Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial function and structure in cirrhotic livers from humans or rats show a variety of changes as compared to control livers. Mitochondrial ATP production is reduced in rats with CCl4- or thioacetamide-induced liver cirrhosis and in rats with secondary biliary cirrhosis. Activity of the electron transport chain is decreased in rats with secondary biliary cirrhosis. In rats with CCl4-induced cirrhosis, the mitochondrial content of certain constituents of the respiratory chain (cytochrome a + a3, cytochrome b and ubiquinone) is increased and activities of cytochrome c oxidase and ATPase are elevated. Similarly, in humans with liver cirrhosis, mitochondrial cytochrome a + a3 content is elevated and has been used to assess the risk for hepatectomy. In rats with secondary biliary cirrhosis, compensatory strategies include increased mitochondrial volume per hepatocyte and possibly increased extramitochondrial ATP production (increased glycolysis). Thus, a variety of adaptive mechanisms are used to maintain mitochondrial function in cirrhotic livers.
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PMID:Adaptation of mitochondrial metabolism in liver cirrhosis. Different strategies to maintain a vital function. 129 65

Ubiquinone (CoQ10 coenzyme) is part of the respiratory chain in mitochondria, and acts as a scavenger in oxidative stress in cell membranes. Ubiquinone is mainly synthesized in the liver and partly derived from the diet; its plasma levels significantly correlate with tissue levels in experimental animals and in pathological states in man. By means of an original high-performance liquid chromatography technique, we measured ubiquinone plasma levels in 10 healthy subjects, in 27 patients with cirrhosis and in 22 chronic alcoholics with normal liver function. Ubiquinone levels were markedly reduced in cirrhosis (0.25 [SD 0.21] microgram/ml vs. 0.92 [0.38] in controls; P < 0.001), without any difference between alcohol- and non-alcohol-related disease. Also, in chronic alcoholics ubiquinone levels were nearly halved (0.49 [0.24]). In cirrhosis, ubiquinone plasma levels significantly correlated with cholesterol (P < 0.05), and with total bilirubin levels (P < 0.01). Our study highlights a remarkable deficiency in ubiquinone levels in patients with cirrhosis and in chronic alcoholics, to which both reduced hepatic synthesis and nutritional defects may contribute.
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PMID:Reduced ubiquinone plasma levels in patients with liver cirrhosis and in chronic alcoholics. 807 93

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.
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PMID:Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. 926 9

Defects of the respiratory chain are a typical feature of mitochondrial diseases and occur also during normal aging where they have been described in postmitotic tissues. The present study addresses the question of defect expression in the normal and cirrhotic liver. Randomly distributed defects of complex III (ubiquinone-cytochrome-c-oxidoreductase) and of complex IV (cytochrome-c-oxidase) of the respiratory chain have been detected with age-related increasing frequency both in normal and cirrhotic livers. No defects were present for complex II (succinate-dehydrogenase) and complex V (adenosine triphosphate-synthase) and in liver cell carcinomas. Sixty-one of 107 normal livers (57%) showed defects of the respiratory chain. The defects occurred in advanced age (over 50 years) in 87%. In contrast 50 of 64 cirrhotic livers (78%) had defects and approximately 60% occurred after age 50. The defects were caused by a loss of enzyme protein involving both nuclearly and mitochondrially coded subunits. Ninety-four percent of the defects (n = 275) involved complex IV selectively. In 4% selective defects of complex III were found and combined defects of both complexes occurred in only 2%. In situ hybridization and polymerase chain reaction (PCR) studies for the detection of the common deletion (4.977 bp) and of various point mutations of mitochondrial DNA (mtDNA) revealed no consistent molecular genetic abnormalities in microdissected respiratory chain defective liver cell areas. Single point mutations at nt 3243 and/or 5692 were found only in 7 of 18 microdissected probes from 6 patients. The results show that defects of the respiratory chain occur already in normal livers most probably during cell aging and at a higher rate in cirrhosis. The random defect pattern favors a stochastic process, e.g., free radical damage. However, the role of mutations of mtDNA remains to be established.
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PMID:Defects of the respiratory chain in the normal human liver and in cirrhosis during aging. 930 2

We have applied our method for the simultaneous detection of plasma ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form) (S. Yamashita and Y. Yamamoto, Anal. Biochem. 250, 66-73, 1997) to plasmas of normal subjects (n = 16) and patients with chronic active hepatitis (n = 28), liver cirrhosis (n = 16), and hepatocellular carcinoma (n = 20) to evaluate the pressure of oxidative stress in these patients. The average ubiquinone-10 percentages (+/- S.D.) in total ubiquinone-10 and ubiquinol-10 in the four groups were 6.4 +/- 3.3, 12.9 +/- 10.3, 10.6 +/- 6.8, and 18.9 +/- 11.1, respectively, indicating a significant increase in ubiquinone-10 percentage in patient groups in comparison to normal subjects. These results and a significant decrease in the plasma ascorbate level in patient groups indicate that oxidative stress is evident after the onset of hepatitis and the subsequent cirrhosis and liver cancer.
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PMID:Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. 963 73

To assess the degree of oxidative stress, we measured plasma ubiquinone-10 percentage (%CoQ-10) in total amounts of ubiquinone-10 in patients with chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma, and in age-matched control subjects, %CoQ-10 values were 12.9 +/- 10.3 (n = 28), 10.6 +/- 6.8 (n = 28), 18.9 +/- 11.1 (n = 20), and 6.4 +/- 3.3 (n = 16), respectively, showing a significant increase in oxidative stress in patient groups as compared to control subjects. There were no differences in total amounts of ubiquinone-10 and ubiquinol-10 among the four groups. We next measured %CoQ-10 in plasmas obtained from nine patients treated with percutaneous transluminal coronary angioplasty (PTCA). Plasmas were collected when hospitalized, and at the time (0, 4, 8, 12, 16, and 20 hr, and 1, 2, 3, 4, and 7 days) after the PTCA. %CoQ-10 values before and right after PTCA were 9.9 +/- 2.8 and 11.4 +/- 2.0, respectively, reached a maximum (20-45) at 1 or 2 days later, and decreased to 7.9 +/- 2.7 at 7 days after PTCA, indicating an increase in oxidative stress in patients during coronary reperfusion.
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PMID:Plasma ubiquinone to ubiquinol ratio in patients with hepatitis, cirrhosis, and hepatoma, and in patients treated with percutaneous transluminal coronary reperfusion. 1041 36

The role of the isoprenoid pathway in gastrointestinal and hepatic diseases, and its relation to hemispheric dominance, was assessed in this study. The following parameters were measured in patients with (i) acid peptic disease, (ii) ulcerative colitis, (iii) gallstones, (iv) cryptogenic cirrhosis liver, (v) Reye's syndrome, (vi) mesenteric artery occlusion, (vii) irritable bowel syndrome, and (viii) in individuals with right hemispheric, left hemispheric, and bihemispheric dominance: 1. plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; 2. tryptophan/tyrosine catabolic patterns; 3. free radical metabolism; 4. glycoconjugate metabolism; and 5. membrane composition. In patients with gastrointestinal and hepatic disease there were elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. The RBC membrane Na(+)-K+ ATPase activity and serum magnesium were decreased. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites in the serum. There was an increase in cholesterol: phospholipid ratio and a reduction in the glycoconjugate level of RBC membrane in these groups of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. An upregulated isoprenoid pathway and hyperdigoxinemia is characteristic of gastrointestinal and hepatic disease and in right hemispheric chemical dominance. Right hemispheric chemical dominance is important in deciding the predisposition to gastrointestinal and hepatic disease.
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PMID:Hypothalamic digoxin, cerebral chemical dominance, and regulation of gastrointestinal/hepatic function. 1269 Oct 2

The mammalian isoprenoid synthesis pathway (also known as the mevalonate pathway) is fundamental to the metabolism and health of organisms, with products such as cholesterol (sterol isoprenoid), ubiquinone (coenzyme Q) and dolichol (non-sterol isoprenoids) having great importance to mammalian biology and physiology. Targeting the isoprenoid pathway results in novel therapeutic options for a diverse range of conditions. Plant polyprenols are biologically active molecules that affect the isoprenoid pathway - toxic side effects have never been observed during treatment with our pharmaceuti- cal-grade polyprenols (Ropren*). Statins and bisphosphonates also act on this pathway but have the disadvantage of causing numerous side effects. Our unique ability to produce Ropren' containing not less than 95% pure polyprenols has enabled their clinical use in Russia for around eight years and has also enabled researchers to conduct trials into other therapeutic uses. Although polyprenols can treat conditions such as viral, bacterial and fungal infections, inflammation and other immune conditions, this paper focuses on the new pre-clinical and clinical effects of polyprenols in hepatic and neurological conditions. Recent pre-clinical studies have shown treatment with polyprenols from conifers had a range of neurological and cognitive effects, including improved cognitive performance in a rat model relevant to Alzheimer's disease and healthy levels of myelination in mice with an experimental model of multiple sclerosis. Early clinical data has shown Ropren' treatment improved antioxidant levels in people with diabetes and improved liver function in patients on chemotherapy treatment. Ropren' also had positive effects on electroencephalograms of people with alcohol-induced cirrhosis and Alzheimer's disease and significantly decreased symptoms in people with depression. These results pave the way for larger clinical trials and show how Ropren' is a valuable clinical tool to treat a wide range of liver and neurological conditions.
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PMID:NEW HEPATIC AND NEUROLOGICAL CLINICAL IMPLICATIONS OF LONG-CHAIN PLANT POLYPRENOLS ACTING ON THE MAMMALIAN ISOPRENOID PATHWAY. 2988 54