beta-Naphthoflavone protects mice from aristolochic acid-I-induced acute kidney injury in a CYP1A dependent mechanism

  • Acta Pharmacol Sin. 2009 Nov;30(11):1559-65. doi: 10.1038/aps.2009.156.
Ying Xiao  1 ,  Xiang Xue ,  Yuan-feng Wu ,  Guo-zheng Xin ,  Yong Qian ,  Tian-pei Xie ,  Li-kun Gong ,  Jin Ren
Affiliations
  • 1. Centre for Drug Safety and Evaluation Research, State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
PMID: 19890363 DOI: 10.1038/aps.2009.156
Abstract

Aim: The role of CYP1A in the protection of aristolochic acid (AA)I-induced nephrotoxicity has been suggested. In the present study we investigated the effects of beta-naphthoflavone (BNF), a non-carcinogen CYP1A inducer, on AAI-induced kidney injury.

Methods: Mice were pretreated with 80 mg/kg BNF by daily intraperitoneal injection (IP) for 3 days followed by a single IP of 10 mg/kg AAI. AAI and its major metabolites in blood, liver and kidney, the expression of CYP1A1 and CYP1A2 in microsomes of liver and kidney, as well as the nephrotoxicity were evaluated.

Results: BNF pretreatment prevented AAI-induced renal damage by facilitating the disposal of AAI in liver. BNF pretreatment induced the expression of CYP1A1 in both liver and kidney; but the induction of CYP1A2 was only observed in liver.

Conclusion: BNF prevents AAI-induced kidney toxicity primarily through CYP1A induction.

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