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

Abstract

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.

Cell size and cancer: a new solution to Peto's paradox?

“…; Salińska et al. ). Although epidemiological, cell culture, and animal experimental studies have shown an increased cancer incidence associated with heavy metals intoxication (Sunderman ; Trott et al.…”

“…Influence of toxins, heavy metals, and other mutagenic factors on cellular DNA is considered a main cause of tumor development (Voth and Ballard 2005;Khlifi and Hamza-Chaffai 2010;Włostowski et al 2010). Chronic exposure to any of these produces damage primarily to the metabolically active tissues (e.g., liver, kidneys, and intestines), including cellular degeneration and apoptosis, DNA mutations, interstitial inflammation, and whole organ dysfunction (e.g., Maciak et al 2011b;Sali nska et al 2012). Although epidemiological, cell culture, and animal experimental studies have shown an increased cancer incidence associated with heavy metals intoxication (Sunderman 1984;Trott et al 1995;Oller et al 1997;Salnikow and Zhitkovich 2008), the mechanisms of carcinogenesis remain poorly understood.…”

The Alchemist’s Approach to Metal Poisoning: Transforming the Metal Burden

“…As an illustration of this, MT null mice are more sensitive to Cd toxicity, including nephrotoxicity, indicating that MT-metal complexes are protective of renal function. Induction of MT by means other than metals, such as with polycyclic aromatic hydrocarbons, also protects against the effects of Cd, at least in the kidney and liver of bank voles [22]. MT, when bound with metals, especially when those metals are toxic (e.g., Cd, Hg, Pb) is more resistant to degradation in the lysosome and more likely to be excreted by the kidney in a nephrotoxic form [21].…”

“…For example, type I diabetics were administered 30 mg/day of Zn with no adverse effects on Cu status and an improvement in indicators of oxidative stress [39]. Nephrotoxicity would be a concern, however, the protection of induced MT on the kidney [22], and the antioxidant effects of vitamin E and Zn [23,25], as well as a slow mobilization of metals should mitigate this risk. Renal compromised patients would need additional supervision.…”

The Effects of Lead and Selenium on Melanoma Induction

“…The consequences of exposures to lead, cadmium (Cd), and mercury and the consequent pathological changes in the liver, kidney and bone are well documented. [2][3][4][5][6][7][8][9][10] Moreover, thorium (Th), cadmium, lead, chromium (Cr), nickel (Ni), and beryllium (Be) are heavy metals with confirmed carcinogenic effects in animals and humans.11-15 Thus, there is an increasing evidence that the exposure to heavy metals could be associated with the occurrence of lung, liver, bladder, kidney, colon and skin cancer. 15 One of the most widely used heavy metals is lead.…”