Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that alpha-tocopherol (vitamin E) pretreatment of experimental animals can protect against acute liver necrosis induced by carbon tetrachloride. In this study we investigated whether the increase of vitamin E liver content by dietary supplementation influences chronic liver damage and cirrhosis induced by carbon tetrachloride in the rat. Our data indicate that vitamin E supplementation did not interfere with the growth rate of the animals and increased about threefold the liver's content of the vitamin. Vitamin E supplementation significantly reduced oxidative liver damage, but it was not effective in protecting against development of fatty liver and did not interfere with metabolic activation of carbon tetrachloride. Moreover, vitamin E-fed animals showed incomplete but significant prevention of liver necrosis and cirrhosis induced by carbon tetrachloride. This has been shown by means of histological examination, analysis of serum parameters and biochemical evaluation of collagen content. These results show that an increased liver content of vitamin E can afford a significant degree of protection against carbon tetrachloride-induced chronic liver damage and cirrhosis.
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PMID:Vitamin E dietary supplementation protects against carbon tetrachloride-induced chronic liver damage and cirrhosis. 139 81

The cause of low fertility in dairy cows is multifactorial. Poor nutrition during the dry and early postpartum periods results in reduced glucose, insulin, insulin-like growth factor (IGF-I) and low LH pulse frequency with concomitant increases in beta-hydroxy butyrate, non-esterified fatty acids (NEFA) and triacylglycerol. Cows must mobilize large lipid, but also some protein reserves, with a consequent increased incidence of such metabolic disorders as hypocalcaemia, acidosis, ketosis, fatty liver and displaced abomasums. The occurrence of milk fever and ketosis affects uterine contractions, delays calving and increases the risk of retained foetal membranes (RFM) and endometritis. The nutritional risk factors that cause RFM are hypocalcaemia, high body condition score (BCS) at calving and deficiencies in Vitamin E and selenium. The risk factors for endometritis are hypocalcaemia, RFM, high triacylglycerol and NEFA. Thus, metabolic disorders predispose cows to gynaecological disorders, thereby reducing reproductive efficiency. Cows that are overconditioned at calving or those that lose excess body weight are more likely to have a prolonged interval to first oestrus, thereby prolonging days open. Nutritionally induced postpartum anoestrus is characterized by turnover of dominant follicles incapable of producing sufficient oestradiol to induce ovulation due to reduced LH pulse frequency. High nutrition can also increase metabolic clearance rate of steroid hormones such as progesterone or oestradiol. Lower concentrations of oestradiol on the day of oestrus are highly correlated with the occurrence of suboestrus, thereby making the detection of oestrus in high yielding cows even more difficult. Nutrition also affects conception rate (CR) to AI. Cows that develop hypocalcaemia, ketosis, acidosis or displaced abomasums have lower CRs and take longer to become pregnant. Excessive loss of BCS and excess protein content of the ration can reduce CR while supplemental fats that attenuate the production of F2alpha can improve CR. The increased metabolic clearance rate of progesterone (P4), which decreases blood concentrations during early embryo cleavage up to the blastocyst stage is associated with decreased CRs. In conclusion, poor nutritional management of the dairy cow, particularly before and after calving, is a key driver of infertility.
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PMID:The effect of nutritional management of the dairy cow on reproductive efficiency. 1699 5

Vitamin E (alpha-tocopherol) has demonstrated antioxidant activity and gene-regulatory properties. d-Galactosamine (D-GalN)-induced cell death is mediated by nitric oxide in hepatocytes, and it is associated with hepatic steatosis. The beneficial properties of alpha-tocopherol and their relation to oxidative stress and gene regulation were assessed in D-GalN-induced cell death. Hepatocytes were isolated from human liver resections by a collagenase perfusion technique. alpha-Tocopherol (50 microM) was administered at the advanced stages (10 h) of D-GalN-induced cell death in cultured hepatocytes. Cell death, oxidative stress, alpha-tocopherol metabolism, and NF-kappaB-, pregnane X receptor (PXR)-, and peroxisome proliferator-activated receptor (PPAR-alpha)-associated gene regulation were estimated in the hepatocytes. D-GalN increased cell death and alpha-tocopherol metabolism. alpha-Tocopherol exerted a moderate beneficial effect against apoptosis and necrosis induced by D-GalN. Induction (rifampicin) or inhibition (ketoconazole) of alpha-tocopherol metabolism and overexpression of PXR showed that the increase in PXR-related CYP3A4 expression caused by alpha-tocopherol enhanced cell death in hepatocytes. Nevertheless, the reduction in NF-kappaB activation and inducible nitric oxide synthase expression and the enhancement of PPAR-alpha and carnitine palmitoyl transferase gene expression by alpha-tocopherol may be relevant for cell survival. In conclusion, the cytoprotective properties of alpha-tocopherol are mostly related to gene regulation rather than to antioxidant activity in toxin-induced cell death in hepatocytes.
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PMID:Cytoprotective properties of alpha-tocopherol are related to gene regulation in cultured D-galactosamine-treated human hepatocytes. 1793 89

Nonalcoholic fatty liver disease (NAFLD) is a state of excessive accumulation of fat in the liver of persons whose alcohol intake is lower than the classical level for causing liver damage. When inflammation and fibrosis occur in addition to fatty liver, followed by the development of chronic hepatic dysfunction, the condition is called non-alcoholic steatohepatitis (NASH). Vitamin E possesses antioxidant activity and is effective for NASH, but the mechanism of action is not known. We utilized a methionine-choline deficiency rat model (MCD rats) to investigate the mechanism by which vitamin E improves NASH. In MCD rats, high-dose vitamin E therapy reduced the hepatic content of thiobarbituric acid-reactive substances, but failed to improve liver histopathology. The hepatic content of alpha-tocopherol was also elevated and this might be related to the expression of alpha-tocopherol transfer protein.
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PMID:Children's toxicology from bench to bed--Liver Injury (2): Mechanism of antioxidant therapy for nonalcoholic fatty liver disease. 1957 73

