Zelenka 2016 Oxid Med Cell Longev
|Zelenka J, Dvořák A, Alán L, Zadinová M, Haluzík M, Vítek L (2016) Hyperbilirubinemia protects against aging-associated inflammation and metabolic deterioration. Oxid Med Cell Longev ID 6190609:10p.|
Abstract: 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 TNFα, IL-1β, and IL-18. Simultaneously, livers from Gunn rats showed decreased expression of senescence markers, 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, as well as enhanced mitochondrial function in aged rats.
• Keywords: Aging, Antioxidants, Bilirubin, Fibroblasts, Gunn rats, Hyperbilirubinemia, Inflammation, Mitochondria, Mitochondrial dysfunction, Senescence, Oxidative stress, T-Rex-293 cells
• O2k-Network Lab: CZ Prague Jezek P
Labels: MiParea: Respiration Pathology: Aging;senescence Stress:Oxidative stress;RONS Organism: Rat Tissue;cell: Liver, Kidney, Fibroblast Preparation: Intact cells, Isolated mitochondria
Coupling state: ROUTINE