Скринінгове дослідження фригопротекторних властивостей нестероїдних протизапальних препаратів за гострого загального охолодження

2019 
Cold traumas (CT) are quite frequent among the population of Ukraine. Its’ occurrence grows up in winter, when number of injured reaches more then 12 000 people. CT is commonly observed in young people of working age, causes high frequency of disability and requires high costs for treatment. Most of the injured need hospital treatment, mortality is excess 10 % of cases. In conditions of war CT is especially dangerous. It can cause up to 25 % of sanitary losses even in modern armies. Research as to the pathophysiology of frostbite has revealed notable similarities with the inflammatory processes seen in burn injuries and ischaemia/reperfusion injury. Evidence for the role of tromboxanes and prostaglandins has resulted in a more active approach to the medical treatment of frostbite. Considering the role of eicosanoids in the development of cold trauma we can assume positive influence of NSAIDs for such pathology. The aim of the work is to compare the power of frigoprotective effect of NSAIDs with different selectivity to COX using the model of acute general cooling (AGC). The experiment was carried out using healthy white mice weighing 20–24 g during single day from 12.00 till 18.00. Mice were put into individual 500 cm3 plastic cages with free access to air. Cages were situated inside the freezer «Nord Inter-300» with transparent top at a temperature of –18 °C. An integral index of frigoprotective effect was chosen duration of life. Some NSAIDs were used in the experiment: nonselective inhibitors of COX – acetylsalicylic acid (Aspirin, tablets, «Bayer», Germany), ibuprofen (Brufen, powder, «Abbott», USA), mefenamic acid (Mefenamic acid-Darnitsa, tablets, «Darnitsa», Ukraine), diclofenac sodium (Voltaren, tablets, «Novartis», Switzerland); moderately selective inhibitor of COX – meloxicam (Movalis, tablets, «Boehringer Ingelheim», Germany); highly selective inhibitor of COX – celecoxib (Celebrex, tablets, «Pfizer», USA). The results of the present study indicated two NSAIDs with significant frigoprotective effect: celecoxib (74 mg/kg) and diclofenac sodium (14 mg/kg). They increased duration of life of the experimental animals under AGC by more than 50 %.That is reliably higher than effect of Aspirin (25 mg/kg). These two drugs were chosen as a perspective for future in-depth studies of frigoprotective activity. As a conclusion we can say that frigorprotective properties of NSAIDs are highly different and don’t demonstrate strict dependency with level of selectivity to COX; the highest frigoprotective effect were demonstrated by celecoxib (74 mg/kg intragastrically) and diclofenac sodium (14 mg/kg).
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