Terapijska vrijednost N-acetilcisteina u liječenju virusnih akutnih respiratornih infekcija

master's thesis

• Title (english): Therapeutic value of N-acetylcysteine in the treatment of viral acute respiratory infections
• Author: Petar Musa
• Mentor: Robert Likić (mentor)
• Committee member: Jasenka Markeljević (predsjednik povjerenstva)
• Committee member: Marko Jakopović (član povjerenstva)
• Committee member: Robert Likić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2023-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

N-acetilcistein (NAC) stari je lijek koji se koristi i ispituje u liječenju brojnih bolesti i stanja, a izmeĎu ostaloga i u liječenju virusnih akutnih respiratornih infekcija. Prolazi kroz opseţan metabolizam prvoga prolaska te ima nisku oralnu bioraspoloţivost. Opseţno se veţe za plazmatske bjelančevine, a udio doze koji se neizmijenjen izluči urinom je malen. Iako prvotno namijenjen kao mukolitik, pokazuje antioksidativna, citoprotektivna i antivirusna svojstva. Davatelj je sumporovodika (H2S), odnosno povisuje unutarstanične razine H2S-a te preko njega ostvaruje svoje djelovanje stvarajući sulfanske sumporne spojeve. U istraţivanjima na kulturama stanica NAC je smanjio stvaranje kisikovih radikala i utjecao na aktivaciju transkripcijskih čimbenika, poput Nrf2, NF-κB i IRF3. N-acetilcistein je tako djelovao kao imunomodulator, smanjujući lučenje proupalnih citokina, smanjujući kemotaksiju leukocita i potičući funkciju regulacijskih limfocita T, a uz to je ometao virusno umnaţanje te je inhibirao apoptozu, promičući stanično preţivljenje. Siguran je za populaciju stariju od dvije godine i dobro se tolerira, čak i pri visokim dozama. Ispitivanja na ţivotinjama uglavnom pokazuju njegove povoljne učinke. Klinička ispitivanja, iako ukazuju na moguću korist NAC-a, pogotovo u liječenju blaţih oblika upale pluća te u prevenciji akutnih infekcija gornjega respiratornog sustava, zasada ne daju konačan odgovor. Manjak je kvalitetnih istraţivanja s velikim uzorcima koja bi nepobitno pokazala njegovu djelotvornost. Potrebna su daljnja istraţivanja da bi se ustvrdila vrijednost NAC-a u liječenju virusnih akutnih respiratornih infekcija.

Abstract (english)

N-acetylcysteine (NAC) is an old drug that is used and studied in the treatment of many condition and illnesses, some of which are viral acute respiratory infections. It undergoes extensive first-pass metabolism and has a low oral bioavailability. It binds extensively to plasma proteins and the fraction of the dose excreted unchanged into urine is small. Tough initially intended as a mucolytic, it shows antioxidant, cytoprotective and antiviral properties. It is a hydrogen sulfide (H2S) donor, that is, it raises intracellular H2S levels by which it exerts its effects through the creation of sulfane sulfur species. In cell culture studies, NAC reduced reactive oxygen species generation and affected the activation of trascription factors, such as Nrf2, NF-κB and IRF3. It acted as an immunomodulator by reducing proinflammatory cytokine excretion, reducing leukocyte chemotaxis, and promoting the function of regulatory T lymphocytes. It also inhibited viral replication and apoptosis, promoting cell survival. It is safe in a population older than two years of age and is well tolerated, even at high doses. Trials on animals mostly show its benefitial effects. Clinical trials, altough they indicate its possible use, especially in the treatment of milder forms of pneumonia and prevention of acute infections of the upper respiratory system, as of yet don't give a definitive answer. There is a lack of good quality studies with large samples that would undeniably show its effectiveness. Further research is needed to establish NAC's value in the treatment of viral acute respiratory infections.

• Keywords: N-acetilcistein; virusna infekcija; COVID-19; farmakokinetika; sumporovodik
• Keywords (english): N-acetylcysteine; viral infection; COVID-19; pharmacokinetics; hydrogen sulfide
• Language: croatian
• URN:NBN: urn:nbn:hr:105:758738
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-10-26 12:56:24