title: Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats.
abstract: BACKGROUND
  Exogenous insulin-like growth factor-I (IGF-I) promotes recovery from ischemic renal injury, but its effect on cisplatin (CDDP)-induced nephrotoxicity and its mechanisms for the attenuation of renal injury are unknown.
  
  
  METHODS
  We administered recombinant human IGF-I (rhIGF-I, 150 micro g/day, i.p.) once a day 24 h prior to and after CDDP (5 mg/kg, i.v.) injection in rats.
  
  
  RESULTS
  The rhIGF-I treatment significantly decreased serum creatinine (0.92 +/- 0.11 vs 1.50 +/- 0.15 mg/dl; P < 0.05), the tubular damage score, and the ratio of apoptotic cells to tubular epithelial cells in the outer stripe of the outer medulla on day 5 ( P < 0.05). rhIGF-I significantly increased the numbers of p21-positive nuclei (5.15 +/- 0.19 vs 3.45 +/- 0.42/x400 high-power field (HPF); P < 0.05) and proliferating cell nuclear antigen (PCNA)-positive nuclei (28.61 +/- 1.89 vs 18.26 +/- 2.14/x400 HPF; P < 0.05), but decreased the number of cyclin D1-positive cells (3.3 +/- 0.3 vs 6.3 +/- 1.7/x400 HPF; P < 0.05) on day 3. rhIGF-I did not alter 5-bromo-3-deoxyuridine (BrdU) incorporation.
  
  
  CONCLUSIONS
  Our findings suggested that rhIGF-I increased renal p21 and PCNA expression, but reduced cyclin D1 expression in CDDP-treated kidneys. Exogenous rhIGF-I may ameliorate renal damage, in part by stopping the cell cycle at G1/S phase. Exogenous insulin-like growth factor-I (IGF-I) promotes recovery from ischemic renal injury, but its effect on cisplatin (CDDP)-induced nephrotoxicity and its mechanisms for the attenuation of renal injury are unknown.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Shizuoka, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasuda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kato
authors.forename: Takehiko
authors.initials: T
authors.lastname: Miyaji
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Akashi
authors.initials: A
authors.lastname: Togawa
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000037:antagonists & inhibitors / Q000097:blood; D019938:Cyclin D1 / Q000037:antagonists & inhibitors; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C493956:CDKN1A protein, human; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D019938:Cyclin D1; D007334:Insulin-Like Growth Factor I; D003404:Creatinine; D001973:Bromodeoxyuridine; D002945:Cisplatin