Proinflammatory cytokine responses in skin and epidermal cells following epicutaneous administration of anticoagulant rodenticide warfarin in rats
2015
Аутори:
Popov Aleksandrov, AleksandraTusup, Marina
Mirkov, Ivana
Djokic, Jelena
Ninkov, Marina
Zolotarevski, Lidija
Kataranovski, Dragan S.
Kataranovski, Milena
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Context: Dermal toxicity of coumarin anticoagulant rodenticides, such as
warfarin, represents potential risk for workers handling these agents
and for individuals applying easily available rodenticides in their
households as well.
Objective: In this study, proinflammatory effects of repeated
epicutaneous administration of warfarin in rats were explored by
examining inflammatory cytokine skin responses.
Materials and methods: Ex vivo production of IL-1 beta, IL-6, TNF-alpha
and IL-17 by skin explants and by epidermal cells isolated by enzyme
(dispase/trypsin) digestion from skin repeatedly (once a day, three
consecutive days) exposed to 10 mu g of warfarin was measured 24 h and
72 h following the last warfarin application by ELISAs for respective
rat cytokines.
Results: Warfarin treatment resulted in histological changes, but skin
or epidermal cell viability were not compromised, judging by MTT
reduction assay. Both skin and epidermal cells responded to
administration of this agent by production of all examined inflammatory
cytokines (skin explants by TNF-alpha and IL-17; epidermal cells by IL-1
beta and TNF-alpha) except IL-6. Discussion: Along with
histomorphological changes, cytokines indicate functional consequences
in treated skin. IL-1 beta production, that precede production of
TNF-alpha, might be responsible for production of the latter cytokine.
Sustained production of IL-1 beta suggests persistence of epidermal cell
stimulation or existence of some amplification mechanisms. Requirements
for T cells seem to exist concerning epidermal cell IL-17 production.
Conclusion: Presented data provide additional new information concerning
proinflammatory effects of warfarin.
Кључне речи:
Epidermal cells; rats; skin; warfarinИзвор:
Cutaneous and Ocular Toxicology, 2015, 34, 2, 149-155
DOI: 10.3109/15569527.2014.928307
ISSN: 1556-9535