Naslov (srp)

Ispitivanje imunomodulatornih, antioksidativnih i antiapoptotičkih efekata melatonina tokom endotoksemije izazvane lipopolisaharidom: eksperimentalna studija

Autor

Sokolović, Danka,

Doprinosi

Lazarević, Milan, 1983-
Džopalić, Tanja, 1980-
Marjanović, Goran, 1969
Vučetić, Dušan, 1961

Opis (srp)

Sepsis is damage to multiple organs, which is caused by anextreme inflammatory response of the host to the infection. Themost well-known molecule of microorganisms that cause aninflammatory reaction during sepsis is lipopolysaccharide (LPS),also known as endotoxin, which forms the cell wall of gramnegativebacteria. Through its contact with the Toll-like receptor 4of immune cells, it causes the activation of intracellular cascades,the translocation of NF-κB into the nucleus, which increases theexpression of genes encoding pro-inflammatory cytokines.Melatonin is a hormone synthesized in the pineal gland, it is aregulator of the circadian rhythm and has significant antioxidantand anti-inflammatory effects.The aim of the research within the doctoral dissertation isto examine the immunomodulatory, antioxidant and antiapoptoticeffects of melatonin during endotoxemia caused by Escherichiacoli lipopolysaccharide.During experimental endotoxemia caused by LPS, therewas an increase in the number of neutrophils, a decrease in thenumber of lymphocytes (due to their massive apoptosis), anincrease in the neutrophil-lymphocyte ratio and thrombocytopenia(due to increased consumption of platelets), all of which indicate astate of sepsis. Administering melatonin during endotoxemianormalizes the number of lymphocytes, as well as the ratio ofneutrophils and lymphocytes. Endotoxemia in the liver tissue ledto an increase in the level of NF-κB and pro-inflammatorycytokines (TNF-α and IL-6), more intense oxidative stress (byincreasing lipid peroxidation, decreasing the level of reducedglutathione and decreasing antioxidant defense enzymes),increasing the content of Nrf-2 protein, as well as more intensiveapoptosis (by increasing the activity of DNase and caspase-3).Also, during endotoxemia, there was an increase in the level ofnitric oxide in the liver (by increasing the activity of iNOS anddecreasing the activity of arginase) and increasing the catabolismof polyamines (by increasing the activity of polyamine oxidase).The neurohormone melatonin exerted significant immunomodulatory effects in liver tissue, reducing the activity of myeloperoxidase (which is associated with the inhibition ofneutrophil infiltration), lowering the level of proinflammatorycytokines and nitric oxide, which significantly prevented the inducedseptic condition. In the liver, melatonin reduced the intensity of oxidativedamage, showed a significant antiapoptotic effect and redirected Largininemetabolism towards polyamine biosynthesis.The results ofthis research showed that melatonin has a great hepatoprotectivepotential during endotoxemia, and can be used as a therapeutic agentin patients with sepsis.

Opis (srp)

Biografija autora: list 150.Bibliografija: listovi 125-149. Datum odbrane: 03.04.2024. Immunology

Jezik

srpski

Datum

2023

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 3.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 3.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode