Tissue specific accumulation of hydroxyurea in elasmobranchs
Hydroxyurea is an antibiotic and antiproliferative agent used clinically in the treatment of select cancers, sickle cell anemia, HIV, and myeloproliferative diseases. Hydroxyurea has never been detected in elasmobranch tissues and has only been detected in trace amounts in a single eukaryote. Using the colorimetric assay for hydroxyurea determination originally described by Fabricius and Rajewsky (1971), hydroxyurea was found at relatively high levels in the plasma and tissues of marine, freshwater and euryhaline elasmobranchs and confirmed by gas chromatography-mass spectrometry. The presence of marginal amounts of hydroxyurea in the liver of a teleost (Oncorhynchus mykiss), and absence in a holostean (Amia calva), and a dipnoan (Protopterus dolloi) suggest elasmobranchs may be unique in their ability to accumulate hydroxyurea. In adult little skates (Leucoraja erinacea), hydroxyurea was found to accumulate predominantly in the spiral valve, liver, plasma, rectal gland and stomach to levels ranging from 60-250 µM. Levels of hydroxyurea accumulated in L. erinacea are high enough to have antineoplastic and antimicrobial effects. These findings provide evidence that hydroxyurea may be an important component of the innate immune response of elasmobranchs.