coenzyme-q10 and Hepatitis

It is well established that low birth weight and accelerated postnatal growth increase the risk of liver dysfunction in later life. However, molecular mechanisms underlying such developmental programming are not well characterized, and potential intervention strategies are poorly defined.. We tested the hypotheses that poor maternal nutrition and accelerated postnatal growth would lead to increased hepatic fibrosis (a pathological marker of liver dysfunction) and that postnatal supplementation with the antioxidant coenzyme Q10 (CoQ10) would prevent this programmed phenotype.. A rat model of maternal protein restriction was used to generate low-birth-weight offspring that underwent accelerated postnatal growth (termed "recuperated"). These were compared with control rats. Offspring were weaned onto standard feed pellets with or without dietary CoQ10 (1 mg/kg body weight per day) supplementation. At 12 mo, hepatic fibrosis, indexes of inflammation, oxidative stress, and insulin signaling were measured by histology, Western blot, ELISA, and reverse transcriptase-polymerase chain reaction.. Hepatic collagen deposition (diameter of deposit) was greater in recuperated offspring (mean ± SEM: 12 ± 2 μm) than in controls (5 ± 0.5 μm) (P < 0.001). This was associated with greater inflammation (interleukin 6: 38% ± 24% increase; P < 0.05; tumor necrosis factor α: 64% ± 24% increase; P < 0.05), lipid peroxidation (4-hydroxynonenal, measured by ELISA: 0.30 ± 0.02 compared with 0.19 ± 0.05 μg/mL per μg protein; P < 0.05), and hyperinsulinemia (P < 0.05). CoQ10 supplementation increased (P < 0.01) hepatic CoQ10 concentrations and ameliorated liver fibrosis (P < 0.001), inflammation (P < 0.001), some measures of oxidative stress (P < 0.001), and hyperinsulinemia (P < 0.01).. Suboptimal in utero nutrition combined with accelerated postnatal catch-up growth caused more hepatic fibrosis in adulthood, which was associated with higher indexes of oxidative stress and inflammation and hyperinsulinemia. CoQ10 supplementation prevented liver fibrosis accompanied by downregulation of oxidative stress, inflammation, and hyperinsulinemia.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cytokines; Diet, Protein-Restricted; Dietary Supplements; Female; Fetal Development; Fetal Growth Retardation; Hepatitis; Hyperinsulinism; Liver; Liver Cirrhosis; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Oxidative Stress; Pregnancy; Pregnancy Complications; Rats, Wistar; Specific Pathogen-Free Organisms; Ubiquinone; Weaning

The lipophilic antioxidant coenzyme Q10 is an effective inhibitor of oxidative damage. Furthermore coenzyme Q10 is involved in electron transport related to the mitochondrial respiratorial chain. Because of this double function coenzyme Q10 has become a special role in the group of antioxidants. Little is known about coenzyme Q10 in healthy and sick children. The aim of the study was to determine the role of coenzyme Q10 in the pathophysiological concept of pediatric diseases. At first a HPLC-method for the detection of coenzyme Q10 in plasma, erythrocytes and platelets was developed and age-related reference values for children were established. Based on these reference values the CoQ10 status was measured in different pediatric diseases. By this way various conditions for low coenzyme Q10 plasma values in children could be defined. Furthermore there were different in vivo models developed to define pharmacokinetic and pharmacodynamic characteristics of coenzyme Q10. The established methods and measured data might be a helpful contribution for estimating coenzyme Q10 deficiency and for planning therapeutical studies with coenzyme Q10 in childhood.

Topics: Antioxidants; Ataxia; Child; Hepatitis; Humans; Migraine Disorders; Mitochondria, Muscle; Mitochondrial Diseases; Oxidative Stress; Severity of Illness Index; Ubiquinone

Oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former and has been suggested to be a relevant factor in aging as well as in different pathological conditions, such as heart attack, diabetes, and cancer. Ubiquinol is very sensitive against oxygen radicals and gives ubiquinone as an oxidation product. Therefore, the ratio of ubiquinol to ubiquinone should be a good marker of oxidative stress because of its definition. A method for the simultaneous detection of ubiquinol-10 and ubiquinone-10 in human plasma is described. Heparinized human plasma was mixed with 5 volumes of methanol and 10 volumes of hexane. After vigorous shaking and centrifugation, the hexane phase (5 microliters) was injected immediately and directly on to reverse-phase HPLC equipped with an on-line reduction column and an electrochemical detector in order to avoid the oxidation of ubiquinol to ubiquinone. It was found that the ratio of ubiquinol-10 to ubiquinone-10 was about 95/5 in human plasma from healthy donors. A significant increase in the oxidized form (ubiquinone-10) content was observed in plasmas of patients with hepatitis, cirrhosis, and hepatoma when compared with normal subjects, suggesting increased oxidative stress in these patients.

Topics: Biomarkers; Carcinoma, Hepatocellular; Chromatography, High Pressure Liquid; Coenzymes; Electrochemistry; Hepatitis; Hexanes; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Solvents; Ubiquinone; Vitamin E