ubiquinone and Cardiotoxicity

Cardiovascular diseases are the most common cause of death in Poland and in the world. People with cardiovascular disease or high cardiovascular risk require early detection and pharmacotherapy. New methods of prevention and treatment are needed. Coenzyme Q10 (CoQ10) is an essential component of the human body. CoQ10 plays an important role in the biosynthesis of adenosine-5'-triphosphate (ATP) and has antioxidant activity. More and more evidence indicates that CoQ10 is closely related to cardiovascular disorders. Its supplementation may be beneficial in various chronic and acute disorders. Coenzyme Q10 used in heart failure reduces mortality and improves exercise capacity. CoQ10 can reduce the values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in hypertensive patients. CoQ10 supplementation prevents electrocardiographic (ECG) changes in patients taking doxorubicin and has a positive effect on heart function during anthracycline chemotherapy. The review article was based on available literature found in the Medline database and includes preclinical and clinical research. Further research related to CoQ10 can contribute to significant progress in the prevention and treatment of cardiovascular diseases but may also be the basis for increasing the range of indications for this drug.

Topics: Cardiotoxicity; Cardiovascular Diseases; Heart Failure; Humans; Poland; Ubiquinone

Triptolide (TP) is one of the major components of Tripterygium wilfordii, which is a traditional Chinese medicine widely used in the treatment of various autoimmune and inflammatory diseases. However, the cardiotoxicity induced by TP greatly limits its widespread clinical application. In view of the role of ROS-mediated oxidative stress in TP-induced cardiotoxicity, mitoQ, a mitochondria-targeted ROS scavenger, was used in this study to investigate its protective effect against TP-induced cardiomyocyte toxicity and its possible underlying mechanism. Here we demonstrated that mitoQ could significantly attenuate TP-induced cardiotoxicity in cardiomyocyte H9c2 cells, with a remarkable improvement in cell viability and reduction in ROS levels. P62-Nrf2 signaling pathway has been reported to play a critical role in regulating oxidative stress and protecting cells from harmful stimuli. In this study, we found that mitoQ significantly activated p62-Nrf2 signaling pathway in H9c2 cells with or without TP treatment. Moreover, knockdown of p62 or Nrf2 could block the protective effect of mitoQ against TP in H9c2 cells. Taken together, our study demonstrates that mitoQ can alleviate TP-induced cardiotoxicity via the activation of p62-Nrf2 signaling pathway, which provides new potential strategies to combat TP-induced cardiomyocyte toxicity.

Topics: Apoptosis; Cardiotoxicity; Humans; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species; Ubiquinone

Doxorubicin (DOX) is used as an anticancer drug despite its several side effects, especially its irreversible impacts on cardiotoxicity. Coenzyme Q10 (Q10) as a powerful antioxidant and lisinopril (LIS) as an angiotensin-converting enzyme inhibitor seem to provide protection against DOX-induced cardiotoxicity. Therefore, this study aimed to assess the cardioprotective effects of Q10 and LIS against DOX-induced cardiotoxicity in rats. Adult male Sprague-Dawley rats were randomly assigned into the control, LIS, Q10, DOX, DOX + LIS, and DOX + Q10 groups. On day 21, ECG was recorded and the right ventricle was dissected for evaluation of catalase activity and malondialdehyde (MDA) concentration. Additionally, the left ventricle and the sinoatrial (SA) node were dissected to assess the stereological parameters. The results of ECG indicated bradycardia and increase in QRS duration and QT interval in the DOX group compared to the control group. Meanwhile, the total volumes of the left ventricle, myocytes, and microvessels and the number of cardiomyocyte nuclei decreased, whereas the total volume of the connective tissue and the mean volume of cardiomyocytes increased in the DOX group. On the other hand, the SA node and the connective tissue were enlarged, while the volume of the SA node nuclei was reduced in the DOX group. Besides, catalase activity was lower and MDA concentration was higher in the DOX-treated group. Q10 could recover most stereological parameters, catalase activity, and MDA concentration. LIS also prevented some stereological parameters and ECG changes and improved catalase activity and MDA concentration in the DOX group. The findings suggested that Q10 and LIS exerted cardioprotective effects against DOX-induced cardiac toxicity.

Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Catalase; Disease Models, Animal; Doxorubicin; Electrocardiography; Heart Conduction System; Heart Diseases; Heart Rate; Lisinopril; Male; Malondialdehyde; Myocytes, Cardiac; Rats, Sprague-Dawley; Ubiquinone

In the present study, we investigated the cardioprotective effects of coenzyme Q10 (Q10) against doxorubicin (DOXO) induced cardiomyopathy. Twenty adult rats were distributed in four experimental groups: group 1 received NaCl 0.9% at 1 ml/day for 14 days; group 2 received Q10 at 1 mg/kg/day for 14 days; group 3 received initial 7 days of treatment with NaCl 0.9% followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of NaCl; and group 4 received initial 7 days of Q10 1 mg/kg/day, followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of Q10. At the end of 14 days, systolic, diastolic and mean blood pressure, electrocardiogram (ECG), complete blood count, and serum biochemical profile were evaluated. We also analyzed heart histological and ultrastructure analysis, and estimated heart's oxidative stress and lipid peroxidation. DOXO administration altered ECG, with increase heart rate, P-wave duration, PR interval duration, and T-wave amplitude. All the parameters were significantly reduced following Q10 treatment. DOXO also caused increase in CK, CK-MB, LDH, and urea levels, which were not mitigated by Q10 treatment. However, Q10 reduced oxidative stress by interfering with superoxide dismutase, significantly decreasing lipid peroxidation in heart tissue. DOXO administration also leads to several histological and ultrastructure alterations including cardiomyocyte degeneration and intense intracelullar autophagosomes, all minimized by Q10 treatment. Q10 treatment prevented the ECG changes, minimized oxidative stress, lipid peroxidation, and DOXO-induced heart tissue alterations. Our findings suggest that pre- and post-treatment with Q10 exerts potential cardioprotective effect against the DOX-induced cardiotoxicity.

