Acta Pharmacologica Sinica (2009) 30: 1559–1565; doi: 10.1038/aps.2009.156

Acta Pharmacologica Sinica (2009) 30: 1559–1565; doi: 10.1038/aps.2009.156

Original Article

β-Naphthoflavone protects mice from aristolochic acid-I-induced acute kidney injury in a CYP 1A dependent mechanism

Ying XIAO^{1,2, #}, Xiang XUE^{1,2, #}, Yuan-feng WU^1,2, Guo-zheng XIN^1,2, Yong QIAN³, Tian-pei XIE³, Li-kun GONG^1,*, Jin REN^1,*

¹Centre for Drug Safety and Evaluation Research, State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; ²Graduate School of the Chinese Academy of Sciences, Shanghai 201203, China; ³Shanghai TenGen Biomedical Co Ltd, China

Aim:The role of CYP 1A in the protection of aristolochic acid (AA)I-induced nephrotoxicity has been suggested. In the present study we investigated the effects of β-naphthoflavone (BNF), a non-carcinogen CYP 1A 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 CYP 1A 1 and CYP 1A 2 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 CYP 1A 1 in both liver and kidney; but the induction of CYP 1A 2 was only observed in liver.

Conclusion: BNF prevents AAI-induced kidney toxicity primarily through CYP 1A induction.

Keywords: aristolochic acid; kidney injury; beta-naphthoflavone; biotransformation; CYP 1A

We thank Prof Yi-zheng WANG for reading the manuscript, Prof Xiao-yan CHEN and Prof Da-fang ZHONG for providing the LC-MS/MS system, Yu-Ya WANG, Hua SHENG, Hen-Lei LU, Jin LU for technical assistance. This work was supported by National Grand Fundamental Research 973 Program of China (No 2006CB504700) and Key projects of National Science and Technology Pillar Program (2008ZX09305-007 and 2009ZX09501-033)

^#These authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail lkgong@mail.shcnc.ac.cn (Li-kun GONG); jren@mail.shcnc.ac.cn (Jin REN)
Received 2009-05-19 Accepted 2009-09-21

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