Combined Effect of Dietary Cadmium and Benzo(a)pyrene on Metallothionein Induction and Apoptosis in the Liver and Kidneys of Bank Voles

Bank voles free living in a contaminated environment have been shown to be more sensitive to cadmium (Cd) toxicity than the rodents exposed to Cd under laboratory conditions. The objective of this study was to find out whether benzo(a)pyrene (BaP), a common environmental co-contaminant, increases Cd toxicity through inhibition of metallothionein (MT) synthesis—a low molecular weight protein that is considered to be primary intracellular component of the protective mechanism. For 6 weeks, the female bank voles were provided with diet containing Cd [less than 0.1 μg/g (control) and 60 μg/g dry wt.] and BaP (0, 5, and 10 μg/g dry wt.) alone or in combination. At the end of exposure period, apoptosis and analyses of MT, Cd, and zinc (Zn) in the liver and kidneys were carried out. Dietary BaP 5 μg/g did not affect but BaP 10 μg/g potentiated rather than inhibited induction of hepatic and renal MT by Cd, and diminished Cd-induced apoptosis in both organs. The hepatic and renal Zn followed a pattern similar to that of MT, attaining the highest level in the Cd + BaP 10-μg/g group. These data indicate that dietary BaP attenuates rather than exacerbates Cd toxicity in bank voles, probably by potentiating MT synthesis and increasing Zn concentration in the liver and kidneys

Metabolism and toxicity of cadmium in humans and animals

Cadmium (Cd(II)) is one of the most important toxic chemicals due to its increasing level in the environment as a result of industrial and agricultural practices. Cd(II) has a very long biological half-life (10-30 years) in humans and its toxicity is dependent on the dose, route and duration of exposure. Cd(II) is absorbed from the gastro-intestinal tract primarily by utilizing transporters for essential elements such as iron and zinc, as well as calcium channels. In this review multiple mechanisms of Cd(II) toxicity are discussed, such as interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species, modulation of signal transduction and gene expression, inhibition of DNA repair and DNA methylation, and disruption of E-cadherin-mediated cell-cell adhesion. The role of Cd(II) in apoptosis is also discussed