Hyperbilirubinemia Protects against Aging-Associated Inflammation and Metabolic Deterioration

0465951 - FGÚ 2017 RIV US eng J - Článek v odborném periodiku
Zelenka, J. - Dvořák, Aleš - Alán, Lukáš - Zadinová, M. - Haluzík, M. - Vítek, L.
Hyperbilirubinemia Protects against Aging-Associated Inflammation and Metabolic Deterioration.
Oxidative Medicine and Cellular Longevity. Roč. 2016, č. 2016 (2016), č. článku 6190609. ISSN 1942-0900. E-ISSN 1942-0994
Grant CEP: GA ČR(CZ) GPP305/12/P388
Institucionální podpora: RVO:67985823
Klíčová slova: hyperbilirubinemia * ROS * senescence
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 4.593, rok: 2016

Mild constitutive hyperbilirubinemia is associated with a reduced risk of cardiovascular diseases, diabetes, and cancer. Since these pathologies are associated with aging, inflammation, and oxidative stress, we investigated whether hyperbilirubinemia interferes with ROS homeostasis in cell cultures and with inflammation, senescence, and mitochondrial dysfunction in aged rats. Human embryonic kidney cells and rat primary fibroblasts showed a dose-dependent decrease in the ratio of oxidized/reduced glutathione, intracellular H2O2 levels, and mitochondrial ROS production, with increasing bilirubin concentrations in the culture media. Compared to their normobilirubinemic siblings, aged hyperbilirubinemic Gunn rats showed significantly smaller amounts of visceral fat, better glucose tolerance, and decreased serum levels of proinflammatory cytokines TNF alpha, IL-1 beta, and IL-18. Simultaneously, livers from Gunn rats showed decreased expression of senescence markers and cell cycle inhibitors p21 and p16. Mitochondria from aged Gunn rats showed higher respiration and lower H2O2 production compared to controls. In conclusion, we demonstrated that mildly elevated serum bilirubin is generally associated with attenuation of oxidative stress and with better anthropometric parameters, decreased inflammatory status, increased glucose tolerance, fewer signs of cellular senescence, and enhanced mitochondrial function in aged rats.
Trvalý link: http://hdl.handle.net/11104/0264412