OPTIMIZATION OF ANTIDOTISM IN CASES OF SKIN INJURIES CAUSED BY BLISTER AGENTS. EXPERIMENTAL STUDY
MIHAI-SILVIU TUDOSIE 1, SIMONA BICHERU 2, RUXANDRA AVRAM 3, OANA AVRAM 1,3, CAMELIA ANDREEA VĂRZARU 2, CRISTINA ANCA SECARĂ 2, DRAGOȘ ȘERBAN 1,4*, GABRIEL CĂTĂLIN SMARANDACHE 1,4, CIPRIAN TĂNĂSESCU 5, DRAGOŞ MARIAN POPESCU 6, CORNELIU TUDOR 4, ANA MARIA DASCĂLU 1, CRISTINEL DUMITRU BADIU 1,7
1.“Carol Davila” University of Medicine and Pharmacy Bucharest, Romania
2.“Cantacuzino” National Medical-Military Research-Development Institute Bucharest, Romania
3.Emergency Clinic Hospital Bucharest, Romania
4.IVth Department of General Surgery, Emergency University Hospital Bucharest, Romania
5.“Lucian Blaga” University of Medicine and Pharmacy Sibiu, Romania
6.University of Medicine and Pharmacy Craiova, Romania
7.Department of General Surgery, “Bagdasar-Arseni” Emergency Hospital Bucharest, Romania
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The molecular mechanisms involved in the appearance of oedema and blisters induced by the mustard gas are not fully elucidated, which justifies the difficulty of identifying effective medical countermeasures for the treatment of skin lesions. The paper aims to compare the skin toxicity produced by the chemical compound mustard gas and its synthetic analogue 2clorethyl-ethyl sulphide (CEES), as well as the development and experimental testing of a transdermally absorbed therapeutic formula, whose components pharmacodynamically antagonize the toxicity of these compounds. The experimental results highlighted the following: the synthetic analogue 2-clorethyl-ethyl sulphide (CEES), due to its lower toxicity, is a valid alternative for the laboratory study of blistering chemicals; in vitro evaluation of cell viability in case of CEES exposure revealed cytotoxicity correlated with the dose partially antagonized by the administration of the complex antidote; contamination of the skin with doses of 4.5 µL/cm2 mustard gas and 10 µL/cm2 CEES, respectively, did not produce aggressions such as chain breaks in the DNA; the in vivo assessment of the toxicity of mustard and its synthetic analogue CEES revealed that the administration of the complex antidote showed 30% protection for mustard gas and 100% for CEES in case of percutaneous administration of the average lethal dose (LD50). The histopathological examination showed that the therapeutic effect generated on chemically assaulted areas is predominant by limiting ulcers and inflammation.
