Protective effect of crocin against arsenic trioxide-induced cardiomyocyte apoptosis: possible involvement the PERK/eIF2α/CHOP-mediated endoplasmic reticulum stress response.

Crocin (CRO) is the main active ingredient of saffron (Crocus sativus) and is known for its significant health benefits. As a promising anticancer agent, arsenic trioxide (As2O3, ATO) is clinically restricted due to its severe cardiotoxicity. Thisstudy aimed toinvestigate the pharmacological mechanisms of CRO in counteracting myocardial injury induced by arsenic trioxide (As2O3, ATO), which is an anti-acute promyelocytic leukemia (APL) drug with great potential but also with obvious cardiac toxicity, both in vivo and in vitro. Rats were pretreated with intraperitoneal injections of 40 or 80 mg/kg/day CRO, followed by an injection of 5 mg/kg/day ATO 6 h later for 14 days. Similarly, H9c2 cardiomyocytes were pre-exposed to 40 or 80 μM CRO for 2 h and then subjected to a 24-h co-incubation with 10 μM ATO. The protective effect of CRO on ATO-induced myocardial damage was evaluated by pathological morphology, biochemical experiments, qRT-PCR, Western blot et al. Cardiac dysfunction was improved in CRO-treated groups, and the level of oxidative stress, imbalances in intracellular calcium homeostasis, as well as cardiomyocyte apoptosis were obviously reduced. Further studies showed that CRO inhibited the abnormally high expression of p-PERK, p-eIF2α and CHOP, which are endoplasmic reticulum stress (ERS)-related proteins, that were induced by ATO. In summary, CRO improves ATO-induced cardiac damage by alleviating oxidative stress, rectifying intracellular calcium imbalance, and inhibiting apoptosis. Moreover, the protective effect of CRO may be closely related to its capacity to diminish ERS through the regulation of the PERK/eIF2α/CHOP pathway.