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Age‐Related Differences in Cisplatin‐Induced Renal Toxicity in Rats
Author(s) -
Espandiari Parvaneh,
Zhang Jun,
Rosenzweig Barry A,
Zhou Yuzhao,
Vaidya Vishal S,
Schnackenberg Laura,
Goering Peter L,
Brown Ronald P,
Bonventre Joseph V,
Herman Eugene H,
Beger Richard D,
Thompson Karol L,
Hanig Joseph,
Sadrieh Nakissa
Publication year - 2008
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.22.1_supplement.917.7
Subject(s) - nephrotoxicity , toxicity , creatinine , kidney , medicine , endocrinology , urinary system , cisplatin , necrosis , body weight , chemotherapy
A multi‐age rat model was developed and utilized to examine potential age‐dependent differences in drug‐induced renal toxicity caused by cisplatin. Male Sprague‐Dawley rats (10‐, 25‐, 40‐, and 80‐days‐old) were dosed with 0, 1, 3 and 6 mg/kg i.p. cisplatin (cip). The high dose of cip (6 mg/kg) caused: decreased body weight (all ages); decreased kidney weight/body weight (80‐days‐old); moderate to severe renal lesions (tubular necrosis and apoptosis) (all ages except 25‐days‐old); significantly increased serum BUN and creatinine levels (80‐ and 40‐days‐old). This dose also caused increases in the urinary level of the renal biomarkers: kidney injury molecule‐1 (Kim‐1), renal papillary antigen‐1 (RPA‐1) and N‐acetyl‐beta‐D‐glucosaminidase (NAG) in 40‐ (72 hrs) and 80‐ (48 and 72 hrs) day‐old rats; increases only in NAG and RPA‐1 occurred in 25‐day‐old rats (72 hrs). Significant increases in the gene expression levels of 4 nephrotoxicity biomarkers (Kim‐1, Spp1, Lcn2, Clu) were detected in the kidneys from all age groups (except for 25‐days‐old) treated with 6 mg/kg cip. In addition, similar gene expression levels were observed in 40‐ and 80‐day‐old rats given 3 mg/kg cip. Glucosuria and hydroxyprolinuria were detected on day 2 and 3 in 40‐ and 80‐day‐old rats. These findings indicate that certain biomarkers can help identify these age‐related differences in susceptibility.