Free radical formation and toxicity in the limb teratogenicity ofL-NAME: A new mechanistic model of vascular disruption

Fantel, Alan G.; Stamps, L.D.; Tran, Tung Thanh; Mackler, Bruce; Person, Richard; Nekahi, N.

doi:10.1002/1096-9926(200010)62:4<237::aid-tera12>3.0.co;2-v

Cited by 2 publications

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“…nitrotyrosine formation). Based primarily on this work, Fantel and coworkers have developed a theory of NO-based oxidative damage caused by the induction of iNOS followed by ischemia-reperfusiontype injury associated with the generation of reactive nitrogen species (RNS) and reactive oxygen species (ROS) [322,323]. Further, it was hypothesized that the effects of L-NAME are primarily due to direct effects on the fetus and that it was the combined generation of NO (from iNOS induction) and O 2 -that produced the toxic/teratogenic entity (possibly -OONO) [323].…”

Section: B the Teratology Of Nomentioning

confidence: 99%

Interactive Endogenous Small Molecule (Gaseous) Signaling: Implications for Teratogenesis

Fukuto¹,

Collins²

2007

CPD

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Dioxygen (O2) is an exogenously supplied gas with a number of properties that make it valuable as a biological source of energy and as a result much of life has become dependent on this molecule. Nitric oxide (NO), carbon dioxide (CO) and hydrogen sulfide (H2S) are small molecules that are sometimes in a gaseous state and that can be either exogenously or endogenously supplied. The chemistry of these four molecules allows them to share some common biological targets and signal transduction pathways as well as providing for unique aspects to the biochemistry of each one. Dioxygen can be teratogenic either in excess (hyperoxia) or in deficiency (hypoxia). Although there is a great deal known about the chemistry and physiology of dioxygen, the mechanisms by which it induces toxic endpoints, such as teratogenesis, are unknown. This review examines some fundamental concepts of these four signaling molecules and considers some of the molecular targets and pathways by which they interact. The information regarding the teratogenicity of either excess or deficiency of the four gases is summarized. Interaction information is generally unavailable for teratogenicity endpoints with the four gases and also a mechanistic understanding of the toxicodynamics of the compounds is lacking. Although it could be theoretically predicted that certain interactions would be additive, for example carbon monoxide and hypoxia, based on the physiological role of these molecules, the data is unavailable. Consequently, these small (gaseous) signaling molecules have been demonstrated to interact with respect to signaling pathways, but whether this indicates a similar result for teratogenesis remains unevaluated.

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Section: B the Teratology Of Nomentioning

confidence: 99%

Interactive Endogenous Small Molecule (Gaseous) Signaling: Implications for Teratogenesis

Fukuto¹,

Collins²

2007

CPD

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Further evidence for the role of free radicals in the limb teratogenicity of L‐NAME

Fantel

Person

2002

Teratology

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These findings support the role of excess reactive oxygen species (ROS) formation in L-NAME-induced limb reduction. We propose that nitric oxide (NO) depletion by L-NAME interferes with vascular integrity, and causes vasoconstriction. Resultant hypoxia stimulates superoxide formation and nitric oxide formation catalyzed by the inducible isoform of nitric oxide synthase. The reduction products of superoxide or the products of its reaction with nitric oxide oxidize or nitrate endothelial components resulting in limb reduction defects.

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Free radical formation and toxicity in the limb teratogenicity ofL-NAME: A new mechanistic model of vascular disruption

Cited by 2 publications

References 0 publications

Interactive Endogenous Small Molecule (Gaseous) Signaling: Implications for Teratogenesis

Interactive Endogenous Small Molecule (Gaseous) Signaling: Implications for Teratogenesis

Further evidence for the role of free radicals in the limb teratogenicity of L‐NAME

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