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Antioxidant and antiinflammatory effects of bilirubin.
Valášková, Petra ; Muchová, Lucie (advisor) ; Martínková, Markéta (referee) ; Dvořák, Karel (referee)
For a long time, bilirubin (BR) has been considered a waste molecule with potential toxic effects especially on the central nervous system. Later, it was found that BR exhibited cytoprotective effects and mildly elevated BR levels showed antioxidant, anti-inflammatory and immunomodulatory properties, however, exact mechanisms of the anti-inflammatory actions of BR have not been fully understood yet. The main aim of this study was to assess the protective effects of BR using experimental in vivo and in vitro models in relation to inflammation and oxidative stress. Partial goal was to establish validated analytical method for determination of BR and lumirubin. Gunn and heterozygous rats were treated with lipopolysaccharide (LPS, 6 mg/kg, IP) or vehicle (saline). After 12 hours, blood and organs were collected for analyses of inflammatory and hepatic injury markers. Primary rat hepatocytes were treated with BR and TNF-α, HepG2 and SH-SY5Y cell lines were treated with BR and chenodeoxycholic acid. LPS-treated Gunn rats had a significantly decreased inflammatory response and hepatic injury compared to LPS- treated normobilirubinemic controls. We found different profile of leukocytes subsets and decreased systemic mRNA expressions and concentrations of IL-6, TNF-α, IL-1β and IL-10 in Gunn rats. Hepatic mRNA...
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