Učinkovitost suplementacije alfa-lipoičnom kiselinom kod premalignih promjena vrata maternice

doctoral thesis

• Title (english): The efficiency of supplementation with alpha-lipoic acid in patients with precancerous cervical lesions
• Author: Anja Divković
• Mentor: Dubravka Vitali Čepo (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Alan Šerman (član povjerenstva)
• Committee member: Dunja Rogić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of food chemistry); Zagreb
• Defense date and country: 2024-09-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Premaligne lezije vrata maternice etiološki su vezane uz infekciju humanim papiloma virusom
(HPV) i posljedičan razvoj upale i oksidativnog stresa zbog čega bi se antioksidansi mogli
smatrati učinkovitim protiv progresije skvamozne intraepitelne lezije niskog stupnja (engl. low
grade SIL, LSIL). Recentna istraživanja pokazuju da je α-lipoična kiselina (ALA) jedan od
najpotentnijih prirodnih antioksidanasa s još uvijek ograničenom terapijskom primjenom u
liječenju bolesti povezanih s upalom i oksidativnim stresom. Cilj ove randomizirane, dvostruko
slijepe placebom kontrolirane studije je istražiti učinkovitost suplementacije ALA-om (600
mg/dne) na regresiju LSIL-a na uzorku od 100 pacijentica te dobiti širi uvid u terapijski
potencijal i mehanizme djelovanja ALA-e na oksidativni stres, upalne biljege i parametre
lipidnog statusa. Prisutnost LSIL-a utvrđena je nakon citološkog probira, kolposkopskog
pregleda i ciljane biopsije te histološke potvrde citološko-kolposkopske dijagnoze. Parametri
oksidativnog stresa, upale, lipidnog statusa i prisustvo HPV-a su utvrđeni standardnim
laboratorijskim metodama. Prehrambene i životne navike istražene su korištenjem
standardiziranog i validiranog semikvantitativnog upitnika o konzumiranju hrane i pića (engl.
Food Frequency Questionnaire, FFQ). Dobiveni rezultati pokazali su da je suplementacija
ALA-om znatno reducirala broj pacijentica s citološkim abnormalnostima niskog stupnja u
odnosu na pacijentice koje su uzimale placebo. Uzimajući u obzir dobivenu razinu značajnosti
(p < 0,001), prezentirani rezultati upućuju da kratkoročna suplementacija ALA-om pokazuje
klinički značajan učinak na cervikalnu citologiju. Intervencija nije imala značajan utjecaj na
parametre antioksidativnog statusa iako je antioksidativni kapacitet seruma (Trolox
ekvivalentni antioksidativni učinak (engl. Trolox equivalent antioxidant capacity, TEAC),
kapacitet vezanja kisikovih radikala (engl. Oxygen Radical Absorbance Capacity, ORAC) i
Folin-Ciocalteu redukcijski potencijal (engl. Folin-Ciocalteu, FC)) bio povećan nakon
suplementacije kod određenih podskupina pacijentica u ovisnosti o njihovom unosu
antioksidanasa hranom. Utjecaj suplementacije ALA-om na lipemiju ovisio je o inicijalnom
lipidnom statusu pacijentica. Buduće studije bi trebale biti usmjerene na istraživanje
učinkovitosti dugoročnije terapije ALA-om (duže od 3 mjeseca) te uključiti i pacijentice s
visokim stupnjem SIL-a. Također bi se trebale usmjeriti na istraživanje inovativnih formulacija
ALA-e s povećanom bioraspoloživošću, te na istraživanje sinergističkih učinaka modificiranog
životnog stila i suplementacije ALA-om.

Abstract (english)

Precancerous lesions of the cervix are etiologically related to human papilloma virus (HPV)
infection and consequential development of inflammation and oxidative stress, which is why
antioxidants might be considered effective against progression of low-grade squamous
intraepithelial lesion (LSIL). Recent investigations show that α-lipoic acid (ALA) is one of the
most potent natural antioxidants with (still) limited therapeutic application in treatment of
diseases related to inflammation and oxidative stress. This randomized, double-blind, placebocontrolled
study aimed to investigate the effectiveness of ALA supplementation (600 mg/day)
on the regression of LSIL in a sample of 100 patients and to gain a broader insight into
therapeutic potential and mechanisms of action of ALA on oxidative stress, inflammatory
markers and lipid status parameters. The presence of LSIL was determined after the cytological
screening, colposcopic examination and targeted biopsy, as well as histological confirmation
of cytological-colposcopic diagnosis. Parameters of oxidative stress, inflammation, lipid status
and the presence of HPV were determined by standard laboratory methods. Dietary and lifestyle
habits were investigated using a standardized and validated semi-quantitative food
questionnaire (FFQ). Obtained results showed that ALA supplementation significantly reduced
the proportion of patients with low-grade cytological abnormalities, in comparison to placebo.
Given the obtained level of significance (p < 0.001), the presented results indicate that shortterm
ALA supplementation shows a clinically significant effect on cervical cytology.
Intervention did not have a significant influence on oxidative stress parameters although certain
indicators of antioxidant status were increased after supplementation in particular subgroups of
patients, depending on their dietary antioxidant intake. Influence of ALA supplementation on
lipemia depended on initial lipid status of patients. Future studies should focus on the
investigation of effectiveness of long-term therapies (> 3 months) and also include patients with
high-grade SIL; investigation of innovative formulations of ALA that might induce
bioavailability and the investigation of synergistic effects of lifestyle modifications and ALA
supplementation.

• Keywords: skvamozna intraepitelna lezija niskog stupnja; humani papiloma virus; HPV; α-lipoična kiselina; ALA; parametri antioksidativnog statusa; parametri upale; parametri lipidnog statusa; indeks kvalitete prehrane
• Keywords (english): low-grade squamous intraepithelial lesion; LSIL; human papilloma virus; HPV; α-lipoic acid; ALA; oxidative stress parameters; inflammatory markers; lipid status parameters; diet quality index
• Language: croatian
• URN:NBN: urn:nbn:hr:163:277535
• Promotion: 2024
• Study programme: Title: Pharmceutical-biochemical sciences - doctoral study - university study; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti u području biomedicine i zdravstva (doktor/doktorica znanosti u području biomedicine i zdravstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-10-08 08:41:56