Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia.

Bronchopulmonary dysplasia (BPD) is a common lung disease affecting premature infants that develops after exposure to supplemental oxygen and reactive oxygen intermediates. Extracellular superoxide dismutase (SOD3) is an enzyme that processes superoxide radicals and has been shown to facilitate vascular endothelial growth factor (VEGF) and nitric oxide (NO) signaling in vascular endothelium. We utilized a mouse model of neonatal hyperoxic lung injury and SOD3 knockout (KO) mice to evaluate its function during chronic hyperoxia exposure. Wild-type age-matched neonatal C57Bl/6 (WT) and SOD3-/- (KO) mice were placed in normoxia (21% FiO2, RA) or chronic hyperoxia (75% FiO2, O2) within 24 h of birth for 14 days continuously and then euthanized. Lungs were harvested for histologic evaluation, as well as comparison of antioxidant enzyme expression, SOD activity, VEGF expression, and portions of the NO signaling pathway. Surprisingly, KO-O2 mice survived without additional alveolar simplification, microvascular remodeling, or nuclear oxidation when compared to WT-O2 mice. KO-O2 mice had increased total SOD activity and increased VEGF expression when compared to WT-O2 mice. No genotype differences were noted in intracellular antioxidant enzyme expression or the NO signaling pathway. These results demonstrate that SOD3 KO mice can survive prolonged hyperoxia without exacerbation of alveolar or vascular phenotype.

Glycerol derived process contaminants in refined coconut oil induce cholesterol synthesis in HepG2 cells.

Despite its 50-year history, the conventional diet-heart hypothesis holding that dietary saturated fats raise serum cholesterol, and with it, cardiovascular risk, remains controversial. Harsh chemical and physical treatment generates process contaminants, and refined oils raise serum and tissue cholesterol in vivo independent of saturated fat content. We developed an in vitro bioassay for rapidly assessing the influence of oils on cholesterol metabolism in the human liver HepG2 cell line, and tested it using coconut oil (CO) of various stages of refinement. CO was dissolved with dipalmitoyl phosphatidylcholine (DPPC) surfactant, solvent evaporated, and emulsified into fat-free cell culture media. After 24 h treatment cellular cholesterol and triacylglycerol increased; HMG-CoA Reductase (HMGCR) increased and CYP7A1 (cholesterol 7α-hydroxylase) decreased with sequential processing steps, deacidification, bleaching, deodorization, while fatty acid profiles were not affected. Glycerol-derived process contaminants glycidyl esters and monochloropropandiol (MCPD) increased with processing. Addition of glycidyl or MCPD to virgin CO (VCO) had similar effects to processing, while addition of phenolic antioxidants to fully refined CO reduced HMGCR and increased CYP7A1. We conclude that harsh processing creates contaminants that raise cholesterol levels in vitro, consistent with a role as a contributing atherosclerotic factor.