Oksidativni stres kot kazalnik aktivnosti kronične vnetne črevesne bolezni

Žibrat, Teja (avtor), Vovk, Tomaž (mentor), Tratenšek, Armando (komentor)

Kronična vnetna črevesna bolezen zajema Crohnovo bolezen in ulcerozni kolitis ter predstavlja kompleksno vnetno stanje, za katero so značilna obdobja aktivnosti in remisije. Trenutno razpoložljive diagnostične metode kot so endoskopija, histologija in merjenje C-reaktivnega proteina ter kalprotektina, niso vedno zadostne za celostno oceno bolezni, zato postaja iskanje dodatnih, manj invazivnih kazalnikov vse pomembnejše. Namen magistrske naloge je bil raziskati uporabnost kazalnikov oksidativnega stresa pri oceni aktivnosti kronične vnetne črevesne bolezni. V okviru prospektivne opazovalne študije smo spremljali bolnike na terapiji z različnimi biološkimi zdravili (ustekinumab, vedolizumab, infliksimab, adalimumab, golimumab) v treh časovnih točkah: ob uvedbi biološkega zdravljenja (1. obisk), med 6. in 12. tednom (2. obisk) ter med 24. in 36. tednom (3. obisk) zdravljenja z biološkim zdravilom. V raziskavo smo vključili štiri kazalnike oksidativnega stresa: proste tiole (R-SH), napredne oksidirane proteinske produkte (AOPP), malondialdehid (MDA) ter celokupno antioksidativno kapaciteto (TAC). Vrednosti R-SH, AOPP in TAC smo določili s spektrofotometričnimi metodami, MDA pa s tekočinsko kromatografijo visoke ločljivosti. Za dokazovanje povezave med koncentracijami kazalnikov in biokemičnimi kazalniki aktivnosti bolezni smo uporabili Spearmanov test korelacije. Kot drugi statistični test smo uporabili Mann-Whitney U-test, s katerim smo ugotavljali razlike v koncentracijah kazalnikov med aktivno fazo bolezni in remisijo. Aktivnost bolezni je bila opredeljena z uveljavljenimi biokemičnimi kazalniki aktivnosti bolezni (C-reaktivni protein in kalprotektin). Statistično značilne razlike smo opazili pri koncentracijah R-SH, AOPP, MDA in TAC med bolniki z aktivno boleznijo in tistimi v remisiji. Vrednosti R-SH so bile nižje (mediana [IQR]: 420 [373-464] proti 545 [447-578]), AOPP (mediana [IQR]: 161 [138-201] proti 130 [96,5-155]) in MDA (mediana [IQR]: 3,63 [2,73-4,11] proti 3,01 [2,35-3,4]) pa višje pri bolnikih z aktivno KVČB, kar odraža povečano prisotnost oksidativnega stresa. TAC je bil pri aktivni bolezni značilno znižan (mediana [IQR]: 0,98 [0,52-1,69] proti 1,76 [1,37-2,31]), pri čemer smo opazili časovno odvisno korelacijo s fekalnim kalprotektinom. Naši izsledki kažejo, da bi kazalniki oksidativnega stresa lahko bili uporabni pri ocenjevanju aktivnosti KVČB in bi potencialno lahko zmanjšali potrebo po invazivnih diagnostičnih metodah. Za potrditev njihove diagnostične vrednosti pa bi bile potrebne dodatne raziskave, ločeno za posamezna podtipa KVČB in s primerljivimi kontrolnimi skupinami.

• Jezik: Slovenski jezik
• Ključne besede: oksidativni stres, kronična vnetna črevesna bolezen, CRP, kalprotektin
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2025
• PID: 20.500.12556/RUL-174119
• Datum objave v RUL: 27.09.2025

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Oxidative stress as a marker of inflammatory bowel disease activity

Izvleček

Inflammatory bowel disease includes Crohn’s disease and ulcerative colitis and represents a complex inflammatory condition characterized by alternating periods of activity and remission. Currently available diagnostic methods, such as endoscopy, histology, and the measurement of C-reactive protein and calprotectin, are not always sufficient for a comprehensive assessment of the disease. Therefore, the search for additional, less invasive biomarkers is becoming increasingly important. The aim of this master’s thesis was to investigate the usefulness of oxidative stress markers in the assessment of inflammatory bowel disease activity. Within a prospective observational study, we monitored patients receiving biological therapy with ustekinumab, vedolizumab, infliximab, adalimumab and golimumab at three time points: at the initiation of treatment (visit 1), between weeks 6 and 12 (visit 2) and between weeks 24 and 36 of biological therapy (visit 3). Four oxidative stress markers were included in the study: free thiols (R-SH), advanced oxidation protein products (AOPP), malondialdehyde (MDA), and total antioxidant capacity (TAC). Levels of R-SH, AOPP, and TAC were determined using spectrophotometric methods, while MDA was measured by high-performance liquid chromatography. To assess the association between biomarker concentrations and biochemical indicators of disease activity, Spearman’s correlation test was used. As a second statistical approach, the Mann–Whitney U-test was used to evaluate differences in biomarker concentrations between patients in active disease and those in remission. Disease activity was defined using established biochemical markers (C-reactive protein and calprotectin). Statistically significant differences were observed in R-SH, AOPP, MDA, and TAC concentrations between patients with active disease and those in remission. R-SH levels were lower (median [IQR]: 420 [373-464] versus 545 [447-578]), while AOPP (median [IQR]: 161 [138-201] versus 130 [96,5-155]) and MDA (median [IQR]: 3,63 [2,73-4,11] versus 3,01 [2,35-3,4]) levels were higher in patients with active inflammatory bowel disease, reflecting increased oxidative stress. TAC was significantly reduced during active disease (median [IQR]: 0,98 [0,52-1,69] versus 1,76 [1,37-2,31]), with a time-dependent correlation observed with fecal calprotectin. Our results suggest that oxidative stress markers may be useful in assessing inflammatory bowel disease activity and could potentially reduce the need for invasive diagnostic methods. However, further studies are required to confirm their diagnostic value, separately for individual inflammatory bowel disease subtypes and with comparable control groups.

• Ključne besede: oxidative stress, inflammatory bowel disease, CRP, calprotectin