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PMID: 19890363 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Acta pharmacologica Sinica ·Vol. 30 ·No. 11 ·2009-11-00 ·Pages 1559-65

Xiao Y, Xue X, Wu YF, Xin GZ, Qian Y, Xie TP, Gong LK, Ren J

Abstract

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

MeSH Terms
Acute Disease Animals Aristolochic Acids/metabolism,toxicity Cytochrome P-450 CYP1A1/drug effects,metabolism Cytochrome P-450 CYP1A2/drug effects,metabolism Enzyme Induction/drug effects Injections, Intraperitoneal Kidney/drug effects,metabolism Kidney Diseases/chemically induced,prevention & control Male Mice Mice, Inbred C57BL Microsomes/drug effects,metabolism Microsomes, Liver/drug effects,metabolism beta-Naphthoflavone/pharmacology
Chemicals
Aristolochic Acids beta-Naphthoflavone aristolochic acid I Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1A2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Xiao Ying
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.
Xue Xiang
Wu Yuan-feng
Xin Guo-zheng
Qian Yong
Xie Tian-pei
Gong Li-kun
Ren Jin
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Article Info
Journal
Acta pharmacologica Sinica
Abbr.
Acta Pharmacol Sin
ISSN
1745-7254
DOI
10.1038/aps.2009.156
Published
2009-11-00
Pages
1559-65
Language
English
Region
United States
NLM ID
100956087
PMCID
PMC4003015
Subset
IM
External Links
PubMed source DOI: 10.1038/aps.2009.156 PMC Full Text View journal details
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