crocin and Cardiotoxicity

Despite newer advances in cancer treatment, chemotherapy is still one of the most widely used treatment strategies in this field. However, this treatment strategy faces major challenges. Doxorubicin (Dox) is an effective chemotherapeutic agent used to treat various cancers. However, several studies have shown that the use of Dox in therapeutic concentrations is associated with serious side effects, such as cardiac toxicity. The use of natural products in combination with chemotherapeutic agents to reduce side effects is a novel approach, and several studies have shown promising results. In this regard, we examined the effect of Crocin on doxorubicin-induced cardiotoxicity in rat and H9c2 cell line. The in vitro model on H9C2 cells and the in vivo models on rats were treated with doxorubicin. Cell viability, DNA damage, and apoptosis were measured in H9C2 cell line in the presence and absence of Crocin. Oxidative stress and various inflammatory parameters, as well as cardiac function tests, also were assessed in doxorubicin-induced cardiotoxicity animal model in the presence and absence of Crocin. Our results showed that Crocin can significantly decrease apoptosis in H9C2 cell line through a reduction in ROS production and DNA damages. Moreover, evaluation of the effect of Crocin on doxorubicin-induced cardiotoxicity animal model showed that Crocin also can significantly reduce oxidative stress and inflammatory parameters in the serum of the animals. Assessment of cardiac function revealed that Crocin has a significant protective effect against doxorubicin-induced cardiotoxicity in the animal model. Our data indicate that Crocin significantly attenuated doxorubicin-induced cardiotoxicity. Hence, Crocin could be potentially used as an adjuvant treatment in combination with Dox to reduce cardiotoxicity.

Topics: Animals; Apoptosis; Cardiotoxicity; Carotenoids; Doxorubicin; Myocytes, Cardiac; Oxidative Stress; Rats

The effects of Crocin as a cardioprotective material against Aluminum phosphide poisoning by reducing the oxidative stress is investigated.. The level of biomarkers of oxidative stress (Catalase, Superoxide dismutase, Malondialdehyde and Protein carbonyl) were measured in the cell culture model on Human Cardiac Myocyte cells to detect the protective effect of crocin. Initially, to define the pure impact of aluminum phosphide poison and crocin on the heart cells, their effects on the biomarkers quantity in cell line were measured, separately, using the standard related kits. Later the effect of crocin with different concentration as a treatment on the oxidative stress biomarkers of the poisoned heart cells were monitored. Note that in pre-treatment case, the crocin was initially added to the cells before poisoning them. Data were analyzed using the analysis of variance method.. Results showed that crocin treatment reduced the aluminum phosphide (AlP) poisoning effect significantly. The treatment resulted in substantial deviation in the biomarkers of oxidative stress at the pre- and post-treatment phases for all groups. The oxidative markers values of the poisoned cells were recovered by crocin treatment.. Crocin is proposed as a potentially powerful antioxidant to treat the cardiotoxicity caused by aluminum phosphide poisoning.

Topics: Aluminum Compounds; Antidotes; Antioxidants; Biomarkers; Cardiotoxicity; Carotenoids; Catalase; Crocus; Heart; Humans; Malondialdehyde; Myocardium; Myocytes, Cardiac; Oxidative Stress; Pesticides; Phosphines; Phytotherapy; Plant Extracts; Protein Carbonylation; Superoxide Dismutase

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.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cardiotoxicity; Carotenoids; Doxorubicin; Humans; Myocardium; Oxidative Stress; Rats

Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Cardiotonic Agents; Cardiotoxicity; Carotenoids; Cell Line; Cell Survival; Doxorubicin; Electrocardiography; Male; Myocardium; Myocytes, Cardiac; NF-kappa B; Oxidative Stress; Rats, Sprague-Dawley; Signal Transduction; Toll-Like Receptor 2

