Uloga asimetričnog dimetilarginina (ADMA) u oksidativnom oštećenju gušterače tijekom akutne upale

doctoral thesis

• Title (english): The role of asymmetric dimethylarginine (ADMA) response to oxidative damage in acute pancreatitis
• Author: Gorana Trgo
• Mentor: Maja Radman (mentor); MBZ: 224802
• Mentor: Marijana Vučić Lovrenčić (sumentor); MBZ: 176744
• Committee member: Marijana Popović Hadžija (član povjerenstva)
• Committee member: Zoran Tadić (član povjerenstva)
• Committee member: Miljenko Solter (član povjerenstva); MBZ: 74594
• 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

Akutna upala gušterače (pankreatitis) praćena je oksidativnim i dušičnim stresom, no doprinos ovih mehanizama oštećenju tkiva i disfunkciji endokrinog dijela gušterače slabo je istražen. U ovom radu istraživana je uloga asimetričnog dimetilarginina (ADMA), endogenog inhibitora sintetaze dušičnog oksida (NOS), u razvoju oksidativno-dušičnog stresa te regulaciji glikemije na kliničkom modelu akutnog pankreatitisa. Rezultati razotkrivaju akutni pankreatitis kao stanje značajnog poremećaja glukoregulacije, pojačanog oksidativnog i dušičnog stresa te poremećene ADMA-om posredovane regulacije sinteze dušičnog oksida (NO). Hiperglikemija i oksidativno-dušični stres identificirani su kao mogući značajni uzroci smanjene bioraspoloživosti ADMA-e tijekom akutnog pankreatitisa, a intolerancija glukoze mjesec dana nakon preboljelog pankreatitisa, koja je nađena u 64% ispitanika, u izravnoj je vezi s razinom ADMA-e tijekom akutne faze bolesti. Do sada nepoznata nedostatna inhibicija sinteze NO u akutnom pankreatitisu značajno pridonosi oštećenju endokrine gušterače i kasnijem razvoju šećerne bolesti.

Abstract (english)

Acute pancreatitis is characterised by the oxidative and nitrosative stress, but contribution of these mechanisms to the tissue damage and endocrine pancreas dysfunction has been insufficiently studied. This study aimed to investigate the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric-oxide synthetase (NOS), in development of oxidative-nitrosative stress and potentially disturbed glucoregulation in the clinical model of acute pancreatitis. Results reveal acute pancreatitis as a condition associated with a significant derrangement of glucoregulation and increased oxidative-nitrosative stress, as well as a disturbed ADMAregulated nitric oxide (NO) synthesis. Both hyperglycaemia and oxidative-nitrosative stress were identified as potential significant determinants of decreased ADMA-bioavailibility during acute pancreatitis, while glucose intolerance, found in 64% of patients 1 month after acute pancreatitis, was found to be directly associated with ADMA-level during acute phase of illness. Sofar unrecognized insufficient inhibition of NO-synthesis in acute pancreatitis contributes significantly to the endocrine pancreas damage and might be responsible for subsequent development of diabetes mellitus.

• Keywords: akutni pankreatitis; dijabetes; asimetrični dimetilarginin; reaktivni kisikovi radikali; reaktivni dušikovi spojevi
• Keywords (english): acute pancreatitis; diabetes; asymmetric dymethilarginine; reactive oxygen species; reactive nitrogen species
• Language: croatian
• URN:NBN: urn:nbn:hr:217:881204
• 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: Open access
• Created on: 2017-05-18 11:50:41