Toxicokinetics and biochemistry of cadmium with special emphasis on the role of metallothionein.

Cadmium is a toxic metal with extremely long biological half-time of 15-20 years in humans. It has for decades been known that cadmium exposure can cause a variety of adverse health effects, among which kidney dysfunction, lung diseases, disturbed calcium metabolism and bone effects are most prominent. Following long term exposure the kidney is the critical organ. Cadmium and its compounds give rise to lung cancer after inhalation and have been classified as human carcinogens. Metallothionein (MT) is a low-molecular -weight protein, 6500Da with high cysteine content and high metal affinity, which plays a major role in the kinetics and metabolism of cadmium. The balance between CdMT and non-bound Cd in renal tissue has been shown to be of crucial importance for expression of toxicity. The most well studied metallothioneins are metallothioneins I and II with their isoforms which are expressed in almost all mammalian tissues. Metallothionein III is expressed in brain and is rich in zinc. Since the blood-brain barrier keeps Cd outside the CNS, reported neurotoxic effects of Cd during development are likely to be secondary to an interference of Cd with Zn-metabolism and not a direct effect of Cd on brain cells. It is therefore of importance to investigate whether neurotoxicity induced by cadmium is related to mechanisms involving MT III in brain.