Arsenic trioxide (ATO) is an excellent therapy for acute promyelocytic leukemia; however, its use is limited due to its cardiotoxicity. Crocin (CRO) possesses abundant pharmacological and biological properties, including antioxidant, anti-inflammatory, and anti-apoptotic. This study examined the cardioprotective effects of crocin and explored their mechanistic involvement in ATO-induced cardiotoxicity. Forty-eight male rats were treated with ATO to induce cardiotoxicity. In combination with ATO, CRO were given to evaluate its cardioprotection. The results demonstrated that CRO administration not only diminished QTc prolongation, myocardial enzymes and Troponin T levels but also improved histopathological results. CRO administration reduced reactive oxygen species generation. However, the CRO administration caused an increase in glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and total sulphydryl levels and a decrease in malondialdehyde content, gamma glutamyl transferase and lipid hydroperoxides levels and proinflammatory cytokines. Importantly, immunohistochemical analysis, real time PCR and western blotting showed a reduction in Caspase-3 and Bcl-2-associated X protein expressions and enhancement of B cell lymphoma-2 expression. Real time PCR and western blotting showed a reduction in proinflammatory cytokines. Moreover, CRO caused an activation in nuclear factor erythroid-2 related factor 2, leading to enhanced Kelch-like ECH-associated protein 1, heme oxygenase-1 and nicotinamide adenine dinucleotide quinone dehydrogenase 1 expressions involved in Nrf2 signaling during ATO-induced cardiotoxicity. CRO was shown to ameliorate ATO-induced cardiotoxicity. The mechanisms for CRO amelioration of cardiotoxicity due to inflammation, oxidative damage, and apoptosis may occur via an up-regulated Keap1-Nrf2/HO-1 signaling pathway.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Arsenic Trioxide; Cardiotoxicity; Carotenoids; Electrocardiography; Heme Oxygenase (Decyclizing); Kelch-Like ECH-Associated Protein 1; Male; Myocardium; NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction

Zearalenone (ZEN) is a mycotoxin from Fusarium species commonly found in food commodities and is known to cause reproductive disorders. Several in vivo studies have shown that ZEN is haematotoxic and hepatotoxic and causes several alterations of immunological parameters. Meantime, the available information on the cardiotoxic effects of ZEN is very much limited. In the present study, we investigated the toxic effects of ZEN in heart tissues of Balb/c mice. We demonstrated that ZEN (40 mg kg(-1) body weight (b.w.)) increased creatine phosphokinase, lactate dehydrogenase, aspartate transaminase, alanine transaminase, total cholesterol and triglyceride levels and induced oxidative stress as monitored by measuring the malondialdehyde level, the generation of protein carbonyls, the catalase and superoxide dismutase activity and the expression of the heat shock proteins (Hsp 70). We also demonstrated that acute administration of ZEN triggers apoptosis in cardiac tissue. Furthermore, we aimed to evaluate the safety and efficacy of crocin (CRO), a natural carotenoid, to prevent ZEN-induced cardiotoxicity in mice. In fact, combined treatment of ZEN with different doses of CRO (50, 100, and 250 mg kg(-1) b.w.) showed a significant reduction of ZEN-induced toxicity for all tested markers in a dose-dependent manner. It could be concluded that CRO was effective in the protection against ZEN-induced toxicity in cardiac tissue.

Topics: Animals; Antioxidants; Apoptosis; Blotting, Western; Cardiotoxicity; Carotenoids; Dose-Response Relationship, Drug; Food Contamination; Heart; Lipid Peroxidation; Mice, Inbred BALB C; Myocardium; Oxidative Stress; Zearalenone

Organophosphate compounds, such as diazinon (DZN), are widely used in agriculture and can lead to formation of reactive oxygen species (ROS) in cardiovascular system. ROS are highly toxic since they can cause serious changes in proteins including ubiquitylation. Crocin (a carotenoid isolated from saffron), has protective effects against DZN cardiotoxicity. In this study level of total protein ubiquitylation as markers of oxidative stress and level of ubiquitin-HIF-1α and P53, known substrates of ubiquitylation, in rat hearts exposed to DZN and crocin were evaluated.. Rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25, 50 mg/kg/day, i. p.) plus DZN, vitamin E (200 IU/kg, i. p., 3 days a week) plus DZN and crocin (50 mg/kg/day, i. p.). Treatments were continued for 4 weeks. Total protein ubiquitylation, total HIF-1α and P53 were analyzed by western blotting. Total HIF-1α and P53 were purified by immunoprecipitation (IP) and ubiquitin- HIF-1α and P53 were analyzed by western blotting.. Higher protein ubiquitylation levels were observed in DZN treated rats. Decrease in ubiquitin-HIF-1α was also shown, and leads to higher HIF-1α protein levels in DZN group. Crocin (50 mg/kg) and vit. E protected cells against DZN protein ubiquitylation. Significant differences were not observed between the ubiquitin - P53 and total P53 protein levels.. Our results showed that ubiquitylation could be considered as a marker of oxidative stress in rats exposed to DZN. Increase in level of HIF-α may compensate adverse effect of DNZ in rat heart.

Topics: Animals; Cardiotonic Agents; Cardiotoxicity; Carotenoids; Crocus; Diazinon; Dose-Response Relationship, Drug; Hypoxia-Inducible Factor 1, alpha Subunit; Insecticides; Male; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Tumor Suppressor Protein p53; Ubiquitination; Vitamin E