title: Evaluation of novel biomarkers of nephrotoxicity in two strains of rat treated with Cisplatin.
abstract: Cisplatin is an anticancer agent that induces renal proximal tubule lesions in many species. Studies were conducted in Sprague-Dawley and Han-Wistar rats to evaluate the utility of novel preclinical biomarkers of nephrotoxicity for renal lesions caused by this compound. Groups of 10 males of each strain were given a single intraperitoneal injection of 0.3, 1, or 3 mg/kg cisplatin and were sacrificed on days 2, 3, and 5. The novel biomarkers α-glutathione-S-transferase (α-GST) (for proximal tubular injury), μ-glutathione-S-transferase (μ-GST) (for distal tubular injury), clusterin (for general kidney injury), and renal papillary antigen-1 (RPA-1) (for collecting duct injury) were measured in urine by enzyme immunoassay. Histologically, degeneration and necrosis of the S3 segment of the renal proximal tubule were observed on day 2 (Han-Wistar) and days 3 and 5 (both strains) at 1 and 3 mg/kg. Results showed that in both strains of rats, urinary α-GST and clusterin can be detected in urine soon after injury, are more sensitive than BUN and serum creatinine, and therefore are usable as noninvasive biomarkers of proximal tubule injury. Changes in both μ-GST or RPA-1 were considered to represent secondary minor effects of proximal tubular injury on distal segments of the nephron.
authors: sanofi-aventis R&D, Paris, France.
authors: Jean-Charles
authors: JC
authors: Gautier
authors: Björn
authors: B
authors: Riefke
authors: Jakob
authors: J
authors: Walter
authors: Petra
authors: P
authors: Kurth
authors: Lou
authors: L
authors: Mylecraine
authors: Valérie
authors: V
authors: Guilpin
authors: Norman
authors: N
authors: Barlow
authors: Thierry
authors: T
authors: Gury
authors: David
authors: D
authors: Hoffman
authors: Daniela
authors: D
authors: Ennulat
authors: Kerstin
authors: K
authors: Schuster
authors: Ernie
authors: E
authors: Harpur
authors: Syril
authors: S
authors: Pettit
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism*; D002945:Cisplatin / Q000633:toxicity*; D051152:Clusterin / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D051152:Clusterin; D005982:Glutathione Transferase; D002945:Cisplatin