safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2024-12-3-299-308safetyrisk-453Research ArticleГЛАВНАЯ ТЕМА: РАЗУМНАЯ ДОСТАТОЧНОСТЬ КАК ПРИНЦИП ЛЕКАРСТВЕННОЙ ТЕРАПИИMAIN TOPIC: REASONABLE SUFFICIENCY AS A PRINCIPLE OF PHARMACOTHERAPYНейротропное действие ботулинического токсина и возможности фармакотерапии ботулизма специфической сывороткой (обзор)Neurotropic Effect of Botulinum Toxin and the Potential of Specific Serum Therapy in Botulism (Review)https://orcid.org/0009-0007-0566-7700ЕлисееваЕ. М.EliseevaE. M.

Елисеева Екатерина Максимовна

Петровский б-р, д. 8, стр. 2, Москва, 127051

Ekaterina M. Eliseeva

8/2 Petrovsky Blvd, Moscow 127051

eliseevaem@expmed.ruhttps://orcid.org/0000-0002-3733-6822МазеркинаИ. А.MazerkinaI. A.

Мазеркина Ирина Анатольевна, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Irina A. Mazerkina, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

mazerkina@expmed.ruhttps://orcid.org/0009-0000-8907-1873ЧистохинаА. А.ChistokhinaA. A.

Чистохина Анна Андреевна

Петровский б-р, д. 8, стр. 2, Москва, 127051

Anna A. Chistokhina 

8/2 Petrovsky Blvd, Moscow 127051

chistokhina@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202403092024123299308Copyright © Елисеева Е.М., Мазеркина И.А., Чистохина А.А., 20242024Елисеева Е.М., Мазеркина И.А., Чистохина А.А.Eliseeva E.M., Mazerkina I.A., Chistokhina A.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/453ВВЕДЕНИЕ

ВВЕДЕНИЕ. Произошедшая в России в июне 2024 года вспышка пищевого ботулизма в очередной раз продемонстрировала опасность этого довольно редкого, но тяжелого инфекционного заболевания, вызываемого попаданием в организм ботулинического нейротоксина. Единственной этиотропной терапией ботулизма в настоящее время является введение антитоксинов к различным серотипам ботулотоксина. Однако при применении антитоксина не наблюдается быстрый регресс неврологической симптоматики, что может вызвать сомнения в эффективности проводимого лечения. Оценить возможности специфической терапии невозможно без понимания механизмов действия ботулотоксина и антитоксина.

ЦЕЛЬ

ЦЕЛЬ. Систематизация информации о механизме повреждающего действия ботулинического нейротоксина, этиотропном лечении антитоксином и процессе восстановления пациентов.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Показано, что механизм повреждающего действия ботулинического нейротоксина заключается в разрушении белков SNARE в пресинаптических окончаниях холинергических нервов, что приводит к нарушению выделения ацетилхолина в синаптическую щель и прекращению передачи возбуждения между нейронами. Отсутствие ацетилхолина в нервно-мышечном синапсе приводит к характерному стойкому вялому мышечному параличу. Специфический механизм действия ботулотоксина определяет тактику лечения, включающую в себя комплекс мероприятий для поддержания жизнеспособности организма и максимально скорое введение противоботулинической сыворотки. Ботулинический антитоксин при применении в течение 48 ч после появления симптомов связывает свободно циркулирующий в крови ботулотоксин, что останавливает прогрессирование паралича и предотвращает развитие дальнейших нарушений у пациентов. Однако антитоксические антитела не могут нейтрализовать действие уже адсорбированного нейротоксина, в связи с чем в течение 12 ч после введения сыворотки клиническая симптоматика может ухудшаться. Восстановление нормальной нейрональной передачи происходит за счет образования новых аксональных окончаний и может занимать длительное время.

ВЫВОДЫ

ВЫВОДЫ. Введение антитоксина незаменимо в этиотропной терапии ботулизма и является эффективным, однако продолжительность восстановительного периода зависит от скорости процесса реиннервации нервно-мышечной передачи.

INTRODUCTION

INTRODUCTION. The outbreak of foodborne botulism that occurred in Russia in June 2024 once again demonstrated the danger of this rather rare but severe infectious disease caused by ingesting botulinum neurotoxin. The only aetiological treatment for botulism is currently the administration of antitoxins against various serotypes of botulinum toxin. However, antitoxins do not provide rapid regression of neurological symptoms, which may raise doubts about the effectiveness of the selected treatment option. It is impossible to assess the potential of specific treatment without understanding the mechanisms of action of botulinum toxin and antitoxin.

AIM

AIM. This study aimed to systemise information on the mechanism underlying the damaging effect of botulinum neurotoxin, aetiological antitoxin treatment, and the patient recovery process.

DISCUSSION

DISCUSSION. The mechanism underlying the damaging effect of botulinum neurotoxin consists in the destruction of SNARE proteins in presynaptic cholinergic nerve terminals, which disrupts the release of acetylcholine into the synaptic cleft and the transmission of excitation between neurons. The lack of acetylcholine at the neuromuscular junction results in a distinctive form of persistent flaccid paralysis. The specific mechanism of action of botulinum toxin determines the treatment strategy, which includes a set of life-sustaining measures and the earliest possible antiserum administration. If used within 48 hours from the onset of symptoms, botulinum antitoxin binds botulinum toxin circulating in the blood, which stops the progression of paralysis and prevents further disorders in patients. However, botulinum antitoxin cannot neutralise the effect of the toxin that has already bound to nerve receptors, so clinical symptoms may worsen within 12 hours after antiserum administration. Restoration of normal neuronal transmission occurs through the formation of new axonal sprouts and can take a long time.

CONCLUSIONS

CONCLUSIONS. Antitoxin administration is effective and irreplaceable in the aetiological treatment of botulism. Nevertheless, the duration of recovery depends on the speed of reinnervation and restoration of transmission at the neuromuscular junction.

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The authors declare that there are no conflicts of interest present.