IN VIVO ASSESSMENT OF SKIN CHEMICAL BURNS IN EXPOSURE TO VESICANTS AND THE EFFICACY OF AN ANTIDOTE FORMULA IN DIFFERENT PHARMACEUTICAL FORMS. AN EXPERIMENTAL APPROACH
CRISTINA ANCA SECARĂ 1#, ANA MARIA CATRINA 1, OANA CRISTINA VOINEA 1,2, SONIA SPANDOLE DINU 1, ANDREEA CAMELIA HÎRJĂU 1, LUIZA GEORGIA ȘERBĂNESCU 2,3, DRAGOS SERBAN 2,4*, GABRIEL CATALIN SMARANDACHE 2,4, CERASELA HAIDOIU 1, SPERANTA RADU 1, CORNELIU TUDOR 4#, DANIEL OVIDIU COSTEA 5#, MEDA COMANDASU 4, ANA MARIA DASCALU 2,4, ANDREEA PĂUNA 2, MIHAIL SILVIU TUDOSIE 2
1“Cantacuzino” National Medical-Military Research-Development Institute, 050096 Bucharest, Romania
2“Carol Davila” University of Medicine and Pharmacy,020021 Bucharest, Romania
3“Prof. dr. Al. Trestioreanu” Oncological Institute, 022328 Bucharest, Romania
4University Emergency Hospital Bucharest, 050098 Bucharest, Romania
5Department of General Surgery, Faculty of Medicine, “Ovidius” University, 900470 Constanța, Romania 6First Surgery Department, Emergency County Hospital, 900591 Constanța, Romania
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Abstract
The aim of this project was the histopathological and immunofluorescence evaluation of the cutaneous toxicity of the vesicant chemical compound 2-chloroethyl-ethyl sulphide (CEES), a yperite simulator, and the effectiveness of the applied antidote. A complex antidote formula was developed, the treatment offered 100% protection in case of exposure to 1DL50 chemical vesicant. The histopathological evaluation showed that the association of the newly developed antidote with antioxidant and anti-inflammatory actions with the antidotic formulation, in the form of gel, with regenerating, moisturizing and epithelializing actions, is beneficial for 0.25 - 1 LD50 2-chloroethyl-ethyl sulphide concentrations. Immunofluorescence evaluation of the expression of anti-c-ROS-1 and anti-PARP-1 antibodies, respectively, highlighted the antidysplastic reepithelialising and nuclear stabilizing protective effect of the complex antidote on the skin lesions induced by the studied vesicant compound. The combination of the two complex curative antidotes (A1 formulated as a solution and A2 formulated as a hydrogel) developed within the project has superior therapeutic efficacy. It can guide the therapeutic conduct in case of exposure to vesicant chemicals.