title: Hypermagnesemia disturbances in rats, NO-related: pentadecapeptide BPC 157 abrogates, L-NAME and L-arginine worsen.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Maria
authors.initials: M
authors.lastname: Medvidovic-Grubisic
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Vasilije
authors.initials: V
authors.lastname: Stambolija
authors.affiliation: Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Kolenc
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Katancic
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Murselovic
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Ivna
authors.initials: I
authors.lastname: Plestina-Borjan
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Strbe
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Barisic
authors.affiliation: Department of Physiology and Immunology, School of Medicine, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Sindic
authors.affiliation: Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O. Box 916, 10000, Zagreb, Croatia. sikiric@mef.hr.
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D001120:Arginine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D057809:HEK293 Cells; D006801:Humans; D008278:Magnesium Sulfate / Q000097:blood* / Q000633:toxicity*; D008297:Male; D018908:Muscle Weakness / Q000097:blood / Q000188:drug therapy; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000008:administration & dosage*; D011506:Proteins / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011506:Proteins; D009569:Nitric Oxide; D008278:Magnesium Sulfate; C083833:BPC 157; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester
keywords: BPC 157; L-Arginine; L-NAME; Magnesium; Rats