Abstract
Doxorubicin (DOX) is a well-known chemotherapeutic drug for most malignancies including breast cancer and leukemia whilst the usage of DOX is limited owing to its cardiotoxicity. In the present study, we aimed to investigate the effects of crocin on doxorubicin-induced cardiotoxicity in rats. Forty rats were randomly divided into four groups: (a) control [received normal saline as a dose of 1 ml/kg by intraperitoneal injection (ip) for 15 days], (b) crocin (received crocin as a dose of 40 mg/kg/24h by ip for 15 days), (c) DOX (received DOX as a dose of 2 mg/kg/48h by ip in six injection, cumulative dose 12 mg/kg), and (d) DOX+crocin (received DOX as a dose of 2 mg/kg/48h by ip in six injection, and crocin as a dose of 40 mg/kg/24h i.p for 15 days). As compared to the controls, the results showed that DOX administration caused significant increases in lipid indices [triglyseride (TG), low-dencity lipoproteins (LDL) (p<0.001), and very low-dencity lipoproteins (VLDL) (p<0.005)], oxidative stress parameters [malondialdehyde (MDA) and total oxidant status (TOS) (p<0.001)] and cardiac markers [creatine kinase-muscle/brain (CK-MB) and cardiac troponin I (cTnI) (p<0.001)]. Besides, significant decreases in antioxidant defense systems [glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) (p<0.001)] were observed. The present study also demonstrated that co-administration of crocin with DOX significantly ameliorated the lipid profile (p<0.005), cardiac markers (p<0.005), and oxidative stress indices (p<0.001) as compared to DOX group. Histopathologically, significant increase in the mean histopathological damage score (MHDS) was found in the DOX group as compared to the controls (p<0.001). In contrast, the administration of crocin with DOX alleviated MHDS in myocardium (p<0.001). Taken together, our results reveal that crocin might be a cardioprotective agent in DOX-treated patients for cancer.
Highlights
Doxorubicin (DOX), one of the anthracycline glicoside antibiotic, is a frequently used as a chemotherapeutic drug owing to treat several malignancies in patients, such as breast cancer, leukemia, and sarcoma by causing DNA intercalation and inhibiting the DNA replication (Migrino et al 2008, Swain et al 2003)
The levels of cardiac oxidative stress markers and tissue antioxidant contents showed no pathological changes between control and crocin groups
Statistical analysis showed that DOX treatment resulted in dramatically increases (p < 0.001) in the cardiac levels of MDA and Total oxidant status (TOS) relative to values measured within the control group
Summary
Doxorubicin (DOX), one of the anthracycline glicoside antibiotic, is a frequently used as a chemotherapeutic drug owing to treat several malignancies in patients, such as breast cancer, leukemia, and sarcoma by causing DNA intercalation and inhibiting the DNA replication (Migrino et al 2008, Swain et al 2003). The main mechanism of cardiotoxicity caused by DOX-induced toxicity is unknown, DOX raises inflammation and oxidative stress in heart tissue including lipid peroxidation, mitochondrial DNA damage, apoptosis as well as deteriorate calcium homeostasis (Li et al 2016, Octavia et al 2012) Increased both calcium and reactive oxygen species (ROS) in mitochondria leads to generate lipid peroxidation and the formation of oxidative injury and cell membran of cardiyomyocytes (Zhou et al 2001a). An increase oxidative stress which raised after DOX treatment contributes to the activation of apoptotic signaling pathways and leads to apoptotic cell death of myocytes (Octavia et al 2012) It seems that myocardial infarction, heart failure and cardiac dysfunction are associated with myocardial apoptosis (Abbate et al 2006, Takemura et al 2013). Due to the high effectiveness of DOX as a chemotherapeutic drug in many cancers, recent studies are associated with preventing and treating its adverse cardiac effects of DOX by using phytochemicals or drug along with DOX (Abushouk et al 2017, Durdagi et al, Oner et al 2019)
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