Comparative Hepatotoxicity of Inhaled Cadmium Chloride and Cadmium Oxide

Abstract

The toxicity of inhaled aerosols of cadmium chloride (CdCl₂) and cadmium oxide (CdO) on hepatic biochemical function was compared. Male rats were exposed for 2 hours to concentrations of 0.45 and 4.5 mg Cd/m³. Serum and liver enzymes and histological changes were studied immediately and 72 hours after exposure. Exposure to 4.5 mg/m³ CdCl₂ and CdO resulted in an increase in liver Cd content. This deposition was not observed at the lower concentrations. Following exposure to 4.5 mg/m³ CdCl₂, decreases in body and liver weight, as well as decreased activities of glutathione (GSH)-reductase, GSH-peroxidase, and glucose-6-phosphate dehydrogenase (G-6-PDH) were observed. Increases in serum bilirubin and activities of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase were evident 72 hours after exposure. Exposure to 4.5 mg/m³ CdO caused decreased activities of GSH-reductase and peroxidase, G-6-PDH, and an increased activity of serum alkaline phosphatase and lactate dehydrogenase. Exposure to 0.45 mg/m³ CdCl₂, produced more hepatic effects than did a similar exposure to CdO. This differential response between inhalation of CdCl₂ and CdO was probably due to a rapid clearance of CdCl₂ or Cd²⁺ ions from the lung and transport to the liver via the systemic blood circulation.

References

1. Niewoehner, D.E. , and Hoidal, J.R. (1982). Lung fibrosis and emphysema: Divergent responses to a common injury? Science 217, 359–360.

2. Hammond, P.B. , and Beliles, L.P. (1980). Metals. In: Casarett and Doull's Toxicology. The Basic Science of Poisons. J. Doull , C.D. Klaassen , and M.O. Amdur , eds. New York: Macmillan, p. 432.

3. Oberdorster, G. , Baumert, H.P. , Hochrainer, D. , and Stoeber, W. (1979). The clearance of cadmium aerosols after inhalation exposure. Am. Ind. Hyg. Assoc. J. 40, 443–450.

4. Tandon, S.K. , and Asokan, P. (1981). Distribution of intratracheally administered cadmium in rats. Acta. Pharmacol. Toxicol. 49, 381–383.

5. Hadley, J.G. , Conklin, A.W. , and Sanders, C.L. (1980). Rapid solubilization and translocation of 109CdO following pulmonary deposition. Toxicol. Appl. Pharmacol. 54, 156–160.

6. Schnell, R.C. (1978). Cadmium-induced alteration of drug action. Fed. Proc. 37, 28–34.

7. Krasny, H.C. , and Holbrook, D.J. , Jr. (1977). Effects of cadmium on microsomal hemoproteins and heme oxygenase in rat liver. Molec. Pharmacol. 13, 759–765.

8. Hadley, W.M. , Miya, T.S. , and Bousquet, W.F. (1974). Cadmium inhibition of hepatic drug metabolism in the rat. Toxicol. Appl. Pharmacol. 28, 284–291.

9. Means, J.R. , Carlson, G.P. , and Schnell, R.C. (1979). Studies on the mechanism of cadmium-induced inhibition of the hepatic microsomal monooxygenase of the male rat. Toxicol. Appl. Pharmacol. 48, 293–304.

10.

10. Unger, M. , and Clausen, J. (1973). Liver cytochrome P-450 activity after intraperitoneal administration of cadmium salts in the mouse. Environ. Physiol. Biochem. 3, 236–242.

11.

11. Schnell, R.C. , Means, J.R. , Roberts, S.A. , and Pence, D.H. (1979). Studies on cadmium-induced inhibition of hepatic microsomal drug biotransformation in the rat. Environ. Health Perspect. 28, 273–279.

12.

12. Adkins, B. , Luginbuhl, G. , and Gardner, D.E. (1980). Acute exposure of laboratory mice to manganese oxide. Am. Ind. Hyg. Assoc. J. 41, 494–500.

