TY  - JOUR
AU  - Zolotarevski, Lidija
AU  - Jović, Milena
AU  - Popov Aleksandrov, Aleksandra
AU  - Milosavljević, Petar
AU  - Brajušković, Goran
AU  - Demenesku, Jelena
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://www.tandfonline.com/doi/full/10.3109/15569527.2015.1008701
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2971
AB  - CONTEXT: Skin is the target of both acute and chronic exposure to warfarin, coumarin anticoagulant. Single exposure of rat skin to this agent induces early (24 h following epicutaneous administration) local response which might be part of inflammatory/reparatory homeostatic program or introduction to pathological events in exposed skin. OBJECTIVE: To examine time-dependent changes in skin of rats exposed to epicutaneously applied warfarin. MATERIALS AND METHODS: The effect of low (10 μg) and high (100 μg) doses of warfarin on histologically evident changes of epidermis (epidermal thickness) and dermis (numbers of mesenchymal cells and dermal capillaries), skin cell proliferative activity (Ki67(+) and PCNA(+) cells) and apoptotic (TUNEL(+)) and necrotic (ultra structural appearance) cells was examined one, three and seven days after the application. RESULTS: Both warfarin doses affected the majority of skin cell activity, but with differential time-course of skin epidermal and dermal cells state/activity. The occurrence of necrotic/apoptotic epidermal and dermal cells was noted the first day after the application and the activities which point to tissue reparation/remodeling were observed seven days after skin exposure to this agent. DISCUSSION: The observed pattern of changes (early evidence of cell/tissue injury which was later followed by signs of cell activity characteristic for tissue reparation/remodeling) implied warfarin-induced toxicity in skin cells as stimulus for subsequent activities relevant for tissue homeostasis. CONCLUSION: The data presented provide new and additional information concerning skin responses to warfarin that gains access to this tissue.
T2  - Cutaneous and Ocular Toxicology
T2  - Cutaneous and Ocular Toxicology
T1  - Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity.
IS  - 1
VL  - 35
DO  - 10.3109/15569527.2015.1008701
SP  - 41
EP  - 48
ER  - 

@article{
author = "Zolotarevski, Lidija and Jović, Milena and Popov Aleksandrov, Aleksandra and Milosavljević, Petar and Brajušković, Goran and Demenesku, Jelena and Mirkov, Ivana and Ninkov, Marina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "CONTEXT: Skin is the target of both acute and chronic exposure to warfarin, coumarin anticoagulant. Single exposure of rat skin to this agent induces early (24 h following epicutaneous administration) local response which might be part of inflammatory/reparatory homeostatic program or introduction to pathological events in exposed skin. OBJECTIVE: To examine time-dependent changes in skin of rats exposed to epicutaneously applied warfarin. MATERIALS AND METHODS: The effect of low (10 μg) and high (100 μg) doses of warfarin on histologically evident changes of epidermis (epidermal thickness) and dermis (numbers of mesenchymal cells and dermal capillaries), skin cell proliferative activity (Ki67(+) and PCNA(+) cells) and apoptotic (TUNEL(+)) and necrotic (ultra structural appearance) cells was examined one, three and seven days after the application. RESULTS: Both warfarin doses affected the majority of skin cell activity, but with differential time-course of skin epidermal and dermal cells state/activity. The occurrence of necrotic/apoptotic epidermal and dermal cells was noted the first day after the application and the activities which point to tissue reparation/remodeling were observed seven days after skin exposure to this agent. DISCUSSION: The observed pattern of changes (early evidence of cell/tissue injury which was later followed by signs of cell activity characteristic for tissue reparation/remodeling) implied warfarin-induced toxicity in skin cells as stimulus for subsequent activities relevant for tissue homeostasis. CONCLUSION: The data presented provide new and additional information concerning skin responses to warfarin that gains access to this tissue.",
journal = "Cutaneous and Ocular Toxicology, Cutaneous and Ocular Toxicology",
title = "Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity.",
number = "1",
volume = "35",
doi = "10.3109/15569527.2015.1008701",
pages = "41-48"
}

