Inhibition of ABCB1 activity in cerebrovascular disease may increase pharmacotherapy effectiveness

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Abstract

Introduction. Despite the development of numerous drugs with neuroprotective activity, their efficacy in cerebrovascular disease remains low, which may partly be due to the efflux function of protein ABCB1 and insufficient penetration of the blood-brain barrier by these drugs.

Aim — to evaluate the potential to inhibit ABCB1 functional activity in the blood-brain barrier to improve the efficacy of neuroprotective therapy against brain ischemia.

Materials and methods. An experimental study was performed on 60 adult male Wistar rats split up into 5 groups: group 1 with falsely operated animals; group 2 with rats with modeled cerebral ischemia using bilateral ligation of the common carotid arteries and preliminary intravenous injection of saline (control ischemia); group 3 with animals that were intravenously administered a neuroprotective agent, an АВСВ1 substrate (nimodipine), 30 min before arterial ligation; group 4 with rats that were intravenously administered an АВСВ1 inhibitor (omeprazole) 30 minutes before disease modeling; and group 5 with animals with ischemia that were intravenously administered nimodipine together with omeprazole before the operation. The efficacy of the tested substances was based on a reduction in animal deaths and the severity of neurological deficits 4, 12, 24, 48, and 72 hours after pathology modeling.

Results. The combination of nimodipine and omeprazole increased rat survival after ischemia modeling and decreased neurological deficits compared with the control rats with cerebral ischemia and the rats administered a neuroprotective agent.

Conclusion. The combination of a neuroprotective agent (ABCB1 substrate) and a transporter inhibitor provides an effective approach to improve the efficacy of neuroprotective pharmacotherapy in cerebral ischemia.

About the authors

Ivan V. Chernykh

Ryazan State Medical University

Author for correspondence.
Email: ivchernykh88@mail.ru
Russian Federation, Ryazan

Aleksey V. Shchulkin

Ryazan State Medical University

Email: ivchernykh88@mail.ru
Russian Federation, Ryazan

Sergei K. Pravkin

Ryazan State Medical University

Email: ivchernykh88@mail.ru
Russian Federation, Ryazan

Maria V. Gatsanoga

Ryazan State Medical University

Email: ivchernykh88@mail.ru
Russian Federation, Ryazan

Elena N. Yakusheva

Ryazan State Medical University

Email: ivchernykh88@mail.ru
Russian Federation, Ryazan

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Copyright (c) 2021 Chernykh I.V., Shchulkin A.V., Pravkin S.K., Gatsanoga M.V., Yakusheva E.N.

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