Cristina Bellarosa

Cristina Bellarosa

Italian Liver Foundation

Title: Effect of Mild Hyperbilirubinemia on two in vitro models of Metabolic Syndrome


Cristina Bellarosa, PhD is a senior scientist at Italian Liver Foundation, Trieste, Italy. She works in the field of Bilirubin since 2003 under the supervision of Prof. Claudio Tiribelli, MD. Bilirubin is one of the main research area of Italian Liver Foundation. Every two years the Foundation organize an international meeting that put together all the experts working in the field worldwide. Her scientific research activity was mainly focused on studying the molecular mechanisms of bilirubin neurotoxicity in in vitro models, with a particular focus on bilirubin cell signaling. Recently she moved to study the bilirubin protective role. She works as scientific lab tutor of PhD students, ungraduate students and fellows.


Background: Mildly elevated serum unconjugated bilirubin has beneficial effects on oxidative stress-mediated diseases. UGT1A1 variants in Gilbert Syndrome resulting in hyperbilirubinemia may confer a strong genetic advantage. Life-long genetically elevated bilirubin level are protective against the development of type 2 Diabetes (T2D) and the progression of nephropathy in T2D. The prevalence of hypertension was up to 25% lower in patients with bilirubin >1mg/dL, as serum levels of cholesterol and triacylglycerol. Serum bilirubin is negatively related to cardiovascular disease (CVD) and to incidence of metabolic syndrome. The protection provided by increased level of bilirubin appears to be largely due to its antioxidant and anti-inflammatory properties. Strategies to boost the bioavailability of bilirubin or to mimic Gilbert syndrome may prove to be an attractive intervention in cardiovascular disease and metabolic syndrome.
Aim: To study the protective role of mild hyperbilirubinemia on oxidative stress, inflammation and ER-stress in two in vitro models of metabolic syndrome.
Methods: Heart endothelial murine H5V cells were treated with palmitic acid (PA) and kidney tubular epithelial HK-2 cells were treated with Advanced Glycated End Products (AGE-BSA). Target genes mRNA expression, cell viability and intracellular ROS was assessed in the presence of bilirubin pretreatment or posttreatment.
Results: 24h of PA treatment on H5V cells causes cell necrosis and mRNA induction of HO-1, IL-6, GRP78 and CHOP; treatment of 72 h induces E-Selectin, V-CAM, ICAM and iNOS. UCB pre-treatment reverts cell necrosis, reduces CHOP, IL-6 and iNOS expression and increases HO-1. Treatment of HK-2 cells with AGE-BSA for 72h resulted in significative variation of IL-8, HIF1a, HO-1, GPX and Catalase mRNA expression and increases intracellular ROS. UCB pre-treatment reverses the HO1 and GPX mRNA reduction, reduces IL-8 and HIF1a mRNA induction and ROS intracellular levels. Conclusion: Bilirubin pretreatment modulates cell viability, ROS production and mRNA gene expression in the systems studied.