2.4 Anti-apoptotic effects
Previous studies have demonstrated the presence of apoptosis during BPD and found that caspase-3, caspase-9 and caspase-12 are important regulators of apoptosis. Li et al.evaluated 50 Wistar rats that received a dose of 25 mg/kg/day caffeine for the first 4 weeks of anexperiment and found that caffeine inhibited caspase 3 activation and reduced apoptosis incardiomyocytes69. Caffeine has also been shown to inhibit apoptosis in a mouse model of BPD, most notably in alveolar epithelial cells. In a hyperoxia-induced mouse model of lung. In terms of transcription of cell death-related mediators, caffeine inhibited the effect of hyperoxia on cell death-related mediators (caspase3, apoptosis-inducing factor(AIF) and glutamate cysteine ligase catalytic subunit (GCLC))51. Teng et al.also demonstrated that caffeine can inhibit endoplasmic reticulum stress-associated apoptosis by reducing the BCl2/Bax ratio and by inhibiting the expression of caspase1262.Moreover, another in vitro study found that caffeine induced apoptosis in lung cancer epithelial cells in a concentration-dependent manner during a G2 phase block of the cell cycle; this was enhanced at a concentration of 5 mM and also induced a TP53 non-dependent G1 phase block70. In addition, high concentrations of caffeine abolished G2 phase block and increased the rates of cell death, whereas low and clinically relevant concentrations of caffeine had no effect on G2 phase block and exerted antioxidant effects59. Dayanim et al found that caffeine reduces the number of ATII cells and increases the levels of apoptosis by decreasing the expression of the A2AR in animal models of hyperoxia71. Therefore, the anti-apoptotic effects of caffeine still need to be investigated further.