Naslov (eng)

The effects of macrophage migratory inhibitory factor and betaine on morphofunctional, cellular and tissue changes in liver fibrosis: epidemiological relevance of chronic liver disease : doctoral dissertation

Autor

Vukićević, Dušan, 1991-, 78163977

Doprinosi

Radosavljević, Tatjana, 1964-, 12671847
Maksimović, Nataša, 1974-, 12879207
Vučević, Danijela, 1969-, 12794215
Pekmezović, Tatjana, 1964-, 12668519
Gopčević, Kristina, 1960-, 12544359
Samardžić, Janko, 1980-, 14802279
Živančević Simonović, Snežana, 1960-, 12071527

Opis (srp)

Akutne i hronične bolesti jetre su rasprostranjene širom sveta sa značajnim morbiditetom i mortalitetom. Incidencija i prevalencija hroničnih bolesti jetre i njihova progresija do fibroze, ciroze i hepatocelularnog karcinoma (HCC) je veoma visoka. Od ukupno 2 miliona smrtnih slučajeva godišnje od bolesti jetre širom sveta, oko 45% svih smrtnih slučajeva uzrokovano je fibrozom jetre. Stoga je najvažniji cilj preventivnih i terapijskih strategija ublažavanje progresije bolesti od steatoze do fibroze, ciroze i HCC. S tim u vezi, na ovo ukazuje značaj brojnih eksperimentalnih modela hronične bolesti jetre, koji su dobra osnova za ispitivanje mehanizama progresije fibroze i ispitivanje antifibrogenih sredstava, a samim tim i dalje doprineti prevenciji i lečenju bolesti jetre. Fibrogeneza jetre je dinamičan i reverzibilan proces koji uključuje molekularne, ćelijske i tkivne promene odgovorne za deponovanje i remodelovanje ekstracelularnog matriksa (ECM). Oksidativni stres, inflamacija i aktivacija zvezdastih ćelija jetre (HSC) su ključni mehanizmi koji doprinose remodelovanju tkiva jetre i fibrozi. Faktor inhibicije migracije makrofaga (MIF) je multifunkcionalni citokin koji se osloba a iz imunih ćelija i igra važnu ulogu u kontroli uro enog i imunog sistema. U hroničnim bolestima jetre, inflamacija i oksidativni stres stimulišu, pored inflamatornih ćelija i endotelnie ćelije, rezidentne makrofage i hepatocite na povećanu ekspresiju MIF. Me utim, njegova uloga varira u zavisnosti od uzroka i stadijuma hronične bolesti jetre. Hepatotoksičnost izazvana tioacetamidom (TAA) je pogodan animalni model akutne i hronične bolesti jetre. Hronična primena TAA dovodi do izmenjene redoks homeostaze, inflamacije, nekroze hepatocita i fibroze jetre. Uloga MIF u oštećenju jetre izazvane TAA zavisi od interakcije brojnih faktora i signalnih puteva. MIF ispoljava svoja proinflamatorna i anti-inflamatorna dejstva u zavisnosti od etiologije i stadijuma bolesti jetre Me utim, njegova tačna uloga tokom fibrogeneze jetre nije dovoljno jasna. Betain (trimetil-glicin) je oksidativni metabolit holina koji deluje kao antioksidans povećavajući nivo S-adenozilmetionina i metionina. Upotreba betaina kao dijetetskog suplementa može ublažiti oksidativni stres i štetne efekte alkoholne i nealkoholne masne bolesti jetre, kao i fibrozu i nekrozu jetre. Me utim, precizni antioksidativni, antiinflamatorni i antifibrotični efekti betaina na MIF u nastanku i razvoju fibroze jetre još uvek nisu poznati...

Opis (eng)

Liver diseases are prevalent worldwide, causing significant morbidity and mortality. The incidence and prevalence of chronic liver disease (CLD) and its progression to fibrosis, cirrhosis and hepatocellular carcinoma (HCC) are very high. Out of a total of 2 million deaths a year from liver disease worldwide, about 45% of all deaths are caused by liver fibrosis. Therefore, the most important goal of preventive and therapeutic strategies is to alleviate the progression of the disease from steatosis to fibrosis, cirrhosis and HCC. In this regard, this is indicated by the importance of numerous experimental models of CLD that are a good basis for examining the mechanisms of fibrosis progression and testing of antifibrogenic agents, and thus further contribute to the prevention and treatment of liver disease. Hepatic fibrogenesis is a dynamic and reversible process, involving molecular, cellular, and tissue changes responsible for excess accumulation and remodeling of the extracellular matrix (ECM). Oxidative stress, inflammation and hepatic stellate cells (HSC) activation are the key mechanisms that contribute to liver tissue remodeling and fibrosis. Macrophage migration inhibition factor (MIF) is a multifunctional cytokine that is released from immune cells and contributes to the control of the innate and immune systems. In chronic liver disease, inflammation and oxidative stress stimulate, in addition to inflammatory cells and endothelial cells, resident macrophages and hepatocytes to increase MIF expression. However, its role varies depending on the cause and stage of chronic liver disease. Thioacetamide (TAA) -induced hepatotoxicity is a suitable animal model of both acute and chronic liver injury. Chronic administration of TAA leads to altered redox homeostasis, inflammation, hepatocyte necrosis, and liver fibrosis. MIF-mediated TAA-induced hepatotoxicity depends on the interaction of numerous factors and signaling pathways. MIF exhibits its proinflammatory and antiinflammatory effects depending on the etiology and stage of liver disease. However, its exact role during liver fibrogenesis is not clear enough. Betaine (trimethyl-glycine) is an oxidative metabolite of choline that acts as an antioxidant by increasing the levels of S-adenosylmethionine and methionine. The use of betaine as a dietary supplement can alleviate oxidative stress and the harmful effects of alcoholic and non-alcoholic fatty liver disease, as well as liver fibrosis and necrosis. However, the precise antioxidant, anti-inflammatory and antifibrotic effects of betaine on MIF in the onset and development of liver fibrosis are still unknown...

Opis (eng)

Medicine - Epidemiology / Medicina- Epidemiologija Datum odbrane: 08.10.2021.

Jezik

engleski

Datum

2021

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 2.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 2.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/2.0/at/legalcode

Predmet

OSNO - Opšta sistematizacija naučnih oblasti, Epidemiologija

Jetra, tioacetamid, fibrogeneza, makrofagni migratorni inhibitorni faktor, oksidativni stres, inflamacija, betain

616.36-008-092.9(043.3)

OSNO - Opšta sistematizacija naučnih oblasti, Epidemiologija

Liver, thioacetamide, macrophage migratory inhibitory factor, oxidative stress, inflammation, fibrogenesis, betaine