Crocin protects against cardiotoxicity induced by doxorubicin through TLR-2/NF-κB signal pathway in vivo and vitro

Doxorubicin (DOX) is widely used to treat multiple of tumors, but its clinical trials are allied with some serious adverse events mainly cardiac functional abnormalities. So the objective of our investigation is to identify the cardioprotective action of crocin (CRO), a natural compound derived from saffron, against DOX-induced cardiotoxicity. CRO was injected intraperitoneally (i.p.) to rats for sixconsecutive days and DOX (i.p.) was administered on the fourth day. H9c2 cells were treated with DOX for 24 h after being pre-treated by CRO for 2 h. CROreduced tachycardiaand J-point elevation,decreased the levelsof serum creatine kinase, lactate dehydrogenase,glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase.CRO exerted positive effect on DOX-induced ROS productionand changes of oxidative stress biomarkers. CRO significantlydecreased intracellular Ca²⁺ concentration andincreased mitochondria membrane potentialin H9c2 cells. CRO also resisted the DOX-induced high expressionof tumor necrosis factor-αand interleukin-6, inhibitedapoptosisand improved the abnormal expression levels of Bcl-2, Bax and Caspase-3 proteins.CRO obviously restrained DOX-mediatedhigh expression of toll-like receptor-2 (TLR-2) and nuclear factor kappa-B (NF-κB) in ventricular tissue. Inbrief,CRO distinctly restrained DOX-mediated cardiotoxicity by inhibiting oxidative stress, inflammation, apoptoticandredressingcardiomyocyte calcium dyshomeostasis and mitochondria damage.These cardioprotective effects may berelated closely with the TLR2/NF-κB pathway.

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