Intensity variation of keloids development and nuclear factor NF-kb expression for dermal fibroblasts after using verapamil calcium channel blocking agent
Abstract
The objective of the study was to assess the efficacy of verapamil calcium channel blocker for treatment of keloid scars and to study its effect on the transcription factor NF-kB expression. 134 patients with a burn injury were included into the study. 53 patients were treated by the cream with verapamil topically, and 81patients were applied the conventional therapy. Expression of nuclear transcription factor NF-kB was investigated in a continuous culture of human dermal fibroblasts. Topical application of verapamil demonstrated the stable clinical outcomes with improved nature of scars, their consistency and color, and reduction the number of contractures. There has been established the evident dose- dependent pharmacological effect of verapamil CCBA in inhibition of NF-kB excessive activity, explaining the mechanism of verapamil pleiotropic effect, targeted on suppressing of connective tissues excessive development in keloid scars formation.
References
2. Воронков А.В., Степанова Э.Ф., Жидкова Ю.Ю., Гамзелева О.Ю. Современные подходы фармакологической коррекции патологических рубцов // Фундаментальные ис-следования. - 2014. - №3-2. - С.301-308.
3. Головач И.Ю. Ядерный фактор кВ (NF-kB) как важный патогенетический фактор и новая мишень в лечении ревма¬тических заболеваний // Рациональная фармакотерапия. - 2012. - №3. - С.46-51.
4. Карапетян Г.Э., Пахомова Р.А., Кочетова Л.В. и др. Лечение гипертрофических и келоидных рубцов // Фундаментальные исследования. - 2013. - №3. - С.70-73.
5. Коррекция рубцов / Под ред. К.А. Арндта. - М.: Рид Элсивер, 2009. - 116 с.
6. Barnes PJ. Cellular and molecular mechanisms of chronic obstructive pulmonary disease // Clinics in chest medicine. - 2014. - Vol. 35. №1. - P.71-86.
7. Butler P.D., Longaker M. T., Yang G.P. Current Progress in Keloid Research and Treatment // J Am Coll Surg. - 2008. - Vol. 206. - Р.731-741.
8. Chike-Obi C.J., ColeP.D., BrissettA.E. Keloids: pathogenesis, clinical features, and management // Semin Plast Surg. - 2009. - Vol. 23. - Р.178-184.
9. Duffield J.S., etal. Host responses in tissue repair and fibrosis //Annual review of pathology. - 2013. - Vol. 8. - P.241.
10. Duran-Salgado M.B., Rubio-Guerra A.F. Diabetic nephropathy and inflammation // World J Diabetes. - 2014. - Vol. 5. №3. - P.393-398.
11. Karin M., Lin A. NF-kB at the cross roads of life and death // Nat. Immunol. - 2002. - №3. - P.221-227.
12. Lee Y.S., Hsu T., Chiu W.C., et al. Keloid-derived, plasma/ fibrin-based skin equivalents generate de novo dermal and epidermal pathology ofkeloid fibrosis in a mouse model // Wound Repair and Regeneration. - 2016. - Vol. 24. №2. - P.302-316. - doi: 10.1111/wrr.12397.
13. LiangS.J., et al. Inhibition ofOrai1 Store-Operated Calcium Channel Prevents Foam Cell Formation and Atherosclerosis // Arteriosclerosis, thrombosis, and vascular biology. - 2016. - Vol. 36. №4. - P.618-628.
14. Schisandrin A. Enhances the cytotoxicity of doxorubicin by the inhibition of nuclear factor-kappa В signaling in a doxorubicin- resistant human osteosarcoma cell line // RSC Advances. - 2015. - Vol. 5. №18. - P.13972-13984.
15. Suzuki Y., Inoue T., Ra C. Calcium signaling in mast cells: Focusing on L-type calcium channels // Calcium Signaling. - Springer Netherlands, 2012. - P.955-977.
16. Weber K.T. Sun Y., Bhattacharya S.K., et al. Myofibroblast- mediated mechanisms of pathological remodelling of the heart // Nature Reviews Cardiology. - 2013. - Vol. 10. №1. - P.15-26. - doi: 10.1038/nrcardio.2012.158
REFERENCES
1. Bulankina I.A. Optimization of process of healing wounds of skin in experiment // Sibirskij Medicinskij Zurnal (Irkutsk). - 2007. - Vol. 73. №6. - P.45-48. (in Russian)
2. Voronkov A.V., Stepanova E.F., Zhidkova Y.Y., Gamzeleva O.Y. Modern approaches of pharmacological correction of pathological scars // Fundamental’nye issledovanija. - 2014. - №3-2. - P.301-308. (in Russian)
3. Golovach I. Y. The nuclear factor кВ (NF-kB) as an important pathogenetic factor and a new target in the treatment of rheumatic diseases // Racional’naja farmakoterapija. - 2012. - №3. - P.46-51. (in Russian)
4. Karapetyan G.E., Pakhomova R.A., Kochetova L.V., et al. Treatment hypertrophic and keloidnykh of hems // Fundamental'nye issledovanija. - 2013. - №3. - P.70-73. (in Russian)
5. Correction of scars / Ed. K.A. Arndt. - Moscow: Rid Jelsiver, 2009. - 116 p. (in Russian)
6. Barnes P.J. Cellular and molecular mechanisms of chronic obstructive pulmonary disease // Clinics in chest medicine. - 2014. - Vol. 35. №1. - P.71-86.
7. Butler P.D., Longaker M. T., Yang G.P. Current Progress in Keloid Research and Treatment // J Am Coll Surg. - 2008. - Vol. 206. - Р.731-741.
8. Chike-Obi C.J., Cole P.D., Brissett A.E. Keloids: pathogenesis, clinical features, and management // Semin Plast Surg. - 2009. - Vol. 23. - Р.178-184.
9. Duffield J.S., et al. Host responses in tissue repair and fibrosis //Annual review of pathology. - 2013. - Vol. 8. - P.241.
10. Duran-Salgado M.B., Rubio-Guerra A.F. Diabetic nephropathy and inflammation // World J Diabetes. - 2014. - Vol. 5. №3. - P.393-398.
11. Karin M., Lin A. NF-kB at the cross roads of life and death // Nat. Immunol. - 2002. - №3. - P.221-227.
12. Lee Y.S., Hsu T., Chiu W.C., et al. Keloid-derived, plasma/ fibrin-based skin equivalents generate de novo dermal and epidermal pathology ofkeloid fibrosis in a mouse model // Wound Repair and Regeneration. - 2016. - Vol. 24. №2. - P.302-316. - doi: 10.1111/wrr.12397.
13. LiangS.J., et al. Inhibition ofOrai1 Store-Operated Calcium Channel Prevents Foam Cell Formation and Atherosclerosis // Arteriosclerosis, thrombosis, and vascular biology. - 2016. - Vol. 36. №4. - P.618-628.
14. Schisandrin A. Enhances the cytotoxicity of doxorubicin by the inhibition of nuclear factor-kappa В signaling in a doxorubicin- resistant human osteosarcoma cell line // RSC Advances. - 2015. - Vol. 5. №18. - P.13972-13984.
15. Suzuki Y., Inoue T., Ra C. Calcium signaling in mast cells: Focusing on L-type calcium channels // Calcium Signaling. - Springer Netherlands, 2012. - P.955-977.
16. Weber K.T. Sun Y., Bhattacharya S.K., et al. Myofibroblast- mediated mechanisms of pathological remodelling of the heart // Nature Reviews Cardiology. - 2013. - Vol. 10. №1. - P.15-26. - doi: 10.1038/nrcardio.2012.158