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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Swain, Aubrey Turton, John Scudamore, Cheryl Maguire, David Pereira, Ines Freitas, Sofia Smyth, Rosemary Munday, Michael Stamp, Clare Gandhi, Mitul Sondh, Surjit Ashall, Holly Francis, Ian Woodfine, Jennifer Bowles, John York, Malcolm |
| Description | Country affiliation: United kingdom Author Affiliation: Swain A ( Clinical Pathology, GlaxoSmithKline Research and Development, Park Road, Ware, Hertfordshire SG12 0DP, UK. aubrey.2.swain@gsk.com) |
| 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 24 h following dosing with HCBD in the range 5-90 mg kgâ »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 10 mg kgâ »¹ HCBD. Significant changes in the hepatic and renal gene expression categories of xenobiotic metabolism and oxidative stress were observed at 5 mg kgâ »¹ HCBD, and in the kidney alone, evidence of inflammation at 90 mg kgâ »¹ HCBD. Increases in the urinary excretion of -glutathione S-transferase ( -GST) and kidney injury molecule-1 (KIM-1) were seen at 10 mg kgâ »¹ HCBD, and increases in urinary excretion of albumin and total protein were evident at 15 mg kgâ »¹ HCBD. The most sensitive, noninvasive biomarkers of HCBD-induced renal toxicity in Hanover Wistar rats were urinary -GST and KIM-1. Urinary albumin measurement is also recommended as, although it is not the most sensitive biomarker, together with -GST, albumin showed the largest relative increase of all the biomarkers investigated, and the protein is easily measured. |
| File Format | HTM / HTML |
| ISSN | 0260437X |
| Issue Number | 6 |
| Volume Number | 32 |
| e-ISSN | 10991263 |
| Journal | Journal of Applied Toxicology |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2012-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Toxicology Biological Markers Butadienes Toxicity Fungicides, Industrial Kidney Diseases Chemically Induced Kidney Drug Effects Albuminuria Blood Diagnosis Urine Animals Apoptosis Cell Adhesion Molecules Genetics Dose-response Relationship, Drug Gene Expression Glutathione Transferase Injections, Intraperitoneal Isoenzymes Metabolism Pathology Kidney Tubules, Proximal Ultrastructure Liver Male Organ Size Oxidative Stress Rats Rats, Wistar Real-time Polymerase Chain Reaction Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Toxicology |
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