer Science and Business Media LLC ,1977
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- The Relationship of Cadmium in the Air to Cardiovascular Disease Death RatesJAMA, 1966