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.