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Inflammopharmacology

, Volume 25, Issue 4, pp 439–449 | Cite as

Hypermagnesemia disturbances in rats, NO-related: pentadecapeptide BPC 157 abrogates, l-NAME and l-arginine worsen

  • Maria Medvidovic-Grubisic
  • Vasilije Stambolija
  • Danijela Kolenc
  • Jadranka Katancic
  • Tamara Murselovic
  • Ivna Plestina-Borjan
  • Sanja Strbe
  • Domagoj Drmic
  • Ivan Barisic
  • Aleksandra Sindic
  • Sven Seiwerth
  • Predrag SikiricEmail author
Original Article

Abstract

Aim

Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects.

Main methods

Assessment included magnesium sulfate (560 mg/kg intraperitoneally)-induced muscle weakness, muscle and brain lesions, hypermagnesemia, hyperkalaemia, increased serum enzyme values assessed in rats during and at the end of a 30-min period and medication (given intraperitoneally/kg at 15 min before magnesium) [BPC 157 (10 µg, 10 ng), l-NAME (5 mg), l-arginine (100 mg), alone and/or together]. In HEK293 cells, the increasing magnesium concentration from 1 to 5 mM could depolarize the cells at 1.75 ± 0.44 mV.

Key findings

l-NAME + magnesium-rats and l-arginine + magnesium-rats exhibited worsened severe muscle weakness and lesions, brain lesions, hypermagnesemia and serum enzymes values, with emerging hyperkalaemia. However, l-NAME + l-arginine + magnesium-rats exhibited all control values and normokalaemia. BPC 157 abrogated hypermagnesemia and counteracted all of the magnesium-induced disturbances (including those aggravated by l-NAME or l-arginine). Thus, cell depolarization due to increasing magnesium concentration was inhibited in the presence of BPC 157 (1 µM) in vitro.

Significance

BPC 157 likely counteracts the initial event leading to hypermagnesemia and the life-threatening actions after a magnesium overdose. In contrast, a worsened clinical course, higher hypermagnesemia, and emerging hyperkalaemia might cause both l-NAME and l-arginine to affect the same events adversely. These events were also opposed by BPC 157.

Keywords

BPC 157 l-Arginine l-NAME Magnesium Rats 

Notes

Acknowledgements

This research was supported by the Ministry of Science, Education and Sports, Republic of Croatia (Grant Number 108-1083570-3635).

Compliance with ethical standards

Conflict of interest

The authors indicate no potential conflicts of interest.

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Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  • Maria Medvidovic-Grubisic
    • 1
  • Vasilije Stambolija
    • 1
  • Danijela Kolenc
    • 2
  • Jadranka Katancic
    • 1
  • Tamara Murselovic
    • 1
  • Ivna Plestina-Borjan
    • 1
  • Sanja Strbe
    • 1
  • Domagoj Drmic
    • 1
  • Ivan Barisic
    • 1
  • Aleksandra Sindic
    • 3
  • Sven Seiwerth
    • 2
  • Predrag Sikiric
    • 1
    Email author
  1. 1.Department of Pharmacology, School of MedicineUniversity of ZagrebZagrebCroatia
  2. 2.Department of Pathology, School of MedicineUniversity of ZagrebZagrebCroatia
  3. 3.Department of Physiology and Immunology, School of Medicine, Croatian Institute for Brain Research, School of MedicineUniversity of ZagrebZagrebCroatia

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