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.