Исследование эстеразного статуса организма как комплексного биомаркера воздействия фосфорорганических соединений
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Аннотация
Разработка системы биомаркеров воздействия фосфорорганических соединений (ФОС) на человека и их количественная оценка являются важным компонентом предсказания и ранней диагностики заболеваний, вызываемых антихолинэстеразными соединениями. Целью нашей работы было исследование эстеразного статуса организма как комплексного биомаркера воздействия ФОС для диагностики воздействия и последующей терапии такого рода интоксикаций. Мы полагаем, что этот комплексный биомаркер будет более эффективным и информативным по сравнению со стандартным определением бутирилхолинэстеразы плазмы крови (БХЭ), ацетилхолинэстеразы эритроцитов (АХЭ) и нейротоксичной эстеразы лимфоцитов (НТЭ). Он позволит: 1) подтвердить или опровергнуть сам факт воздействия ФОС; 2) определить, обусловлено ли воздействие агентами, вызывающими острую и/или отставленную нейротоксичность; 3) провести дозиметрию воздействия, которая даст ценную информацию для последующей терапии отравления. Для подтверждения этой гипотезы мы провели исследование изменения активности АХЭ, НТЭ, БХЭ и карбоксиэстеразы (КЭ) крови мышей через 1 ч после внутрибрюшинного введения возрастающих доз трёх ФОС с различным эстеразным профилем: известного нейропатичного соединения O,O-дипропил-O-дихлорвинилфосфата (C3H 7O)2P(O)OCH=CCl2 (diPr-DClVP) в качестве контрольного соединения и двух модельных диалкилфосфатов – (C2H5O)2P(O)OCH(CF3)2 (diEt-PFP) и (C4H9O)2P(O)OCH(CF3)2 (diBu-PFP). Измерение активности эстераз проводили в препаратах гемолизованной крови спектрофотометрическим (АХЭ, БХЭ, КЭ) и биосенсорным (НТЭ) методами. Анализ полученных дозозависимостей для ингибирования эстераз крови показал, что БХЭ и КЭ являются наиболее чувствительными биомаркерами, позволяющими детектировать низкие дозы ФОС токсикантов. Одновременное определение активности АХЭ и НТЭ в крови может быть использовано для оценки вероятности воздействия острых и/или отставленных нейротоксикантов.
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