Zolotarevski, L., Jović, M., Popov Aleksandrov, A., Milosavljević, P., Brajušković, G., Demenesku, J., Mirkov, I., Ninkov, M., Kataranovski, D.,& Kataranovski, M.. (2016). Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity.. in Cutaneous and Ocular Toxicology, 35(1), 41-48.
https://doi.org/10.3109/15569527.2015.1008701

Zolotarevski L, Jović M, Popov Aleksandrov A, Milosavljević P, Brajušković G, Demenesku J, Mirkov I, Ninkov M, Kataranovski D, Kataranovski M. Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity.. in Cutaneous and Ocular Toxicology. 2016;35(1):41-48.
doi:10.3109/15569527.2015.1008701 .

Zolotarevski, Lidija, Jović, Milena, Popov Aleksandrov, Aleksandra, Milosavljević, Petar, Brajušković, Goran, Demenesku, Jelena, Mirkov, Ivana, Ninkov, Marina, Kataranovski, Dragan, Kataranovski, Milena, "Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity." in Cutaneous and Ocular Toxicology, 35, no. 1 (2016):41-48,
https://doi.org/10.3109/15569527.2015.1008701 . .

TY  - JOUR
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Zolotarevski, Lidija D
AU  - Jović, Milena
AU  - Belij, Sandra
AU  - Kataranovski, Dragan S.
AU  - Kataranovski, Milena
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1299
AB  - Objective: To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods: Rats were exposed to warfarin by applying 10 mu g of warfarin-sodium to 10-12 cm(2) skin (range 0.8-1 mu g per 1 cm(2)) for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results: Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury (increased malondialdehyde, MDA, production, evident histo-morphological changes in epidermis and dermis depicting cell injury and death). Increased numbers of proliferating cell nuclear antigen (PCNA(+)) cells indicated reparative processes in injured skin. Infiltration of CD3(+) cells (T lymphocytes) along with the increased production of tumor necrosis factor-alpha (TNF-alpha) by epidermal cells from warfarin-treated skin and their co-stimulatory effect in an in vitro T-cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion: Presented data have documented tissue damage associated with immune/inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.
T2  - Biomedical and Environmental Sciences
T1  - Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats
IS  - 2
VL  - 24
EP  - 189
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1299
ER  - 

@article{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Zolotarevski, Lidija D and Jović, Milena and Belij, Sandra and Kataranovski, Dragan S. and Kataranovski, Milena",
year = "2011",
abstract = "Objective: To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods: Rats were exposed to warfarin by applying 10 mu g of warfarin-sodium to 10-12 cm(2) skin (range 0.8-1 mu g per 1 cm(2)) for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results: Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury (increased malondialdehyde, MDA, production, evident histo-morphological changes in epidermis and dermis depicting cell injury and death). Increased numbers of proliferating cell nuclear antigen (PCNA(+)) cells indicated reparative processes in injured skin. Infiltration of CD3(+) cells (T lymphocytes) along with the increased production of tumor necrosis factor-alpha (TNF-alpha) by epidermal cells from warfarin-treated skin and their co-stimulatory effect in an in vitro T-cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion: Presented data have documented tissue damage associated with immune/inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.",
journal = "Biomedical and Environmental Sciences",
title = "Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats",
number = "2",
volume = "24",
pages = "189",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1299"
}

Popov Aleksandrov, A., Mirkov, I., Zolotarevski, L. D., Jović, M., Belij, S., Kataranovski, D. S.,& Kataranovski, M.. (2011). Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats. in Biomedical and Environmental Sciences, 24(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1299

Popov Aleksandrov A, Mirkov I, Zolotarevski LD, Jović M, Belij S, Kataranovski DS, Kataranovski M. Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats. in Biomedical and Environmental Sciences. 2011;24(2):null-189.
https://hdl.handle.net/21.15107/rcub_ibiss_1299 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Zolotarevski, Lidija D, Jović, Milena, Belij, Sandra, Kataranovski, Dragan S., Kataranovski, Milena, "Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats" in Biomedical and Environmental Sciences, 24, no. 2 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1299 .

