| Autor: |
AOYAGI, TEIICHIRO, HAYAKAWA, KUNIHIRO, MIYAJI, KEISUKE, ISHIKAWA, HIROMICHI, HATA, MAKOTO |
| Předmět: |
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| Zdroj: |
International Journal of Urology; Jun2003, Vol. 10 Issue 6, p332-338, 7p |
| Abstrakt: |
Abstract Background: Cadmium (Cd) is an important industrial pollutant, although its mechanism of toxicity has not been completely clarified. We studied Cd-induced subchronic nephrotoxicity and the cadmium evacuation system in rats and cultured human renal tubular cells. Methods: Male Sprague–Dawley rats were subcutaneously injected with 0.6 mg Cd/kg per day for periods of 3, 5 and 8 weeks. The concentration of Cd in urine, serum and kidneys was measured by atomic absorption spectrophotometry. Nephrotoxicity was evaluated based on the urinary concentration of β2 microglobulin (B2MG) and histopathological findings. Apoptotic cells were detected by nick-end labeling and DNA laddering, and were based on the level of caspase-3 activity. Cadmium-induced toxicity was also studied in cultured human renal tubular cells. Results: Nephrotoxicity was detected after 4 weeks of exposure to Cd, because Cd and B2MG appeared in urine. The tissue concentration of Cd increased linearly throughout the 8 weeks of exposure to Cd. The concentration of renal Cd did not change in the 3-week exposure group, but it decreased after withdrawal of Cd in the 5-week exposure group, suggesting an active Cd excretion mechanism started after the 4th week. The threshold Cd concentration for nephrotoxicity was 150 micrograms/gram wet tissue, at which concentration histological tubular damage started. Although the kidneys presented mainly necrosis, apoptosis was observed at weeks 4 and 5, before renal tubular necrosis occurred. In vitro DNA laddering was observed and peak caspase-3 activity was detected when the cells were exposed to the threshold concentration of Cd. Conclusion: Cadmium was effectively evacuated from the body by exfoliation of damaged renal tubular cells presenting focal tubular necrosis after the renal Cd concentration reached the threshold. Apoptosis may be involved in the regulation of Cd-induced nephrotoxicity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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