High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736)

Journal of Physiology and Pharmacology

Volumn 61, Issue 2, 2010, Pages 241-250

  Ilic, S ^a   Drmic, D ^a   Zarkovic, K ^a   Kolenc, D ^a   Coric, M ^a   Brcic, L ^a   Klicek, R ^a   Radic, B ^a   Sever, M ^a   Djuzel, V ^a   Ivica, M ^a   Boban Blagaic, A ^a   Zoricic, Z ^a   Anic, T ^a   Zoricic, I ^a   Djidic, S ^a   Romic, Z ^a   Seiwerth, S ^a   Sikiric, P ^a  

^a UNIVERSITY OF ZAGREB   (Croatia)

Author keywords

Convulsions; Fatty liver; Hepatic encephalopathy; Hyperammonemia; Paracetamol; Pentadecapeptide BPC 157

Indexed keywords

ALANINE AMINOTRANSFERASE; AMMONIA; ASPARTATE AMINOTRANSFERASE; GLYCYLGLUTAMYLPROLYLPROLYLPROLYLGLYCYLLYSYLPROLYLALANYLASPARTYLASPARTYLALANYLGLYCYLLEUCYLVALINE; PARACETAMOL; PL 14736; UNCLASSIFIED DRUG; ANALGESIC AGENT; ANTIDOTE; ANTIULCER AGENT; PEPTIDE FRAGMENT; PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN DAMAGE; CHEMOPROPHYLAXIS; CONTROLLED STUDY; DRUG EFFICACY; DRUG INTOXICATION; DRUG MEGADOSE; GRAND MAL SEIZURE; HEPATIC ENCEPHALOPATHY; HYPERAMMONEMIA; LIVER INJURY; LIVER TOXICITY; MALE; NONHUMAN; RAT; ANIMAL; BRAIN; CHEMICALLY INDUCED DISORDER; DOSE RESPONSE; DRUG EFFECT; INTOXICATION; LIVER FUNCTION TEST; PATHOLOGY; SEIZURE; TIME; WISTAR RAT;

ACETAMINOPHEN; ANALGESICS, NON-NARCOTIC; ANIMALS; ANTI-ULCER AGENTS; ANTIDOTES; BRAIN; DOSE-RESPONSE RELATIONSHIP, DRUG; HEPATIC ENCEPHALOPATHY; LIVER FUNCTION TESTS; MALE; OVERDOSE; PEPTIDE FRAGMENTS; PROTEINS; RATS; RATS, WISTAR; SEIZURES; TIME FACTORS;

EID: 77955892601     PISSN: 08675910     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (41)

