The characteristics of aristolochic acid nephropathy (AAN) are interstitial fibrosis and atrophy of the proximal tubules, but with\r\nno change in glomeruli. To investigate the effects of AA on renal functions and the pharmacokinetics (PKs) of p-aminohippuric\r\nacid (PAH) and inulin, New Zealand white rabbits were used in this study. The plasma concentrations of PAH and inulin were\r\ndetermined by validated HPLC methods. After a single intravenous administration of 0.5 mg/kg aristolochic acid sodium (AANa),\r\nrabbits exhibited mild to moderate nephrotoxicity on the 7th day. Significant tubulointerstitial damage to kidney specimens\r\nwas found, but there were no remarkable glomerular changes. Clearance rates of PAH and inulin both significantly decreased\r\nin AANa-treated rabbits. In addition, there was a significant correlation among the degree of tubulointerstitial changes and PK\r\nparameters of PAH after AANa administration, but no correlation was noted with the PKs of inulin.With mild to moderate AAN\r\nin rabbits, the renal plasma flow significantly decreased by 55%, and the glomerular filtration rate also significantly decreased by\r\n85%. In conclusion, major renal lesions were found on proximal tubules after AANa administration. The PKs of PAH and inulin\r\nsignificantly changed, and kidney functions, including the RPF and GFR, were reduced.
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