We have previously shown that treatment of steatotic livers with vitamin E succinate decreases liver injury and increases survival after ischemia/reperfusion (I/R). It is now understood that compromised energy status is associated with increased injury following liver ischemia in the setting of hepatic steatosis at least partially as a result of increased reactive oxygen species (ROS) and induction of mitochondrial uncoupling protein-2 (UCP2). Given the association between ROS, mitochondrial function, and UCP2, it was our goal to determine whether the protective effects of vitamin E succinate were associated with decreased ROS injury, down-regulation of UCP2, or improvement of ATP levels following I/R. To test this, leptin deficient (ob/ob) mice with steatotic livers that had received other 50 IU of vitamin E succinate supplement per day or control chow for 7 days were subjected to total hepatic ischemia (15 minutes) followed by reperfusion. We measured liver expressions of ATP, glutathione (GSH), and UCP2 as well as mitochondrial DNA damage. Vitamin E treatment decreased hepatic UCP2 expression and increased ATP and GSH levels prior to I/R. These levels were maintained at 1 hour after I/R. At 24 hours, while hepatic UCP2 expression, ATP, and GSH levels were similar to those of mice not receiving vitamin E, mitochondrial DNA damage was blocked. These results revealed that vitamin E succinate decreased hepatic UCP2 expression, reduced oxidative stress, and improved mitochondrial function in mice with steatotic livers before and after I/R, identifying mechanisms of protection in this setting.
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PMID:Vitamin E succinate enhances steatotic liver energy status and prevents oxidative damage following ischemia/reperfusion. 2000 47

Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease (NAFLD). NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH) is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only limited clinical evidence is available regarding their long-term efficacy and safety. Vitamin D and renin-angiotensin-aldosterone system blockers are promising drugs that are currently being intensively investigated for use in NAFLD/NASH patients.
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PMID:Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options. 2631 17

Oxidative stress and lipid peroxidation have been implicated in the pathogenesis of various diseases, including atherosclerosis and fatty liver diseases, and consequently the role of antioxidants in the prevention and treatment of such diseases has received much attention. In particular, the effects of vitamin E, the most important lipophilic radical-scavenging antioxidant, have been investigated extensively. Many in vitro, animal, and epidemiological studies have reported positive results, but large-scale randomized controlled intervention studies and meta-analyses have produced inconsistent and often disappointing results. In the present review article, the role and action of vitamin E are discussed, with consideration of the factors that determine the outcome of vitamin E treatment. Vitamin E should benefit subjects experiencing oxidative stress due to free radicals when administered at the correct time and for an appropriate duration.
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PMID:Evidence for beneficial effects of vitamin E. 2635 50

Hepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than vitamin E. Here, we compared the effects of astaxanthin and vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese mice. In a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet, astaxanthin alleviated excessive hepatic lipid accumulation and peroxidation, increased the proportion of M1-type macrophages/Kupffer cells, and activated stellate cells to improve hepatic inflammation and fibrosis. Moreover, astaxanthin caused an M2-dominant shift in macrophages/Kupffer cells and a subsequent reduction in CD4(+) and CD8(+) T cell recruitment in the liver, which contributed to improved insulin resistance and hepatic inflammation. Importantly, astaxanthin reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. Overall, astaxanthin was more effective at both preventing and treating NASH compared with vitamin E in mice. Furthermore, astaxanthin improved hepatic steatosis and tended to ameliorate the progression of NASH in biopsy-proven human subjects. These results suggest that astaxanthin might be a novel and promising treatment for NASH.
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PMID:Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E. 2847 50

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition worldwide, and is projected to become the leading cause for liver transplantation in the United States as early as 2020. The mainstay of treatment remains lifestyle modification with diet and exercise recommendations, as although some pharmacological treatments such as glitazones and Vitamin E have shown benefit, there are concerns regarding long term safety. The evidence base for dietary interventions in NAFLD such as the Mediterranean diet, omega-3 polyunsaturated fatty acids and coffee is mainly derived from observational data with questionable validity. Where trials exist, they have shown benefit for surrogate outcomes such as hepatic steatosis and insulin resistance, but no trials have been conducted with salient clinical outcomes such as reduction in progression to chronic liver disease. Benefit in surrogate outcomes has also been seen for aerobic, anaerobic and combined modality exercise but it remains unclear if one type is superior. Furthermore, a reduction in sedentary time appears equally important. To provide a sound evidence base for lifestyle recommendations to people with NAFLD, longer duration trials of standardized dietary or exercise interventions, and testing various doses, types and with liver related outcomes, are essential.
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PMID:Exercise and diet in the management of nonalcoholic fatty liver disease. 2680 14

Following the epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in western countries. NAFLD is the hepatic manifestation of metabolic syndrome and may progress to cirrhosis and hepatocellular carcinoma. To date, there are no approved drugs for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification, including increase of physical activity and the adoption of a healthy eating behavior. In this regard, studies aimed to elucidate the effect of dietary interventions and the mechanisms of action of specific food bioactives are urgently needed. The present review tries to summarize the most recent data evidencing the effects of nutrients and dietary bioactive compounds intake (i.e., long-chain PUFA, Vitamin E, Vitamin D, minerals and polyphenols) on the modulation of molecular mechanisms leading to fat accumulation, oxidative stress, inflammation and liver fibrosis in NAFLD patients.
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PMID:Nutritional therapy for nonalcoholic fatty liver disease. 2689 59


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