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Effects of chronic exposure to cadmium on renal cytochrome P450-dependent monooxygenase system in rats

  • Inorganic Compounds
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Abstract

The aim of this study was to evaluate the effects of chronic exposure to cadmium (Cd) on the renal cytochrome P450-dependent monooxygenase system. For this purpose, male Wistar rats were intoxicated with Cd administered in drinking water at a concentration of 5 or 50 mg Cd/l for 6, 12 and 24 weeks. Concentrations of cytochrome P450 and cytochrome b5 as well as activities of NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase were determined in the kidney microsomal fraction. Protein content of CYP1A1, CYP2E1 and CYP3A1 cytochrome P450 isoforms was evaluated as well. In the rats exposed to 5 mg Cd/l, the concentration of cytochrome P450 decreased (by 41%) after 24 weeks of the experiment. The activity of NADPH-cytochrome P450 reductase decreased (by 24%) after 6 and 12 weeks, whereas after 24 weeks it remained unchanged, compared with the control group. Moreover, a decrease in the concentration of cytochrome b5 (by 25, 15 and 26% at 6, 12 and 24 weeks, respectively) and the activity of its NADH reductase (by 26 and 31% at 6 and 24 weeks, respectively) was noted in these animals. At the exposure to 50 mg Cd/l, the concentrations of cytochrome P450 and cytochrome b5 and the activities of their corresponding reductases were decreased at each time-point. Western blot analysis revealed that all isoforms of cytochrome P450 studied were affected by Cd and the effect was dependent on the level and the duration of exposure. The results of this study indicate that chronic exposure to Cd in a dose- and time-dependent manner affects the kidney cytochrome P450-dependent monooxygenase system by decreasing the concentrations of cytochrome P450 and cytochrome b5 and inhibiting the activities of their corresponding reductases. The effect of Cd on the cytochrome P450 content is associated with its ability to stimulate or inhibit of various P450 isoforms. A very important finding of this study is that Cd affects the kidney cytochrome P450-dependent monooxygenase system at relatively low exposure and low kidney Cd accumulation (2.40±0.15 μg/g). As the experimental model used reflects human exposure to Cd, we conclude that Cd can affect the kidney cytochrome P450-dependent monooxygenase system in environmentally exposed humans. Previously we have reported disorders in the system in the liver of rats at the same levels of exposure as in this study. Thus, we hypothesize that the metabolism and detoxification of many substances, including xenobiotics, may be seriously affected in Cd-exposed subjects.

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Acknowledgements

The present study was supported by Grant No. 4PO5D 012 19 from the Committee for Scientific Research (KBN, Poland).

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Authors and Affiliations

  1. Department of Histology and Embryology, Medical University of Silesia, Medyków 20, 40-752, Katowice-Ligota, Poland

    Andrzej Plewka, Danuta Plewka, Grażyna Nowaczyk & Marcin Kamiński

  2. Department of Toxicology, Medical University of Białystok, Mickiewicza 2C, 15-222, Białystok, Poland

    Małgorzata M. Brzóska & Janina Moniuszko-Jakoniuk

Authors
  1. Andrzej Plewka
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  2. Danuta Plewka
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  3. Grażyna Nowaczyk
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  4. Małgorzata M. Brzóska
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  5. Marcin Kamiński
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  6. Janina Moniuszko-Jakoniuk
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Correspondence to Andrzej Plewka.

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Part of this work was presented at the EUROTOX 2001, Istanbul, Turkey, 2001

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Plewka, A., Plewka, D., Nowaczyk, G. et al. Effects of chronic exposure to cadmium on renal cytochrome P450-dependent monooxygenase system in rats. Arch Toxicol 78, 194–200 (2004). https://doi.org/10.1007/s00204-003-0529-9

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  • DOI: https://doi.org/10.1007/s00204-003-0529-9

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