13.

13. Gardner, D.E. , Miller, F.J. , Illing, J.W. , and Kirtz, J.M. (1977). Alterations in bacterial defense mechanisms of the lung induced by inhalation of cadmium. Bull. Eur. Physiopathol. Resp. 13, 157–174.

14.

14. Prohaska, J.R. , and Ganther, H.E. (1976). Selenium and glutathione peroxidase in developing rat brain. J. Neurochem. 27, 1379–1387.

15.

15. Carlsberg, I. , and Mannervik, B. (1975). Purification and characterization of the flavoenzyme glutathione reductase from rat liver. Biol. Chem. 250, 5475–5480.

16.

16. Habig, W.H. , Pabst, M.J. , and Jakoby, W.B. (1974). Glutathione-S-transferases. The first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249, 7130–7139.

17.

17. Mustafa, M.G. , Hacker, A.D. , Ospital, J.J. , Hussain, M.Z. , and Lee, S.D. (1977). Biochemical effects of environmental oxidant pollutants in animal lungs. In: Biochemical Effects of Environmental Pollutants. S.D. Lee , ed. Ann Arbor, MI: Ann Arbor Science Publishers, pp. 59–96.

18.

18. Jaskot, R.H. , Charlet, E.G. , Grose, E.C. , and Grady, M.A. (1983). An automated analysis of glutathione peroxidase, S-transferase, and reductase activity in animal tissue. J. Analyt. Toxicol. 7, 86–88.

19.

19. Dayton, C.M. , and Schafer, W.D. (1973). Extended tables of t and Chi-square for Bonferroni tests of unequal error allocation. J. Am. Stat. Assoc. 68, 78–83.

20.

20. Dudley, R.E. , Svoboda, D.J. , and Klaassen, C.D. (1982). Acute exposure to cadmium causes severe liver injury in rats. Toxicol. Appl. Pharmacol. 65, 302–313.

21.

21. Vallee, B.L. , and Ulmer, D.D. (1972). Biochemical effects of mercury, cadmium and lead. Annu. Rev. Biochem. 41, 91–128.

22.

22. Reddy, C.C. , Scholz, R.W. , and Massaro, E.J. (1981). Cadmium, methylmercury, mercury, and lead inhibition of calf liver glutatione S-transferase exhibiting selenium-independent glutathione peroxidase activity. Toxicol. Appl. Pharmacol. 61, 460–468.

23.

23. Splittgerber, A.G. , and Tappel, A.L. (1979). Inhibition of glutathione peroxidase by cadmium and other metal ions. Arch. Biochem. Biophys. 197, 534–542.

24.

24. Cantarow, A. , and Trumper, M. (1975). Enzymes. In: Clinical Biochemistry. A.L. Latner , ed. Philadelphia: W.B. Saunders, Vol. 7, pp. 557, 566.

25.

25. Grose, E.C. , Graham, J.A. , and Dauterman, W.C. (1987). A comparative study of the effects of inhaled cadmium chloride and cadmium oxide: Pulmonary response. J. Toxicol. Environ. Health 21, 219–232.

26.

26. Post, C.T. , Squibb, K.S. , Fowler, B.A. , Gardner, D.E. , Illing, J. , and Hook, G.E.R. (1982). Production of low molecular weight cadmium-binding proteins in rabbit lung following exposure to cadmium chloride. Biochem. Pharmacol. 31, 2969–2975.

27.

27. Oberdorster, G. , and Morrow, P.E. (1983). Effects of inhaled cadmium oxide on cadmium transfer across epithelial and endothelial structures of the lung. In: Heavy Metals in the Environment. Edinburgh: CEP Consultants, pp. 718–721.

28.

28. Raabe, O.G. , McFarland, K.D. , and Parkington, B.K. (1979). Generation of respirable aerosols of power plant fly ash for inhalation studies with experimental animals. Environ. Sci. Tech. 13, 836–840.