The protective effect of pyrimidine nucleosides on human HaCaT keratinocytes treated with 5-FU.
BACKGROUND
Therapy with 5-fluorouracil (5-FU) and capecitabine is often complicated by skin toxicity (hand-foot syndrome, HFS). Topical application of uridine ointment is beneficial for alleviating HFS and other pyrimidine nucleosides have been described as 5-FU toxicity modulators. We tested pyrimidine nucleosides and their combinations to find the best combination for topical therapy of HFS.


METHODS
Cellular viability was measured by the real-time cell analyser and methyl thiazol tetrazolium (MTT) assay in order to evaluate the effect of pyrimidine nucleosides on HaCaT keratinocytes treated with 5-FU. The results were confirmed by evaluation of the cellular colonization by microphotography.


RESULTS
Cytidine and uridine protected keratinocytes to the same extent. Thymidine enhanced the protective effect when added to cytidine or uridine. Deoxycytidine did not have any protective effect.


CONCLUSIONS
Our findings support the rationale for using uridine or cytidine in combination with thymidine in ointment for HFS treatment.
Department of Clinical Pharmacology and Pharmacy, General Teaching Hospital, Prague, Czech Republic First Faculty of Medicine, Charles University, Prague, Czech Republic hartinger.jan@vfn.cz.
Jan
J
Hartinger
Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
Pavel
P
Veselý
Department of Clinical Pharmacology and Pharmacy, General Teaching Hospital, Prague, Czech Republic First Faculty of Medicine, Charles University, Prague, Czech Republic.
Irena
I
Netíková
Prague Burn Centre, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Eva
E
Matoušková
First Faculty of Medicine, Charles University, Prague, Czech Republic Department of Oncology, General Teaching Hospital, Prague, Czech Republic.
Luboš
L
Petruželka
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D002478:Cells, Cultured; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000502:physiology; D005472:Fluorouracil / Q000009:adverse effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D011741:Pyrimidine Nucleosides / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D000964:Antimetabolites, Antineoplastic; D011741:Pyrimidine Nucleosides; D013778:Tetrazolium Salts; D013844:Thiazoles; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; C022616:thiazolyl blue; D005472:Fluorouracil
5-FU; Hand-foot syndrome; cytidine; deoxycytidine; keratinocytes; thymidine; uridine