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


CONCLUSIONS
BNF prevents AAI-induced kidney toxicity primarily through CYP1A induction.
Xiao
Ying
Y
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
X
Wu
Yuan-feng
YF
Xin
Guo-zheng
GZ
Qian
Yong
Y
Xie
Tian-pei
TP
Gong
Li-kun
LK
Ren
Jin
J
D000208:Acute Disease; D000818:Animals; D034341:Aristolochic Acids / Q000378:metabolism / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D034341:Aristolochic Acids; D019324:beta-Naphthoflavone; C000228:aristolochic acid I; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2