title: Expression of Renal Aquaporins in Aristolochic Acid I and Aristolactam I-Induced Nephrotoxicity.
abstract: BACKGROUND
  Exposure to aristolochic acid (AA) can cause AA nephropathy, which is characterized by extensive proximal tubular damage and polyuria.
  
  
  METHODS
  To test the hypothesis that polyuria might be induced by altered regulation of aquaporins (AQPs) in the kidney, different doses of AA-I or aristolactam I (AL-I) were administered intraperitoneally to Sprague-Dawley rats, and urine, blood, and kidney samples were analyzed. In addition, AQP1, AQP2, AQP4 and AQP6 expression in the kidney were determined.
  
  
  RESULTS
  The results showed dose-dependent proximal tubular damage and polyuria in the AA-I- and AL-I-treated groups, and the nephrotoxicity of AL-I was higher than that of AA-I. The expression of renal AQP1, AQP2 and AQP4, but not AQP6 were significantly inhibited by AA-I and AL-I. Comparison of the inhibition potencies of AA-I and AL-I showed that AL-I was a stronger inhibitor of AQP1 expression than AA-I, while there was no difference in their effects on AQP2 and AQP4.
  
  
  CONCLUSIONS
  These results suggested that AA induced renal damage and polyuria were associated with a specific decrease in the expression of renal AQP1 AQP2 and AQP4, and AL-I showed higher nephrotoxicity than AA-I, which might be attributable to the differences in their inhibition of AQP1.
authors.affiliation: Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, Nanjing, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: ZhenZhou
authors.initials: Z
authors.lastname: Jiang
authors.forename: XiuQin
authors.initials: X
authors.lastname: He
authors.forename: LuYong
authors.initials: L
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism*; D034341:Aristolochic Acids / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020346:Aquaporins; D034341:Aristolochic Acids; C000228:aristolochic acid I