Over-dose insulin and stable gastric pentadecapeptide BPC 157. Attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, fatty liver, breakdown of liver glycogen, profound hypoglycemia and calcification in rats.
We focused on over-dose insulin (250 IU/kg i.p.) induced gastric ulcers and then on other disturbances that were concomitantly induced in rats, seizures (eventually fatal), severely damaged neurons in cerebral cortex and hippocampus, hepatomegaly, fatty liver, increased AST, ALT and amylase serum values, breakdown of liver glycogen with profound hypoglycemia and calcification development. Calcium deposits were present in the blood vessel walls, hepatocytes surrounding blood vessels and sometimes even in parenchyma of the liver mainly as linear and only occasionally as granular accumulation. As an antidote after insulin, we applied the stable gastric pentadecapeptide BPC 157 (10 microg/kg) given (i) intraperitoneally or (ii) intragastrically immediately after insulin. Controls received simultaneously an equivolume of saline (5 ml/kg). Those rats that survived till the 180 minutes after over-dose application were further assessed. Interestingly, pentadecapeptide BPC 157, as an antiulcer peptide, may besides stomach ulcer consistently counteract all insulin disturbances and fatal outcome. BPC 157 rats showed no fatal outcome, they were mostly without hypoglycemic seizures with apparently higher blood glucose levels (glycogen was still present in hepatocytes), less liver pathology (i.e., normal liver weight, less fatty liver), decreased ALT, AST and amylase serum values, markedly less damaged neurons in brain and they only occasionally had small gastric lesions. BPC 157 rats exhibited mostly only dot-like calcium presentation. In conclusion, the success of BPC 157 therapy may indicate a likely role of BPC 157 in insulin controlling and BPC 157 may influence one or more causative process(es) after excessive insulin application.
Ilic
S
S
Department of Pharmacology and Pathology Medical Faculty University of Zagreb, Zagreb, Croatia.
Brcic
I
I
Mester
M
M
Filipovic
M
M
Sever
M
M
Klicek
R
R
Barisic
I
I
Radic
B
B
Zoricic
Z
Z
Bilic
V
V
Berkopic
L
L
Brcic
L
L
Kolenc
D
D
Romic
Z
Z
Pazanin
L
L
Seiwerth
S
S
Sikiric
P
P
D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002114:Calcinosis / Q000139:chemically induced / Q000517:prevention & control; D062787:Drug Overdose / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006003:Glycogen / Q000378:metabolism; D006529:Hepatomegaly / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000633:toxicity*; D007328:Insulin / Q000633:toxicity*; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D011506:Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology / Q000517:prevention & control; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D000897:Anti-Ulcer Agents; D000931:Antidotes; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D011506:Proteins; C083833:BPC 157; D006003:Glycogen