Effects of uranium depletion on 1α-hydroxylase in kidney of rats

Abstract

This study was designed to evaluate the effects of depleted uranium (DU) on 1α-hydroxylase in the kidney of rats and to delinerate the mechanism of damage to kidneys and bones by DU. Male Sprague-Dawley rats were surgically implanted with DU fragments at three dose levels (0.1 g, 0.2 g and 0.3 g). After 3, 6 or 12 months, the concentration of 1α,25(OH)₂D₃ in the kidney was measured by radioimmunoassay. The activity of 1α-hydroxylase was shown by the production of 1α,25(OH)₂D₃ after incubation. The results showed that the 1α-hydroxylase activity in the kidney was decreased after 3 months (27.2% at the medium dose DU group, p < 0.05; 33.4% at the high dose DU group, p < 0.01). In contrast, at 6 months and 12 months after implantation of DU, the activity of renal 1α-hydroxylase in DU-treated animals was not decreased significantly in comparison with the controls (p > 0.05). On the other hand, the activity of renal 1α-hydroxylase was decreased by 33.1% (p < 0.05) and 34.4% (p < 0.01) in blank control groups at 6 and 12 months, respectively, when compared with the blank control group at 3 months. In conclusion, this study showed that chronic DU exposure could induce renal damages and inhibit the synthesis of biologically active form of vitamin D, which may be the underlying mechanism of bone metabolic disorder caused by renal injury after DU exposure.

Keywords

depleted uranium 1α-hydroxylase kidney rat

References

Domingo JL Reproductive and developmental toxicity of natural and depleted uranium: a review. Reprod Toxicol 2001; 15: 603-609.

Craft E. , Abu-Qare A. , Flaherty M. , Garofolo M. , Rincavage H. , and Abou-Donia M. Depleted and natural uranium: chemistry and toxicological effects. J Toxicol Environ Health B Crit Rev. 2004; 7: 297-317.

Briner WE The evolution of depleted uranium as an environmental risk factor: lessons from other metals. Int J Environ Res Public Health 2006; 3: 129-135.

McClain DE , Benson KA , Dalton TK , et al. Health effects of embedded depleted uranium. Mil Med 2002; 167: 117-119.

Li R. , Su YP , Guo Y. , Xu H. , Lou SF , Ai GP , et al. Distribution of uranium in rats with implanted and removed depleted uranium fragments. Chin J Radiol Med Prot 2004; 24: 105-107.

McClain DE , Benson KA , Dalton TK , et al. Biological effects of embedded depleted uranium (DU): summary of armed forces radiobiology research institute research. Sci Total Environ 2001; 274: 115-118.

Tissandié E. , Guéguen Y. , Lobaccaro JM , Grandcolas L. , Voisin P. , Aigueperse J. , et al. In vivo effects of chronic contamination with depleted uranium on vitamin D3 metabolism in rat. Biochimica et Biophysica Acta 2007; 1770: 266-272.

Dusso AS , Brown AJ , and Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol 2005 ; 289: F8-F28.

Chen TC , Holick MF Vitamin D and prostate cancer prevention and treatment. Trends Endocrinol Metab 2003; 14: 423-430.

10.

van Driel M. , Koedam M. , Buurman CJ , Hewison M. , Chiba H. , Uitterlinden AG , et al. Evidence for auto/ paracrine actions of vitamin D in bone: 1α-hydroxylase expression and activity in human bone cells. FASEB J 2006; 20: 2417-2419.

11.

Bland R. , Markovic D. , Hills CE , Hughes SV , Chan SL , Squires PE , et al. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. J Steroid Biochem Mol Bio 2004; 89-90: 121-125.

12.

Tanaka Y. , Deluca HF Measurement of mammalian 25-hydroxyvitamin D3 24R- and 1 alpha- hydroxylase . Proc Natl Acad Sci U S A 1981; 78: 196-199.

13.

Horiuchi N. , Shinki T. , Suda S. , Takahashi N. , Yamada S. , Takayama H. , et al. A rapid and sensitive in vitro assay of 25-hydroxyvitamin D3-1 alpha-hydroxylase and 24-hydroxylase using rat kidney homogenates. Biochem Biophys Res 1984; 121: 174-180.

14.

Leggett RW , Pellmar TC The biokinetics of uranium migrating from embedded DU fragments. J Environ Radioact 2003; 64: 205-225.

15.

Ubios AM , Guglielmotti MB , Steimetz T. , and Cabrini RL Uranium inhibits bone formation in physiologic alveolar bone modeling and remodeling. Environ Res 1991; 54: 17-23.

16.

Kurttio P. , Komulainen H. , Leino A. , Salonen L. , Auvinen A. , and Saha H. Bone as a possible target of chemical toxicity of natural uranium in drinking water. Environ Health Perspect 2005; 113: 68-72.

17.

Kurttio P. , Auvinen A. , Salonen L. , Saha H. , Pekkanen J. , Makelainen I. , et al. Renal effects of uranium in drinking water. Environ Health Perspect 2002; 110: 337-342.

18.

Pellmar TC , Fuciarelli AF , Ejnik JW , et al. Distribution of uranium in Rats implanted with Depleted uranium pellets. Toxicol Sci 1999; 49: 29-39.

19.

Fukuda S. , Ikeda M. , Chiba M. , and Kaneko K. Clinical diagnostic indicators of renal and bone damage in rats intramuscularly injected with depleted uranium. Radiat Prot Dosimetry 2006; 118: 307-314.

20.

Abu-Qare AW , Abou-Donia MB Depleted uranium-the growing concern. J Appl Toxicol 2002; 22: 149-152.

21.

Zhu GY , Tan MG , Li YL , Xiang XQ , Hu HP , and Zhao SQ Accumulation and distribution of uranium in rats after implantation with depleted uranium fragments. J Radiat Res 2009; 50: 183-192.

22.

Zhu GY , Zhong WJ , Xiang XQ , Weng SF , and Pan XH Studies on the effect of bone metabolism and bone mineral injury in rats intramuscularly injected with depleted uranium. Fudan University J Med Sci 2007; 34: 821-827.

23.

Zhu GY , Xiang XQ , Chen X. , Wang LH , Hu HP , and Weng SF Renal dysfunction induced by long-term exposure to depleted uranium in rats . Arch Toxicol 2009; 83: 37-46.

24.

Tissandié E. , Guéguen Y. , Lobaccaro JM , Paquet F. , Aigueperse J. , and Souidi M. Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat. Arch Toxicol 2006; 80: 473-480.

25.

Wan B. , Fleming JT , Schultz TW , and Sayler GS In vitro immune toxicity of depleted uranium: effects on murine macrophages, CD4+ T Cells, and gene expression profiles. Environ Health Perspect 2006; 114: 85-91.