Biološki učinci D-izomera metencefalina u eksperimentalnom modelu kemijskog oštećenja jetre miša paracetamolom

doctoral thesis

• Title (english): Biological effects of D- met-enkephalin isomer in a murine model of chemical liver injury induced by paracetamol
• Author: Roko Martinić
• Mentor: Nikola Štambuk (mentor); MBZ: 160463
• Committee member: Mirko Hadžija (član povjerenstva); MBZ: 15065
• Committee member: Gordana Lacković-Venturin (član povjerenstva)
• Committee member: Ranko Stojković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2014, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Peptidi i proteini u sisavaca i viših organizama građeni su od L-amino kiselina. Istraživanja peptida-enantiomera i upotreba D-amino kiselina je važan postupak za pripravu novih proteinskih struktura s različitim svojstvima u odnosu na nativne L-oblike. L-met-encefalin enantiomer posjeduje hepatoprotektivne odlike u mišjem modelu hepatotoksičnosti inducirane paracetamolom. Trenutno nema dostupnih podataka o osobinama i biološkim učincima Dmet- encefalin enantiomera, te je svrha ovog rada istražiti njegov hepatoprotektivni potencijal. D-enantiomer pokazao je zaštitni učinak u rasponu doza od 0,5 mg/kg do 20 mg/kg. Plazmatske aktivnosti enzima alanin aminotransferaza i aspartat aminotransferaza te nekroza jetre bile su značajno smanjene u usporedbi s kontrolnim životinjama koje su tretirane fiziološkom otopinom (p<0,01). Najjači potektivni učinak je uočen u životinja tretiranih s dozom od 5 mg/kg. Učinci su također ispitani u uvjetima blokade receptora i peptida. Pokazano je da su vjerojatno posredovani putem ζ i δ opioidnih receptora, a blokira ih naltrekson i antisens peptid IPPKY. Zaključeno je da su protektivni učinci D-met-encefalina usporedivi s učincima L-met-encefalina.

Abstract (english)

Peptides and proteins in mammals and higher organisms are composed of L-amino acids. The investigation of peptide-enantiomerism and the use of D-amino acids is important for the design of novel protein structures, with properties different from the native all L-forms. Lmet- enkephalin enantiomer exhibits strong protection in the mice model of acetaminophen induced hepatotoxicity. Howerver, there is currently no data available on the properties and biological effects of D-met-enkephalin enantiomer, and consequently we evaluated its hepatoprotective potential. D-enantiomer was shown to be protective in the dose range from 0.5 mg/kg to 20 mg/kg. Plasma AST, ALT and liver necrosis were significantly reduced in comparison to control animals treated with physiological saline (p>0.01). The best protection was observed in animals treated with a dose of 5 mg/kg. The effects of D-met-enkephalin were investigated from the standpoint of the receptor and peptide blockade. It was shown that they were probably mediated via δ and ζ opioid receptors, and blocked by naltrexone and antisense peptide. It is concluded that D-met-enkephalin induced hepatoprotection is comparable to L-met-enkephalin one.

• Keywords: D-met-encefalin; naltrekson; opioidni receptori; antisens peptidi; enantiomeri; paracetamol; hepatoprotekcija
• Keywords (english): D-met-enkephalin; naltrexone; opioid receptors; antisense peptidies; enantiomers; paracetamol; hepatoprotection
• Language: croatian
• URN:NBN: urn:nbn:hr:217:257223
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-05-18 10:16:46