TY  - JOUR
AU  - Kataranovski, Milena
AU  - Kataranovski, Dragan S.
AU  - Zolotarevski, Lidija D
AU  - Jović, Milena
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1615
AB  - Dermatotoxic effects of epicutaneous application of a first generation anticoagulant, warfarin (WF), were examined in rats. Selected parameters of skin activity were determined 24 hours following warfarin application by histomorphological and immunohistochemical analysis and by assessing some aspects of immunomodulatory potential of warfarin in skin. Increased number of mast cells, with degranulation at higher doses of warfarin was noted in warfarin treated skin. Mast cell presence coincided with changes in blood vessels and fibroblast appearance suggesting mast cell activity in warfarin treated skin. Signs of nuclear hypertrophy and anysonucleosys were noted by analysis of PCNA(+) cells in epidermis following warfarin application. Histomorphological changes were accompanied by immunemodulating activity in warfarin treated skin. This was judged by slightly increased numbers of CD3(+) cells in epidermis and superficial dermis and by production of organ cultured full thickness skin explants of factors with costimulatory activity in T-cell activation/proliferation assay. Presented data demonstrates the potential of warfarin to modulate local skin activity in rats.
T2  - Cutaneous and Ocular Toxicology
T1  - Epicutaneous exposure to anticoagulant rodenticide warfarin modulates local skin activity in rats
IS  - 1
VL  - 26
EP  - 13
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1615
ER  - 

@article{
author = "Kataranovski, Milena and Kataranovski, Dragan S. and Zolotarevski, Lidija D and Jović, Milena",
year = "2007",
abstract = "Dermatotoxic effects of epicutaneous application of a first generation anticoagulant, warfarin (WF), were examined in rats. Selected parameters of skin activity were determined 24 hours following warfarin application by histomorphological and immunohistochemical analysis and by assessing some aspects of immunomodulatory potential of warfarin in skin. Increased number of mast cells, with degranulation at higher doses of warfarin was noted in warfarin treated skin. Mast cell presence coincided with changes in blood vessels and fibroblast appearance suggesting mast cell activity in warfarin treated skin. Signs of nuclear hypertrophy and anysonucleosys were noted by analysis of PCNA(+) cells in epidermis following warfarin application. Histomorphological changes were accompanied by immunemodulating activity in warfarin treated skin. This was judged by slightly increased numbers of CD3(+) cells in epidermis and superficial dermis and by production of organ cultured full thickness skin explants of factors with costimulatory activity in T-cell activation/proliferation assay. Presented data demonstrates the potential of warfarin to modulate local skin activity in rats.",
journal = "Cutaneous and Ocular Toxicology",
title = "Epicutaneous exposure to anticoagulant rodenticide warfarin modulates local skin activity in rats",
number = "1",
volume = "26",
pages = "13",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1615"
}

Kataranovski, M., Kataranovski, D. S., Zolotarevski, L. D.,& Jović, M.. (2007). Epicutaneous exposure to anticoagulant rodenticide warfarin modulates local skin activity in rats. in Cutaneous and Ocular Toxicology, 26(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1615

Kataranovski M, Kataranovski DS, Zolotarevski LD, Jović M. Epicutaneous exposure to anticoagulant rodenticide warfarin modulates local skin activity in rats. in Cutaneous and Ocular Toxicology. 2007;26(1):null-13.
https://hdl.handle.net/21.15107/rcub_ibiss_1615 .

Kataranovski, Milena, Kataranovski, Dragan S., Zolotarevski, Lidija D, Jović, Milena, "Epicutaneous exposure to anticoagulant rodenticide warfarin modulates local skin activity in rats" in Cutaneous and Ocular Toxicology, 26, no. 1 (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1615 .