Sistematični pregled in metaanaliza kazalnikov oksidativnega stresa pri kronični vnetni črevesni bolezni

Aberšek, Nina (author), Vovk, Tomaž (mentor), Drobne, David (co-mentor)

Kronična vnetna črevesna bolezen (KVČB) je bolezen prebavil, pri kateri se izmenjavajo aktivne faze in obdobja remisije. Mehanizem nastanka še ni znan, zato na tem področju potekajo številne raziskave, ki so prinesle boljše poznavanje patogeneze in zdravljenja, na področju diagnostike pa je še prostor za izboljšave. Zlati diagnostični standard ostaja endoskopija, ki je zaradi invazivnosti neprijetna za bolnike. Študije kažejo, da oksidativni stres prispeva k razvoju in napredovanju KVČB, zato smo se v magistrski nalogi odločili preučiti, s katerim kazalnikom oksidativnega stresa bi lahko razlikovali med aktivno fazo bolezni in remisijo. V ta namen smo naredili sistematični pregled literature in meta-analizo. V sistematični pregled literature smo vključili 59 člankov na osnovi vključitvenih in izključitvenih kriterijev. Ocenili smo pristranost v meta-analizi uporabljenih 46 člankov. Rezultati so pokazali, da ima 26 raziskav nizko, 10 raziskav srednje in 10 raziskav visoko tveganje za pristranost. Meta-analizo smo izvedli v programu Review Manager 5.4., rezultate prikazali v obliki drevesnih diagramov, velikost učinka pa izrazili kot standardizirano povprečno razliko (SMD) med bolniki in zdravimi. Glede na zdrave so bili statistično značilno povišani (SMD): napredni oksidirani proteinski produkti (AOPP) (1,81), malonildialdehid in s tiobarbiturno kislino reagirajoče snovi (0,87) ter glutation peroksidaza (0,67). Kazalniki, ki so bili glede na zdrave statistično značilno znižani so: glutation (-1,56), celokupni status antioksidantov in celokupna kapaciteta antioksidantov (-1,32), albumin (-1,29), bilirubin (-1,09), vitamin A (-0,86), transferin (-0,75), prosti tioli (-0,69), vitamin C (-0,66) ter vitamin E (-0,41). Dodatno so bili bilirubin (v aktivni fazi -3,10, v remisiji -0,78), katalaza (CAT) (v aktivni fazi -0,68, v remisiji -0,10) in transferin (v aktivni fazi -1,17, v remisiji -0,33) statistično pomembno znižani glede na SMD pri bolnikih v aktivni fazi in remisiji. Vrednost SMD za AOPP pa je bila pri aktivni fazi (3,59) statistično pomembno povišana glede na remisijo (0,89). Pri izvedbi občutljivostne analize z izključitvijo raziskav z visokim tveganjem za pristranost nismo opazili statistično značilne spremembe velikosti učinka za noben kazalnik. Potrebne bodo nadaljnje študije, ki bodo pokazale, kako točno je oksidativni stres vpleten v KVČB. Meritve koncentracij oz. aktivnosti bilirubina, AOPP, CAT in transferina bi lahko pripomogle k obvladovanju in diagnostiki KVČB, saj lahko z njimi hitreje in manj invazivno zaznavamo vnetne procese.

• Language: Slovenian
• Keywords: kronična vnetna črevesna bolezen, oksidativni stres, oksidativne poškodbe, antioksidanti, meta-analiza
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-137846
• Publication date in RUL: 03.07.2022

Secondary language

• Language: English
• Title: Systematic review and meta-analysis of oxidative stress markers in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a gastrointestinal disease, characterized by episodes of active and inactive phases. Many studies are ongoing as the mechanism of disease progression is still unknown. Studies contributed to better knowledge of pathogenesis and treatment but there is still space for improvements in diagnostics. Endoscopy is the main diagnostic standard which is unpleasant for patients due to its invasiveness. Studies show that oxidative stress contributes to the development and progression of IBD, therefore the goal of this master’s thesis was to determine markers of oxidative stress which could help distinguish between active and inactive phase of IBD. For this purpose, a systematic literature review and meta-analysis were carried out. Systematic review included 59 articles based on inclusion and exclusion criteria. The 46 articles included in the meta-analysis were assessed for risk of bias. 26 articles were of good, 10 articles of fair and 10 articles of poor quality in terms of risk of bias. Meta-analysis was carried out with Review Manager 5.4., results were presented through forest plots and the size effect were in form of standardized mean difference (SMD) between patients and healthy controls. Concentration or activity was significant increased by IBD patients compared to healthy controls for next markers (SMD): advanced oxidation protein products (AOPP) (1,81), malondialdehyde and thiobarbituric acid reactive substances (0,87) and glutathione peroxidase (0,67). Concentration or activity was significant decreased by IBD patients compared to healthy controls for glutathione (-1,56), total antioxidant capacity and total antioxidant status (-1,32), albumin (-1,29), bilirubin (-1,09), vitamin A (-0,86), transferrin (-0,75), free thiols (-0,69), vitamin C (-0,66) and vitamin E (-0,41). Additionally, were bilirubin (in active phase -3,10, in inactive phase -0,78), catalase (CAT) (in active phase -0,68, in inactive phase -0,10) and transferrin (in active phase -1,17, in inactive phase -0,33) significant decreased according to SMD by active compared to inactive IBD. SMD value for AOPP was statistically increased by active (3,59) compared to inactive IBD (0,89). Using a sensitivity analysis with excluded high risk of bias articles we did not observe a statistically relevant change in the overall effect for any of the markers. Further studies are needed to point out how oxidative stress is involved in IBD and its contribution to pathogenesis. Measurements of concentration or activity of bilirubin, CAT, transferrin and AOPP could contribute to control and diagnostics of IBD as measurements of markers are faster and less invasive detection of inflammatory processes.

• Keywords: inflammatory bowel disease, oxidative stress, oxidative damage, antioxidants, meta-analysis