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Stable gastric pentadecapeptide BPC 157 and bupivacaine


Živanović-Posilović, Gordana; Balenović, Diana; Barišić, Ivan; Strinić, Dean; Stambolija, Vasilije; Udovičić, Mario; Uzun, Sandra; Drmić, Domagoj; Vlainić, Josipa; Lovrić Benčić, Martina et al.
Stable gastric pentadecapeptide BPC 157 and bupivacaine // European journal of pharmacology, 793 (2016), 56-65 doi:10.1016/j.ejphar.2016.10.035 (međunarodna recenzija, članak, znanstveni)


Naslov
Stable gastric pentadecapeptide BPC 157 and bupivacaine

Autori
Živanović-Posilović, Gordana ; Balenović, Diana ; Barišić, Ivan ; Strinić, Dean ; Stambolija, Vasilije ; Udovičić, Mario ; Uzun, Sandra ; Drmić, Domagoj ; Vlainić, Josipa ; Lovrić Benčić, Martina ; Sindić, Aleksandra ; Seiwerth, Sven ; Sikirić, Predrag

Izvornik
European journal of pharmacology (0014-2999) 793 (2016); 56-65

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
BPC 157 ; Bupivacaine ; Cardiotoxicity ; Rats ; HEK293 cell depolarization

Sažetak
Bupivacaine toxicity following accidental overdose still lacks therapeutic solution. However, there are major arguments for testing BPC 157 against bupivacaine toxicity in vivo in rats, in particular, and then finally, in vitro. These are: the lack of any known BPC 157 toxicity, a lifesaving effect via the mitigation of arrhythmias in rats underwent hyperkalemia or digitalis toxicity, the elimination of hyperkalemia and arrhythmias in rats underwent succinylcholine toxicity and finally, the reduction of potassium-induced depolarization in vitro (in HEK293 cells) in severe hyperkalemia. Most importantly, BPC 157 successfully prevents and counteracts bupivacaine cardiotoxicity ; BPC 157 is effective even against the worst outcomes such as a severely prolonged QRS complex. Here, rats injected with bupivacaine (100 mg/kg IP) exhibited bradycardia, AV-block, ventricular ectopies, ventricular tachycardia, T-wave elevation and asystole. All of the fatalities had developed T-wave elevation, high-degree AV-block, respiratory arrest and asystole. These were largely counteracted by BPC 157 administration (50 mu g/kg, 10 mu g/kg, 10 ng/kg, or 10 pg/kg IP) given 30 min before or 1 min after the bupivacaine injection. When BPC 157 was given 6 min after bupivacaine administration, and after the development of prolonged QRS intervals (20 ms), the fatal outcome was markedly postponed. Additionally, the effect of bupivacaine on cell membrane depolarization was explored by measuring membrane voltages (Vm) in HEK293 cells. Bupivacaine (1 mM) alone caused depolarization of the cells, while in combination with BPC 157 (1 mu m), the bupivacaine-induced depolarization was inhibited. Together, these findings suggest that the stable gastric pentadecapeptide BPC 157 should be a potential antidote for bupivacaine cardiotoxicity.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
108-1083570-3635 - Pentadekapeptid BPC 157 - daljnja istraživanja (Predrag Sikirić, )

Ustanove
Institut "Ruđer Bošković", Zagreb,
Medicinski fakultet, Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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