{'fraction_non_alphanumeric': 0.02147074610842727, 'fraction_numerical': 0.00322061191626409, 'mean_word_length': 6.338582677165355, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Putative role of proteolysis and inﬂammatory response in the toxicity of nerve and blister chemical warfare agents: implications for multi‐threat medical countermeasures

Despite the contrasts in chemistry and toxicity, for blister and nerve chemical warfare agents there may be some analogous proteolytic and inﬂammatory mediators and pathological pathways that can be pharmacological targets for a single‐drug multi‐threat medical countermeasure. The dermal–epidermal separation caused by proteases and bullous diseases compared with that observed following exposure to the blister agent sulfur mustard (2,2′‐dichlorodiethyl sulﬁde) has fostered the hypothesis that sulfur mustard vesication involves proteolysis and inﬂammation. In conjunction with the paramount toxicological event of cholinergic crisis that causes acute toxicity and precipitates neuronal degeneration, both anaphylactoid reactions and pathological proteolytic activity have been reported in nerve‐agent‐intoxicated animals. Two classes of drugs already have demonstrated multi‐threat activity for both nerve and blister agents. Serine protease inhibitors can prolong the survival of animals intoxicated with the nerve agent soman and can also protect against vesication caused by the blister agent sulfur mustard. Poly (ADP‐ribose) polymerase (PARP) inhibitors can reduce both soman‐induced neuronal degeneration and sulfur‐mustard‐induced epidermal necrosis. Protease and PARP inhibitors, like many of the other countermeasures for blister and nerve agents, have potent primary or secondary anti‐inﬂammatory pharmacology. Accordingly, we hypothesize that drugs with anti‐inﬂammatory actions against either nerve or blister agent might also display multi‐threat efﬁcacy for the inﬂammatory pathogenesis of both classes of chemical warfare agent. Published in 2003 by John Wiley & Sons, Ltd.