2.2 Antioxidant effects
Increased oxidative stress due to exposure to hyperoxia in preterm infants is an important factor in the development of BPD.Caffeine has been shown to exert antioxidant effects in the nervous system58. Oxidative stress can lead to an increase in reactive oxygen species(ROS) and damage to cellular deoxyribonucleic acid (DNA) and lipid oxidation. In an in vitro model of pulmonary oxygen toxicity in human and mouse lung epithelial cells, a low concentration of caffeine (0.01 mM) reduced hydrogen peroxide (H2O2)levels but increased them at high concentrations of 1 mM59. Caffeine reduced hyperoxia-induced oxidative damage in mouse lung DNA and lipids, as well as increased superoxide dismutase, heme oxygenase-1 and Nrf2/Keap1 gene expression; it also blocked the expression levels of key proteins and superoxide dismutase (SOD) in oxidative stress, achieved antioxidant effects at different time points, and attenuated oxidative stress damage60. In addition, endoplasmic reticulum stress is one of the major manifestations of oxidative stress. Caffeine may have the pharmacological propertiesto improve leptin resistance by reducing endoplasmic reticulum stress61.Teng et al.confirmed that caffeine treatment attenuated markers of endoplasmic reticulum stress and downstream effectors (C/EBP homologous protein (CHOP) or the splicing of X-box binding protein 1 (XBP-1) )and attenuated the hyperoxia-induced oxidative stress-induced impairment of alveolar formation 62.