ubiquinone and Hemorrhage

Topics: Anemia; Animals; Chickens; Chromium Isotopes; Erythrocyte Aging; Erythrocytes; Erythropoiesis; Haplorhini; Hematopoietic System; Hemolysis; Hemorrhage; Humans; Hydrogen Peroxide; Macaca; Mice; Oxidation-Reduction; Rats; Species Specificity; Turkeys; Ubiquinone; Vitamin E; Vitamin E Deficiency

To determine the risk of bleeding and supratherapeutic international normalized ratios (INRs) associated with use of complementary and alternative medicine (CAM) in patients receiving warfarin.. Prospective, longitudinal study.. An acute care, academic and research hospital in Canada.. A total of 171 adults who were prescribed warfarin anticoagulation therapy for an expected duration of at least 4 months after enrollment.. Patients were asked to complete a 16-week diary by recording bleeding events and exposure to factors previously reported to increase the risk of bleeding and supratherapeutic INRs, including CAM consumption.. Prescription, medical, and laboratory records were reviewed. Risk factors for bleeding events and supratherapeutic INR (at least 0.5 units above the target range) were evaluated longitudinally by using generalized estimating equation (GEE) modeling. Of the 171 patients completing a diary, 87 (51%) reported at least one bleeding event and 36 (21%) had a supratherapeutic INR. Seventy-three patients (43%) indicated they had used at least one CAM product previously reported to interact with warfarin. Warfarin use of less than 3 months' duration was the only statistically significant risk factor identified for supratherapeutic INR. The CAM therapies associated with an increased risk of self-reported bleeding included cayenne, ginger, willow bark, St. John's wort, and coenzyme Q(10). Use of more than one CAM while receiving warfarin was also a significant risk factor. Two CAMs were independently associated with an increased risk of self-reported bleeding: coenzyme Q(10) (odds ratio [OR] 3.69, 95% confidence interval [CI] 1.88-7.24) and ginger (OR 3.20, 95% CI 2.42-4.24). Other risk factors significantly associated with increased bleeding included high target INR (2.5-3.5), diarrhea, acetaminophen use, increased alcohol consumption, and increased age.. The use of CAM by patients receiving warfarin is common, and consumption of coenzyme Q(10) or ginger appears to increase the risk of bleeding in this population.

Topics: Acetaminophen; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Canada; Coenzymes; Complementary Therapies; Diarrhea; Dietary Supplements; Drug Interactions; Ethanol; Female; Hemorrhage; Herb-Drug Interactions; Humans; International Normalized Ratio; Longitudinal Studies; Male; Middle Aged; Phytotherapy; Plants, Medicinal; Prospective Studies; Risk Factors; Ubiquinone; Vitamins; Warfarin; Zingiber officinale

Cerebral brain hemorrhage is associated with the highest mortality and morbidity despite only constituting approximately 10-15% of all strokes classified into intracerebral and intraventricular hemorrhage where most of the patients suffer from impairment in memory, weakness or paralysis in arms or legs, headache, fatigue, gait abnormality and cognitive dysfunctions. Understanding molecular pathology and finding the worsening cause of hemorrhage will lead to explore the therapeutic interventions that could prevent and cure the disease. Mitochondrial ETC-complexes dysfunction has been found to increase neuroinflammatory cytokines, oxidative free radicals, excitotoxicity, neurotransmitter and energy imbalance that are the key neuropathological hallmarks of cerebral hemorrhage. Coenzyme Q10 (CoQ10), as a part of the mitochondrial respiratory chain can effectively restore these neuronal dysfunctions by preventing the opening of mitochondrial membrane transition pore, thereby counteracting cell death events as well as exerts an anti-inflammatory effect by influencing the expression of NF-kB1 dependent genes thus preventing the neuroinflammation and energy restoration. Due to behavior and biochemical heterogeneity in post cerebral brain hemorrhagic pattern different preclinical autologous blood injection models are required to precisely investigate the forthcoming therapeutic strategies. Despite emerging pre-clinical research and resultant large clinical trials for promising symptomatic treatments, there are very less pharmacological interventions demonstrated to improve post operative condition of patients where intensive care is required. Therefore, in current review, we explore the disease pattern, clinical and pre-clinical interventions under investigation and neuroprotective methodologies of CoQ10 precursors to ameliorate post brain hemorrhagic conditions.

Topics: Animals; Brain; Cognitive Dysfunction; Hemorrhage; Humans; Memory; Mitochondria; Neuroprotection; Neuroprotective Agents; Ubiquinone

