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

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.

• Authors: 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 Sikiric
• Journal: Inflammopharmacology (Inflammopharmacology) Vol. 25 Issue 4 Pg. 439-449 (Aug 2017) ISSN: 1568-5608 [Electronic] Switzerland
• PMID: 28210905 (Publication Type: Journal Article)

Chemical References

• Anti-Ulcer Agents
• Enzyme Inhibitors
• Peptide Fragments
• Proteins
• Nitric Oxide
• Magnesium Sulfate
• BPC 157
• Arginine
• NG-Nitroarginine Methyl Ester

Topics

• Amino Acid Sequence
• Animals
• Anti-Ulcer Agents (administration & dosage)
• Arginine (administration & dosage)
• Drug Therapy, Combination
• Enzyme Inhibitors (administration & dosage)
• HEK293 Cells
• Humans
• Magnesium Sulfate (blood, toxicity)
• Male
• Muscle Weakness (blood, drug therapy)
• NG-Nitroarginine Methyl Ester (administration & dosage)
• Nitric Oxide (antagonists & inhibitors)
• Peptide Fragments (administration & dosage)
• Proteins (administration & dosage)
• Rats
• Rats, Wistar