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Lozic, Marin; Stambolija, Vasilije; Kovacevic, Josip; Zivanovic‐Posilovic, Gordana; Suran, Jelena; Duplancic, Bozidar; Mirkovic, Ivan; Kokot, Antonio; Drmic, Domagoj; Seiwerth, Sven; Sikiric, Predrag
The FASEB journal, April 2019, 2019-04-00, Letnik: 33, Številka: S1Journal Article
We documented that the stable gastric pentadecapeptide BPC 157 antagonized local anaesthetic effect of lidocaine. BPC 157 (LD1 not achieved) was implemented as an anti‐ulcer peptide in inflammatory bowel disease trials and now in a multiple sclerosis trial (Curr Pharm Des. 2018;24(18):1990–2001). Stable gastric pentadecapeptide BPC 157 was previously shown as a cardioprotective compound in a model of arrhythmia induced by bupivacaine toxicity where it counteracts arrhythmias and prevents lethal outcome (Eur J Pharmacol. 2016 Dec 15;793:56–65) much like in other cardiotoxicity mainly related to potassium disturbances, both hyperkalemia and hypokalemia, in vivo and in vitro (HEK293 cells) (Curr Pharm Des. 2018;24(18):1990–2001). We used Wistar Albino male rats, underwent regional blocks with lidocaine (spinal intrathecal block (lidocaine 6 mg/kg, 0.1 ml/rat, 550 g b.w.) or axillary block (lidocaine 15 mg/kg, 0.3 ml/rat, 220 g b.w.). Rats received BPC 157 (10 μg, 10 ng, 10 pg/kg intraperitoneally or intragastrically) or an equivolume of saline (5 ml/kg), either immediately or at 10 min when local anesthesia was fully established. Consistently, while lidocaine application produced a prolong function failure, all BPC 157 regimens significantly shortened time to full function recovery, either given immediately after lidocaine application or later, in the conditions of full local anesthesia. In other experiments, using a hot plate (55°C for 3 minutes) when rat hind paws were infiltrated with 2% lidocaine (0.1 ml/paw), a subsequent infiltration with BPC 157 (10 μg, 10 ng, 10 pg/kg) results in the faster feet lifting and much less edema (Figure 1). Finally, ECG recording documented that the mentioned regimens of BPC 157 markedly counteracted the lidocaine‐induced arrhythmias as well. Therefore, it may be possible that pentadecapeptide BPC 157 acts as the missing antidote to local anesthethics, and potentially deleterious and even life threatening adverse effects of toxic doses of local anesthethics would be markedly attenuated or even abolished. Support or Funding Information This work was supported by the University of Zagreb scientific support fund grant number BM099. This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
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