Oxidative stress associated with hemorrhagic shock and reperfusion (HSR) results in the production of superoxide radicals and other reactive oxygen species, leading to cell damage and multiple-organ dysfunction. We sought to determine if MitoQ, a mitochondria-targeted antioxidant, reduces morbidity in a rat model of HSR by limiting oxidative stress.. HSR was achieved in male rats by arterial blood withdrawal to a mean arterial pressure of 25 ± 2 mm Hg for 1 hour before resuscitation. MitoQ (5 mg/kg), TPP (triphenylphosphonium, 5 mg/kg) or saline (0.9% vol./vol.) was administered intravenously 30 minutes before resuscitation, followed by an intraperitoneal administration (MitoQ, 20 mg/kg) immediately after resuscitation (n = 5 per group). Morbidity was assessed based on cumulative markers of animal distress (0-10 scale). Rats were sacrificed 2 hours after procedure completion, and liver tissue was collected and processed for histology or assayed for lipid peroxidation (thiobarbituric acid reactive substance [TBARS]) or endogenous antioxidant (catalase, glutathione peroxidase [GPx], and superoxide dismutase) activity.. HSR significantly increased morbidity as well as TBARS and catalase activities versus sham. Conversely, no difference in GPx or superoxide dismutase activity was measured between sham, HSR, and TPP, MitoQ administration reduced morbidity versus HSR (5.8 ± 0.3 vs. 7.6 ± 0.3; p < 0.05), while TPP administration significantly reduced hepatic necrosis versus both HSR and HSR-MitoQ (1.2 ± 0.1 vs. 2.0 ± 0.2 vs. 1.9 ± 0.2; p < 0.05, n = 5). Analysis of oxidative stress demonstrated increased TBARS and GPx in HSR-MitoQ versus sham (12.0 ± 1.1 μM vs. 6.2 ± 0.5 μM and 37.9 ± 3.0 μmol/min/mL vs. 22.9 ± 2.7 μmol/min/mL, TBARS and GPx, respectively, n = 5; p < 0.05). Conversely, catalase activity in HSR-MitoQ was reduced versus HSR (1.96 ± 1.17 mol/min/mL vs. 2.58 ± 1.81 mol/min/mL; n = 5; p < 0.05). Finally, MitoQ treatment decreased tumor necrosis factor α (0.66 ± 0.07 pg/mL vs. 0.92 ± 0.08 pg/mL) and interleukin 6 (7.3 ± 0.8 pg/mL vs. 11 ± 0.9 pg/mL) versus HSR as did TPP alone (0.58 ± 0.05 pg/mL vs. 0.92 ± 0.08 pg/mL; 6.7 ± 0.6 pg/mL vs. 11 ± 0.9 pg/mL; n = 5; p < 0.05).. Our data demonstrate that MitoQ treatment following hemorrhage significantly limits morbidity and decreases hepatic tumor necrosis factor α and interleukin 6. In addition, MitoQ differentially modulates oxidative stress and hepatic antioxidant activity.

Topics: Animals; Antioxidants; Catalase; Enzyme-Linked Immunosorbent Assay; Hemorrhage; Immunohistochemistry; Inflammation; Lipid Peroxidation; Liver; Male; Organophosphorus Compounds; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Resuscitation; Thiobarbituric Acid Reactive Substances; Ubiquinone

Antioxidants occasionally have become prooxidants when a large amount was ingested. The haemorrhagic toxicity of butylated hydroxytoluene, a synthetic antioxidant, may involve such a mechanism. This study investigated whether haemorrhage is induced by overdoses of tocopherols, beta-carotene, ubiquinone or L-ascorbic acid, which are representative biological antioxidants. Male Jcl:SD rats (six rats/group) were fed d-alpha, d-beta, d-gamma or d-delta-tocopherols, ubiquinone Q-10, beta-carotene or retinol acetate at a level of 0.5%, or L-ascorbic acid at 5% in the diet for 7 days. Only two rats given retinol acetate died with lung haemorrhages. Haemorrhages were observed in five or six, six, one, one, one or one of six surviving rats given d-alpha, d-beta or d-gamma-tocopherols, ubiquinone Q-10, beta-carotene or retinol acetate, respectively (except for a retinol group in which four rats survived). Major haemorrhages were noted in the epididymis. In the alpha-, beta- and gamma-tocopherol, ubiquinone Q-10, beta-carotene or retinol acetate-treated groups, prothrombin and kaoline-activated partial thromboplastin time indices were 26-28, 37, 59, 42, 63 and 65% or 27-28, 35, 65, 38, 59 and 28%, respectively, of the control values. Only the prothrombin index was significantly decreased to 67% in delta-tocopherol-administered rates, whereas controls and those receiving L-ascorbic acid showed no signs of bleeding or coagulation defect. The same tendency was also seen in the decreasing effect on vitamin K-dependent blood coagulation factors. These results suggest that the four naturally occurring tocopherols have a tendency to cause haemorrhage in the order of alpha > beta > gamma > delta, and ubiquinone Q-10 and beta-carotene als0o have relatively strong and weak haemorrhagic effects, respectively, with regard to prothrombin and partial thromboplastin time indices.

Topics: Adjuvants, Immunologic; Analysis of Variance; Animals; Anticarcinogenic Agents; Antineoplastic Agents; Ascorbic Acid; beta Carotene; Blood Coagulation; Carotenoids; Diterpenes; Epididymis; Exophthalmos; Eye; Hemorrhage; Male; Prothrombin Time; Rats; Rats, Sprague-Dawley; Retinyl Esters; Stereoisomerism; Thromboplastin; Ubiquinone; Vitamin A; Vitamin E

Topics: Adult; Aged; Blood Pressure; Child, Preschool; Female; Hemorrhage; Humans; Infant; Infant, Newborn; Injections, Intravenous; Male; Middle Aged; Pulse; Ubiquinone