Topics: Animals; Antioxidants; Cardiomyopathies; Cardiotoxicity; Disease Models, Animal; Doxorubicin; Lipid Peroxidation; Myocytes, Cardiac; Oxidative Stress; Rats, Wistar; Ubiquinone

Topics: Cardiotoxicity; Cisplatin; Humans; Mitochondria; Oxidative Stress; Trimetazidine; Ubiquinone

The objective of this study was to investigate the effects of trimetazidine (TMZ) and coenzyme Q10 (CoQ10) on cisplatin-induced cardiotoxicity in rat cardiomyocytes.. Rat cardiomyocytes were isolated and subjected to cisplatin (200 μM) treatment with and without TMZ (200 μM) and CoQ10 (200 mg/L) pretreatment. The cell viability, apoptosis, oxidant and antioxidant indicators, and mitochondrial dysfunction were examined.. TMZ or CoQ10 significantly attenuated cisplatin-induced cell viability inhibition (p<0.01) and apoptosis (p<0.001), and the combined use of TMZ and CoQ10 pretreatment exerted a pronounced effect compared to the effects of using each of these agents individually (p<0.05). TMZ or CoQ10 inhibited the levels of reactive oxidative species (ROS, p<0.01) and malondialdehyde (MDA, p<0.001 and p<0.01, respectively), elevated the activities of antioxidant enzymes superoxide dismutase (SOD, p<0.01) and catalase (CAT, p<0.01 and p<0.05, respectively), evidently enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2, p<0.05), alleviated mitochondrial membrane potential (ΔΨm) loss (p<0.05), and down-regulated the release of cytochrome c (cyto-c) into the cytosol (p<0.01) in cisplatin-treated cells. The combined use of TMZ and CoQ10 treatment was more effective than using either agent alone (p<0.01 for ROS, MDA, CAT, and cytosolic cyto-c; p<0.05 for SOD, nuclear Nrf2, and ΔΨm loss).. TMZ and CoQ10 showed protective effects against cisplatin-induced cardiotoxicity via attenuating oxidative stress.

Topics: Animals; Antioxidants; Apoptosis; Cardiotoxicity; Cell Survival; Cisplatin; Drug Therapy, Combination; Mitochondria; Myocytes, Cardiac; Rats; Trimetazidine; Ubiquinone

Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L-carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L-carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.

Topics: Animals; Cardiotoxicity; Carnitine; Doxorubicin; Female; Heart Diseases; Myocardium; Oxidative Stress; Rats; Rats, Wistar; Ubiquinone

The aim of this study was to assess the possible modulatory effects of rosuvastatin and/or ubiquinone on trastuzumab (TRZ)-induced cardiotoxicity in mice. One hundred and twenty mice were divided into six equal groups as follows: control group; TRZ group; TRZ+carboxymethyl cellulose group; TRZ+rosuvastatin group; TRZ+Ubiquinone group and TRZ+rosuvastatin+Ubiquinone group. Serum creatine kinase (CK-MB), lactate dehydrogenase (LDH), troponin I and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) were measured. Also, tissue malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx), interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β1) and signal transducers and activators of transcription-3 (STAT-3) were determined. Also, echocardiography was performed. Parts of the heart were subjected to histopathological, immunohistochemical and electron microscopic examination. Administration of rosuvastatin and/or ubiquinone to TRZ-treated mice induced significant increase in tissue GPx, CAT and STAT-3 with significant decrease in serum CK-MB, LDH, troponin I, NT-pro BNP, tissue MDA, TGF-β1 and IL-6 and improved the histopathological, immunohistochemical, echocardiographic and electron microscopic changes compared to the group that received TRZ alone. These changes were significant in rosuvastatin/ubiquinone combination group compared to the use of each of these drugs alone. In conclusion, rosuvastatin/ubiquinone combination may represent a new therapeutic modality to ameliorate TRZ-induced cardiotoxicity.

Topics: Animals; Cardiotoxicity; Cytokines; Inflammation; Male; Mice; Mice, Inbred BALB C; Oxidative Stress; Rosuvastatin Calcium; Signal Transduction; STAT3 Transcription Factor; Transforming Growth Factor beta1; Trastuzumab; Ubiquinone

Present study focuses on enhancing oral antitumor efficacy and safety of Dox-LCNPs in combination with CoQ10-LCNPs. Drug-loaded-LCNPs were prepared by solvent-diffusion-evaporation method and optimized. Median effect analysis suggested dose-reduction-index of 16.84- and 5.047-fold and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor efficacy was found to be significantly higher (~1.76- and ~4.5-fold) for the combination as compared to Dox-LCNPs (per oral) and Adriamycin (i.v.) respectively. Notably, level of residual tumor burden was insignificant (P>0.05) after 30days in case of combination and LipoDox® (i.v.). Interestingly, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration.. This study describes the use of liquid crystalline nanoparticles containing coenzyme Q10 and doxorubicin. The nano-conjugates not only provided an enhanced oral treatment option for a tumor model, but prevented cardiotoxicity, a major complication of this drug when delivered via conventional methods.

Topics: Administration, Intravenous; Administration, Oral; Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Cardiotoxicity; Cell Line, Tumor; Doxorubicin; Drug Therapy, Combination; Female; Humans; Liquid Crystals; Nanoparticles; Rats, Sprague-Dawley; Ubiquinone; Vitamins