Response of the Glutathione (GSH) Antioxidant Defense System to Oxidative Injury in Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a neonatal intestinal disease associated with oxidative stress. The targets of peroxidation and the role innate epithelial antioxidant defense system are ill-defined. We hypothesized that stress in NEC correlates oxidized GSH redox potentials, lipid peroxidation, dysfunctional system. Methods: Intestinal samples from infants +/− were generated into enteroids incubated lipopolysaccharide (LPS) hypoxia to induce experimental NEC. HPLC assayed potentials. Lipid was measured by flow cytometry. Immunoblotting glutathione peroxidase 4 (Gpx4) expression. Results: potentials more tissue as compared controls. radicals NEC-induced significantly increased. Human active treated enteroid cultures revealed decreased levels Gpx4. Conclusions: ability intestine mitigate radical accumulation plays its capacity overcome Accumulation confirmed after treatment NEC-triggering stimuli. Decreased Gpx4 diminishes cell’s effectively neutralize radicals. When overwhelms machinery, cellular death ensues. Identification mechanisms behind GSH-dependent enzyme dysfunction may provide insights strategies for reversing damage.