Nephrotoxicity of hexachloro-1:3-butadiene in the male Hanover Wistar rat; correlation of minimal histopathological changes with biomarkers of renal injury

Swain, A., Turton, J.A., Scudamore, C., Maguire, D., Pereira, I., Freitas, S., Smyth, R., Munday, M., Stamp, C., Gandhi, M., Sondh, S., Ashall, H., Francis, I., Woodfine, J., Bowles, J. and York, M. (2012) Nephrotoxicity of hexachloro-1:3-butadiene in the male Hanover Wistar rat; correlation of minimal histopathological changes with biomarkers of renal injury. Journal of Applied Toxicology, 32 (6). pp. 417-428. 10.1002/jat.1727.

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DOI: 10.1002/jat.1727

Abstract

Hexachloro-1:3-butadiene (HCBD) causes damage specifically to the renal proximal tubule in rats. In the present study, injury to the nephron of male Hanover Wistar rats was characterized at 24h following dosing with HCBD in the range 5-90mgkg-1 to determine the most sensitive biomarkers of damage, that is, the biomarkers demonstrating significant changes at the lowest dose of HCBD, using a range of measurements in serum and urine, renal histopathology, and renal and hepatic gene expression. Histologically, kidney degeneration was noted at doses as low as 10mgkg-1 HCBD. Significant changes in the hepatic and renal gene expression categories of xenobiotic metabolism and oxidative stress were observed at 5mgkg-1 HCBD, and in the kidney alone, evidence of inflammation at 90mgkg-1 HCBD. Increases in the urinary excretion of α-glutathione S-transferase (α-GST) and kidney injury molecule-1 (KIM-1) were seen at 10mgkg-1 HCBD, and increases in urinary excretion of albumin and total protein were evident at 15mgkg-1 HCBD. The most sensitive, noninvasive biomarkers of HCBD-induced renal toxicity in Hanover Wistar rats were urinary α-GST and KIM-1. Urinary albumin measurement is also recommended as, although it is not the most sensitive biomarker, together with α-GST, albumin showed the largest relative increase of all the biomarkers investigated, and the protein is easily measured.

Item Type:Article
Uncontrolled Keywords:Hexachloro-1:3-butadiene; Rat; Renal injury; Toxicity; Toxicogenomics; Urinary biomarkers
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:3003
Journal or Publication Title:Journal of Applied Toxicology
Deposited By:Library Staff
Deposited On:22 Mar 2012 09:53
Last Modified:27 Apr 2012 09:14

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