Microsomal oxidative stress induced by NADPH is inhibited by nitrofurantoin redox biotranformation
Author
dc.contributor.author
Aracena, P.
Author
dc.contributor.author
Lazo Hernández, Carlos Enrique
Author
dc.contributor.author
Molina Berríos, Alfredo Enrique
Author
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Sepúlveda, D. R.
Author
dc.contributor.author
Reinoso, C.
Author
dc.contributor.author
Larraín, J. I.
Author
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Navarro, J.
Author
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Letelier, M. E.
Admission date
dc.date.accessioned
2019-01-29T13:56:13Z
Available date
dc.date.available
2019-01-29T13:56:13Z
Publication date
dc.date.issued
2014
Cita de ítem
dc.identifier.citation
Free Radical Research, February 2014; 48(2): 129–136
Identifier
dc.identifier.issn
10715762
Identifier
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10292470
Identifier
dc.identifier.other
10.3109/10715762.2013.836695
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/160096
Abstract
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Nitrofurantoin is used in the antibacterial therapy of the urinary tract. This therapy is associated with various adverse eff ects whose
mechanisms remain unclear. Diverse studies show that the nitro reductive metabolism of nitrofurantoin leads to ROS generation. This
reaction can be catalyzed by several reductases, including the cytochrome P450 (CYP450) reductase. Oxidative stress arising from this
nitro reductive metabolism has been proposed as the mechanism underlying the adverse eff ects associated with nitrofurantoin. There is,
however, an apparent paradox between these fi ndings and the ability of nitrofurantoin to inhibit lipid peroxidation provoked by NADPH
in rat liver microsomes. This work was aimed to show the potential contribution of diff erent enzymatic systems to the metabolism of
this drug in rat liver microsomes. Our results show that microsomal lipid peroxidation promoted by NADPH is inhibited by nitrofurantoin in a concentration-dependent manner. This suggests that the consumption of NADPH in microsomes can be competitively promoted by lipid peroxidation and nitrofurantoin metabolism. The incubation of microsomes with NADPH and nitrofurantoin generated
1-aminohidantoin. In addition, the biotransformation of a classical substrate of CYP450 oxidative system was competitively inhibited
by nitrofurantoin. These results suggest that nitrofurantoin is metabolized through CYP450 system. Data are discussed in terms of the in
vitro redox metabolism of nitrofurantoin.