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2015 ; 10
(11
): e0142890
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Widespread Natural Occurrence of Hydroxyurea in Animals
#MMPMID26600157
Fraser DI
; Liu KT
; Reid BJ
; Hawkins E
; Sevier A
; Pyle M
; Robinson JW
; Ouellette PH
; Ballantyne JS
PLoS One
2015[]; 10
(11
): e0142890
PMID26600157
show ga
Here we report the widespread natural occurrence of a known antibiotic and
antineoplastic compound, hydroxyurea in animals from many taxonomic groups.
Hydroxyurea occurs in all the organisms we have examined including invertebrates
(molluscs and crustaceans), fishes from several major groups, amphibians and
mammals. The species with highest concentrations was an elasmobranch (sharks,
skates and rays), the little skate Leucoraja erinacea with levels up to 250 ?M,
high enough to have antiviral, antimicrobial and antineoplastic effects based on
in vitro studies. Embryos of L. erinacea showed increasing levels of hydroxyurea
with development, indicating the capacity for hydroxyurea synthesis. Certain
tissues of other organisms (e.g. skin of the frog (64 ?M), intestine of lobster
(138 ?M) gills of the surf clam (100 ?M)) had levels high enough to have
antiviral effects based on in vitro studies. Hydroxyurea is widely used
clinically in the treatment of certain human cancers, sickle cell anemia,
psoriasis, myeloproliferative diseases, and has been investigated as a potential
treatment of HIV infection and its presence at high levels in tissues of
elasmobranchs and other organisms suggests a novel mechanism for fighting disease
that may explain the disease resistance of some groups. In light of the known
production of nitric oxide from exogenously applied hydroxyurea, endogenous
hydoxyurea may play a hitherto unknown role in nitric oxide dynamics.
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