1. Bergman K, Muller L, Weberg Teigen S. The genotoxicity and carcinogenicity of paracetamol: a regulatory (re)view. Mut Res 1996; 349: 263-288.
2. Jaeschke H, Bajt ML. Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicol Sci 2006; 89: 31-41.
3. Fontana RJ. Acute liver failure including acetaminophen overdose. Med Clin North Am 2008; 92: 761-794, 8.
4. Nencini C, Giorgi G, Micheli L. Protective effect of silymarin on oxidative stress in rat brain Phytomedicine 2007; 14: 129-135.
5. Floyd RA. Antioxidant oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 1999; 222: 236-245.
6. Scorticati C, Prestifilippo JP, Eizayaga FX, et al. Hyperammonemia, brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication. World J Gastroenterol 2004; 10: 1321-1324.
7. Steinhauer HB, Hertting G. Lowering of the convulsive threshold by non-steroidal anti-inflammatory drugs. Eur J Pharmacol 1981; 69: 199-203.
8. Hori S, Kizu J, Kawamura M. Effects of anti-inflammatory drugs on convulsant activity of quinolones: a comparative study of drug interaction between quinolones and anti-inflammatory drugs. J Infect Chemother 2003; 9: 314-320.
9. Fetveit A. Assessment of febrile seizures in children. Eur J Pediatr 2008; 167: 17-27.
10. Wallenstein MC. Differential effects of prostaglandin synthetase inhibitors on EEG in rat. Eur J Pharmacol 1985; 111: 201-209.
11. Yohe HC, O'Hara KA, Hunt JA, Kitzmiller TJ, et al. Involvement of Toll-like receptor 4 in acetaminophen hepatotoxicity. Am J Physiol Gastrointest Liver Physiol 2006; 290: G1269-G1279.
12. Sikiric P, Petek M, Rucman R, et al. A new gastric juice peptide, BPC. An overview of the stomach-stressorganoprotection hypothesis and beneficial effects of BPC. J Physiol (Paris) 1993; 87: 313-327.
13. Sikiric P, Seiwerth S, Brcic L, et al. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response. Inflammopharmacology 2006; 14: 214-221.
14. Sikiric P, Siwerth S, Grabarevic Z, et al. The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesion induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promoters and gut peptides. Life Sci 1994; 54: 63-68.
15. Sikiric P, Seiwerth, S, Grabarevic Z, et al. The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure. Eur J Pharmacol 1997; 332: 23-33.
16. Boban Blagaic A, Blagaic V, Mirt M, et al. Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats. Eur J Pharmacol 2005; 512: 173-179.
17. Sikiric P, Marovic A, Matoz W, et al. A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine. J Physiol (Paris) 1999; 93: 505-512.
18. Jelovac N, Sikiric P, Rucman R, et al. A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidolinduced supersensitivity to amphetamine. Biol Psychiatry 1998; 43: 511-519.
19. Jelovac N, Sikiric P, Rucman R, et al. Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats. Eur J Pharmacol 1999; 379: 19-31.
20. Tohyama Y, Sikiric P, Diksic M. Effects of pentadecapeptide BPC157 on regional serotonin synthesis in the rat brain: alpha-methyl-L-tryptophan autoradiographic measurements. Life Sci 2004; 76: 345-357.
21. Blagaic AB, Blagaic V, Romic Z, Sikiric P. The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. Eur J Pharmacol 2004; 499: 285-290.
22. Tudor M, Jandric I, Marovic A, et al. Traumatic brain injury in mice and pentadecapeptide BPC 157 effect. Regul Pept 2010; 160: 26-32.
23. Boban Blagaic A, Turcic P, Blagaic V, et al. Gastric pentadecapeptide BPC 157 counteracts morphine-induced analgesia in mice. J Physiol Pharmacol 2009; 60(Suppl. 7): 177-181.
24. Veljaca M, Pavic-Sladoljev D, Mildner B, et al. Safety, tolerability and pharmacokinetics of PL 14736, a novel agent for treatment of ulcerative colitis, in healthy male volunteers. Gut 2003; 51: A309.
25. Ruenzi M, Stolte M, Veljaca M, Oreskovic K, Peterson J. Ulcerative Colitis Study Group. A multicenter, randomized, double blind, placebo-controlled phase II study of PL 14736 enema in the treatment of mild-to-moderate ulcerative colitis. Gastroenterology 2005; 128: A584.
26. Staresinic M, Petrovic I, Novinscak T, et al. Effective therapy of transected quadriceps muscle in rat: gastric pentadecapeptide BPC 157. J Orthop Res 2006; 24: 1109-1117.
27. Tkalcevic VI, Cuzic S, Brajsa K, et al. Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression. Eur J Pharmacol 2007; 570(1-3): 212-221.
28. Hrelec M, Klicek R, Brcic L, et al. Abdominal aorta anastomosis in rats and stable gastric pentadecapeptide, prophylaxis and therapy. J Physiol Pharmacol 2009; 60(Suppl. 7): 161-165.
29. Sikiric P, Seiwerth S, Grabarevic Z, et al. Hepatoprotective effect of BPC 157, a 15-amino acid peptide, on liver lesions induced by either restraint stress or bile duct and hepatic artery ligation or CCl4 administration. A comparative study with dopamine agonists and somatostatin. Life Sci 1993; 53: PL291-PL296.
30. Prkacin I, Separovic J, Aralica G, et al. Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine. J Physiol (Paris) 2001; 95: 315-324.
31. Ilic S, Brcic I, Mester M, et al. 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. J Physiol Pharmacol 2009; 60(Suppl 7): 107-114.
32. Flower RJ, Vane JR. Inhibition of prostaglandin synthetase in brain explains the antipyretic activity of acetaminophen. Nature 1972; 240: 410-411.
33. Courade JP, Besse D, Delchambrec, et al. Acetaminophen distribution in the rat central nervous system. Life Sci 2001; 69: 1455-1464.
34. Gjurasin M, Miklic P, Zupancic B, et al. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regul Pept 2010; 160: 33-41.
35. Velisek L, Veliskova J, Chudomel O, et al. Metabolic environment in substantia nigra reticulata is critical for the expression and control of hypoglycemia-induced seizures. J Neurosci 2008; 28: 9349-9362.
36. Barisic I, Seiwerth S, Sikiric P, Sindic A. BPC 157 inhibits K+ conductance in WT HEK293 cells J Physiol Pharmacol 2009; 60(Suppl. 2): 10.
37. Buttar HS, Chow AY, Downie RH. Glutathione alterations in rat liver after acute and subacute oral administration of paracetamol. Clin Exp Pharmacol Physiol 1977; 4: 1-6.
38. Konturek SJ, Brzozowski T. Gastrointestinal and liver physiology. Preface. J Physiol Pharmacol 2008; 59(Suppl 2): 3-5.
39. Brzozowski T, Konturek PC, Pajdo R, et al. Physiological mediators in nonsteroidal anti-inflammatory drugs (NSAIDs)-induced impairment of gastric mucosal defense and adaptation. Focus on nitric oxide and lipoxins. J Physiol Pharmacol 2008; 59(Suppl 2): 89-102.
40. Konturek SJ, Brzozowski T, Konturek PC, et al. Brain-gut and appetite regulating hormones in the control of gastric secretion and mucosal protection. J Physiol Pharmacol 2008; 59(Suppl 2): 7-31.
41. Sikiric P, Seiwerth S, Brcic L, et al. Revised Robert's cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications. Curr Pharm Des 2010; in press.