Choline is a precursor of the major
neurotransmitter acetylcholine and has been demonstrated beneficial in diverse models of
cardiovascular disease. Here, we sought to verify that
choline protects the heart from DOX-induced
cardiotoxicity and the underlying mechanisms. The results showed that DOX treatment decreased left ventricular ejection fraction and fractional shortening and increased serum cardiac markers and myocardial
fibrosis, which were alleviated by cotreatment with
choline. DOX-induced
cardiotoxicity was accompanied by increases in oxidative stress,
inflammation, and apoptosis, which were rectified by
choline cotreatment. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase-1 (HO-1), which are
antioxidant markers, were lowered by DOX and upregulated by
choline. Moreover, DOX significantly decreased serum
acetylcholine levels and the high-frequency component of heart rate variability and increased serum
norepinephrine levels and the low-frequency component; these effects were rescued by
choline administration. Interestingly, the protective effects of
choline could be partially reversed by administration of the
muscarinic receptor antagonist
atropine. This suggests that
choline might be a promising adjunct therapeutic agent to alleviate DOX-induced
cardiotoxicity.