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Parameters indicative of reversible proximal tubule injury in rats following administration of cisplatin
Author(s) -
McDuffie James Eric,
Sablad Marciano,
Sonee Manisha,
Ma Jing,
Varacolli Lynn,
Louden Calvert,
Guy Antonio,
Cuellar Jennifer
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1002.7
Subject(s) - lipocalin , osteopontin , clusterin , urinary system , cisplatin , medicine , creatinine , endocrinology , kidney , urology , dosing , acute kidney injury , cystatin c , vacuolization , nephrotoxicity , chemistry , apoptosis , chemotherapy , biochemistry
Qualification of selected renal biomarkers indicative of the progression of acute kidney injury (AKI) in rats has been reported, however, little is known about the reversibility of this condition. In a 28‐day reversibility study, rats (n=4/group) received either a single dose of cisplatin (1 mg/kg, i.p.) or vehicle. Sample collections and necropsy time points were 6‐ and 72‐hours, 1‐week, 1.5‐, 2‐, 3‐, and 4‐weeks post dosing. The severity of cisplatin‐related histopathologic damage (proximal tubule regeneration, degeneration, dilatation, vacuolization and/or interstitial inflammation) increased significantly at 72‐hours post dosing and decreased thereafter. IHC labeling showed increased renal kidney injury molecule‐1 (KIM‐1) expression at 72‐hours, lower expression at 1‐week post dosing, and decreased to insignificant levels of expression thereafter. Concentrations of urinary albumin, lipocalin‐2, osteopontin, KIM‐1, glutathione S‐transferases (αGST and GSTYb1), renal papillary antigen‐1 (RPA‐1), clusterin, β2‐microglobulin, cystatin‐C, gamma glutamyl transferase (GGT), glucose (GLU), N‐acetyl‐beta‐D‐glucosaminidase (NAG), and total protein (TP) were measured and normalized to the concentration of urinary creatinine. Both urinary KIM‐1 and αGST were significantly elevated at 72‐hours post dosing and decreased at subsequent times. This work demonstrated various parameters that may be used to positively identify reversible cisplatin‐induced AKI in rats.