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BPC 157 antagonized the general anaesthetic potency of thiopental and reduced prolongation of anaesthesia induced by l-NAME/thiopental combination

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Abstract

Aim

We hypothesized that certain effects of the general anaesthetic thiopental are dependent on NO-related mechanisms, which were consequently counteracted by stable gastric pentadecapeptide BPC 157.

Main methods

(1) All rats intraperitoneally received thiopental (20, 30, 40, and 50 mg/kg) while medication BPC 157 (10 μg/kg, 10 ng/kg, and 10 pg/kg) was given intraperitoneally at 5 min before thiopental. (2) To determine NO-related mechanisms, all rats received intraperitoneally thiopental 40 mg/kg while BPC 157 (10 μg/kg), l-NAME (10 mg/kg) and l-arginine (30 mg/kg) were applied alone and/or combined. BPC 157 was given at 25 min before thiopental while l-NAME, l-arginine, alone and/or combined, were applied at 20 min before thiopental.

Key findings

(1) BPC 157 own effect on thiopental anaesthesia: BPC 157 (10 ng/kg and 10 μg/kg) caused a significant antagonism of general anaesthesia produced by thiopental with a parallel shift of the dose–response curve to the right. (2) l-NAME-l-arginine-BPC 157 interrelations: l -NAME: Thiopental-induced anaesthesia duration was tripled. l-arginine: Usual thiopental anaesthesia time was not influenced. Active only when given with l-NAME or BPC 157: potentiating effects of l-NAME were lessened, not abolished; shortening effect of BPC 157: abolished. BPC 157 and l -NAME: Potentiating effects of l-NAME were abolished. BPC 157 and l -NAME and l-arginine: BPC 157 +l-NAME +l-arginine rats exhibited values close to those in BPC 157 rats.

Significance

Thiopental general anaesthesia is simultaneously manipulated in both ways with NO system activity modulation, l-NAME (prolongation) and BPC 157 (shortening/counteraction) and l-arginine (interference with l-NAME and BPC 157).

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Acknowledgements

This research was supported from Ministry of Science, Education and Sports, Republic of Croatia (Grant No. 108-1083570-3635).

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, PO Box 916, 10000, Zagreb, Croatia

    Mladen Zemba, Andrea Zemba Cilic, Igor Balenovic, Matija Cilic, Bozo Radic, Jelena Suran, Domagoj Drmic, Antonio Kokot, Vasilije Stambolija, Tamara Murselovic, Jadranka Katancic Holjevac, Sandra Uzun, Viktor Djuzel, Josipa Vlainic & Predrag Sikiric

  2. Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia

    Sven Seiwerth

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  1. Mladen Zemba
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Zemba, M., Cilic, A.Z., Balenovic, I. et al. BPC 157 antagonized the general anaesthetic potency of thiopental and reduced prolongation of anaesthesia induced by l-NAME/thiopental combination. Inflammopharmacol 23, 329–336 (2015). https://doi.org/10.1007/s10787-015-0249-9

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