About: The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-A comparative study     Goto   Sponge   NotDistinct   Permalink

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  • Aristolochic acid is the cause of aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN) and their associated urothelial malignancies. Using Western blotting, we investigated the expression of NAD(P)H:quinone oxidoreductase (NQO1), the most efficient cytosolic enzyme that reductively activates aristolochic acid I (AAI) in mice and rats. In addition, the effect of AAI on the expression of the NQO1 protein and its enzymatic activity in these experimental animal models was examined. We found that NQO1 protein levels in cytosolic fractions isolated from liver, kidney and lung of mice differed from those expressed in these organs of rats. In mice, the highest levels of NQO1 protein and NQO1 activity were found in the kidney, followed by lung and liver. In contrast, the NQO1 protein levels and enzyme activity were lowest in rat-kidney cytosol, whereas the highest amounts of NQO1 protein and activity were found in lung cytosols, followed by those of liver. NQO1 protein and enzyme activity were induced in liver and kidney of AAI-pretreated mice compared with those of untreated mice. NQO1 protein and enzyme activity were also induced in rat kidney by AAI. Furthermore, the increase in hepatic and renal NQO1 enzyme activity was associated with AAI bioactivation and elevated AAI-DNA adduct levels were found in ex vivo incubations of cytosolic fractions with DNA and AAI. In conclusion, our results indicate that AAI can increase its own metabolic activation by inducing NQO1, thereby enhancing its own genotoxic potential.
  • Aristolochic acid is the cause of aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN) and their associated urothelial malignancies. Using Western blotting, we investigated the expression of NAD(P)H:quinone oxidoreductase (NQO1), the most efficient cytosolic enzyme that reductively activates aristolochic acid I (AAI) in mice and rats. In addition, the effect of AAI on the expression of the NQO1 protein and its enzymatic activity in these experimental animal models was examined. We found that NQO1 protein levels in cytosolic fractions isolated from liver, kidney and lung of mice differed from those expressed in these organs of rats. In mice, the highest levels of NQO1 protein and NQO1 activity were found in the kidney, followed by lung and liver. In contrast, the NQO1 protein levels and enzyme activity were lowest in rat-kidney cytosol, whereas the highest amounts of NQO1 protein and activity were found in lung cytosols, followed by those of liver. NQO1 protein and enzyme activity were induced in liver and kidney of AAI-pretreated mice compared with those of untreated mice. NQO1 protein and enzyme activity were also induced in rat kidney by AAI. Furthermore, the increase in hepatic and renal NQO1 enzyme activity was associated with AAI bioactivation and elevated AAI-DNA adduct levels were found in ex vivo incubations of cytosolic fractions with DNA and AAI. In conclusion, our results indicate that AAI can increase its own metabolic activation by inducing NQO1, thereby enhancing its own genotoxic potential. (en)
Title
  • The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-A comparative study
  • The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-A comparative study (en)
skos:prefLabel
  • The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-A comparative study
  • The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-A comparative study (en)
skos:notation
  • RIV/00216208:11310/14:10282870!RIV15-MSM-11310___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(GA303/09/0472), S
http://linked.open...iv/cisloPeriodika
  • JUL 1 2014
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 13128
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11310/14:10282870
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • DNA adducts; Metabolic activation; Protein expression; NAD(P):quinone oxidoreductase; Aristolochic acid nephropathy (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • NL - Nizozemsko
http://linked.open...ontrolniKodProRIV
  • [00E8090CB4E6]
http://linked.open...i/riv/nazevZdroje
  • Mutation Research - Genetic Toxicology and Environmental Mutagenesis
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 768
http://linked.open...iv/tvurceVysledku
  • Arlt, Volker M.
  • Frei, Eva
  • Schmeiser, Heinz H.
  • Stiborová, Marie
  • Bárta, František
  • Levová, Kateřina
http://linked.open...ain/vavai/riv/wos
  • 000337883400001
issn
  • 1383-5718
number of pages
http://bibframe.org/vocab/doi
  • 10.1016/j.mrgentox.2014.01.012
http://localhost/t...ganizacniJednotka
  • 11310
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