Cadmium-induced excretion of urinary lipid metabolites, DNA damage, glutathione depletion, and hepatic lipid peroxidation in sprague-dawley rats
- 221 Downloads
Recent studies have described lipid peroxidation to be an early and sensitive consequence of cadmium exposure, and free radical scavengers and antioxidants have been reported to attenuate cadmium-induced toxicity. These observations suggest that cadmium produces reactive oxygen species that may mediate many of the untoward effects of cadmium. Therefore, the effects of cadmium (II) chloride on reactive oxygen species production were examined following a single oral exposure (0.50 LD50) by assessing hepatic mitochondrial and microsomal lipid peroxidation, glutathione content in the liver, excretion of urinary lipid metabolites, and the incidence of hepatic nuclear DNA damage. Increases in lipid peroxidation of 4.0- and 4.2-fold occurred in hepatic mitochondria and microsomes, respectively, 48 h after the oral administration of 44 mg cadmium (II) chloride/kg, while a 65% decrease in glutathione content was observed in the liver. The urinary excretion of malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT), and acetone (ACON) were determined at 0–96 h after Cd administration. Between 48 and 72 h posttreatment maximal excretion of the four urinary lipid metabolites was observed with increases of 2.2- to 3.6-fold in cadmium (II) chloride-treated rats. Increases in DNA single-strand breaks of 1.7-fold were observed 48 h after administration of cadmium. These results support the hypothesis that cadmium induces production of reactive oxygen species, which may contribute to the tissue-damaging effects of this metal ion.
Index EntriesCadmium female Sprague-Dawley rats lipid peroxidation DNA damage glutathione depletion formaldehyde malondialdehyde acetaldehyde acetone
- 9.J. A. Buege and S. D. Aust, Microsomal lipid peroxidation,Methods Enzymol. 51, 302–310 (1972).Google Scholar
- 12.M. A. Shara, P. H. Dickson, D. Bagchi, and S. J. Stohs, Excretion of formaldehyde, malondialdehyde, acetaldehyde and acetone in the urine of rats in response to 2,7,8-tetrachlorodibenzo-p-dioxin, paraquat, endrin and carbon tetrachloride,J. Chromatogr. 576, 221–233 (1992).PubMedCrossRefGoogle Scholar
- 16.D. W. Foster, Diabetes mellitus, inHarrison's Principles of Internal Medicine, E. Braunwald, K. J. Isselbacher, R. G. Petersdorf, J. D. Wilson, J. B. Martin, and A. S. Fauci, eds., McGraw-Hill, New York, pp. 1778–1796 (1987).Google Scholar