Top PDF Alcohol induced liver disease: when fat and oxidative stress meet

Alcohol induced liver disease: when fat and oxidative stress meet

Alcohol induced liver disease: when fat and oxidative stress meet

Annals of Hepatology 2(2) 2003: 69-75 70 Elevated cytokine levels cause symptoms of chronic inflammation. The liver also plays a role in the inflamma- tory response, both as a potential site of chronic inflam- matory diseases as in ALD, and as a source of phagocytes and cytokines. Dysregulated TNF metabolism in ALD was first described more than a decade ago with the ob- servation that cultured monocytes obtained from patients with alcoholic hepatitits spontaneously produced more TNF either under basal conditions and particularly upon LPS challenge. 3,4 The relevance of these pioneering ob- servations in patients has been recognized in animal mod- els, particularly in TNFR-1 knockout mice 5 in which al- cohol-induced liver damage was diminished compared to wild type mice. Moreover, depletion of Kupffer cells, a major source of TNF and other cytokines, prevents liver injury. Thus, the release of TNF overproduction by monocytes and Kupffer cells and its effects on hepato- cytes will impact on the sensitization of the liver to alco- hol. 6 Since TNF is such an important pathogenetic factor in the disease, the characterization of its signaling path- way would be instrumental for the management of ALD.
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Oxidative Stress Modulation by Rosmarinus offi cinalis in CCl4-induced Liver Cirrhosis

Oxidative Stress Modulation by Rosmarinus offi cinalis in CCl4-induced Liver Cirrhosis

Doctorado en Farmacología Médica y Molecular, Unidad Académica de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, Zac., 98000, México. Rosmarinus offi cinalis (Lamiaceae) possesses antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative for chronic liver disease. The effect produced by a methanolic extract of Rosmarinus offi cinalis on CCl 4 -induced liver cirrhosis in rats was investigated using both prevention and reversion models. Over the course of the development of cirrhosis, the increased enzymatic activities of gamma- glutamyl transpeptidase and alanine aminotransferase, and the rise in bilirubin levels caused by CCl 4 adminis- tration, were prevented by Rosmarinus offi cinalis co-administration. When the cirrhosis by oxidative stress was evaluated as an increase on liver lipoperoxidation, total lipid peroxides, nitric oxide in serum, and loss of erythrocyte plasma membrane stability, R. offi cinalis was shown to prevent such alterations. On cirrhotic animals treated with CCl 4 , histological studies showed massive necrosis, periportal infl ammation and fi brosis which were modifi ed by R. offi cinalis. These benefi ts on experimental cirrhosis suggest a potential therapeutic use for R. offi cinalis as an alternative for liver cirrhosis. Copyright © 2009 John Wiley & Sons, Ltd.
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Does oxidative stress induced by alcohol consumption affect orthodontic treatment outcome?

Does oxidative stress induced by alcohol consumption affect orthodontic treatment outcome?

HIGHLIGHTS • Ethanol, Periodontal ligament, Extracellular matrix, Orthodontic movement. Alcohol is a legal drug present in several drinks commonly used worldwide (chemically known as ethyl alcohol or ethanol). Alcohol consumption is associated with several disease conditions, ranging from mental disorders to organic alterations. One of the most deleterious effects of ethanol metabolism is related to oxidative stress. This promotes cellular alterations associated with inflammatory processes that eventually lead to cell death or cell cycle arrest, among others. Alcohol intake leads to bone destruction and modifies the expression of interleukins, metalloproteinases and other pro-inflammatory signals involving GSKβ, Rho, and ERK pathways. Orthodontic treatment implicates mechanical forces on teeth. Interestingly, the extra- and intra-cellular responses of periodontal cells to mechanical movement show a suggestive similarity with the effects induced by ethanol metabolism on bone and other cell types. Several clinical traits such as age, presence of systemic diseases or pharmacological treatments, are taken into account when planning orthodontic treatments. However, little is known about the potential role of the oxidative conditions induced by ethanol intake as a possible setback for orthodontic treatment in adults.
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Fatty liver and abdominal fat relationships with high C reactive protein in adults without coronary heart disease

Fatty liver and abdominal fat relationships with high C reactive protein in adults without coronary heart disease

with FL. 29,30 In physiological conditions, the adi- pose tissue is the main source of free fatty acids for the liver synthesis of triglycerides. However, when the adipose tissue is insulin-resistant, releases ex- cessive amounts of fatty acids that accumulate in the liver along with other compounds such as dia- cylglycerols and ceramides, which trigger proin- flammatory cytokine production. 31,32 Oxidative stress, produced by the lipotoxic effect related to the accumulation of saturated fatty acids in the liv- er, is another inductive factor of inflammation. 33,34 Together, these abnormalities could explain the di- rect and independent link of FL with hs-CRP, and HOMA-IR observed in our study.
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Protective effect of a phytocompound on oxidative stress and DNA fragmentation against paracetamol induced liver damage

Protective effect of a phytocompound on oxidative stress and DNA fragmentation against paracetamol induced liver damage

present study has demonstrated that DTS supplementation actively prevents the severe impairment of membrane- bound ATPase activity and protein thiols which are indeed physiological free radical scavengers. Indeed, profound changes in cell energy metabolism with a marked loss of total ATPase has been observed in animals administered paracetamol alone at whatever dosage in our study, which might be due to the loss of protein SH groups. This impair- ment is due to the alkylation of membrane proteins by re- active paracetamol metabolites. In particular, calcium AT- Pase activity within the plasma membrane which is an im- portant regulating factor to maintain low cytosolic calcium levels and its activity is inhibited by the loss in free sulphydryl groups, whether by alkylation or oxida- tion. This is because the drug-induced limitation of the mitochondria to buffer a non-physiological increase in calcium may lead to the inappropriate stimulation of a number of calcium-activated catabolic enzymes inappro- priate stimulation of a number of calcium-activated cata- bolic enzymes. Thus, intracellular calcium homeostasis is of great importance to cell viability and a variety of toxi- cant-induced hepatocellular injury results in the influx of Ca 2+ into the cell, giving rise to a cascade of toxic events and resulting in cell death. It is suggested that, at low con- centrations, NAPQI induces calcium release mainly via its oxidizing properties, which result in pyridine nucleotide hydrolysis and the stimulation of protein mono ADP ribo- sylation while at high concentrations protein arylation may also be a contributing factor. Although we didn’t ex- amine the whole set of inorganic cations in liver tissue, it appeared that also animal intoxicated with even sub-toxic dosages of paracetamol, show elevated levels of calcium in the liver tissue ( ≥ 60%) and this abnormality was pre- vented when administered with DTS. This overall protec- tive effect may be due to the presence of some antiapop- totic- and (water-soluble) antioxidant-endowed compo- nents 34-37 which may have prevented the excessive oligonucleosomal DNA integrity in the face of paraceta- mol challenge. Besides the direct quenching activity against metabolic activation of reactive metabolites, a pro- tective epigenomic effect modulating the genes responsi- ble for synthesis of antioxidant enzymes and DNA repair is likely to have taken place and it the matter of currently ongoing research. Moreover, a limitation in our present study warranting further research is represented by the need to ascertain whether DTS directly inhibited the me- tabolism of paracetamol to the toxic metabolite NAPQI while caution has to be applied in consideration of possi- ble specie-specific differences too.
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When Phraseology and Ontologies Meet

When Phraseology and Ontologies Meet

According to our knowledge of the domain, the question should be “no”, in order to be completely sure that the right modelling decision is to further model those classes as exhaustive classes. Conclusions In this paper we have tried to show how grammatical collocations can provide interesting hints about the conceptual relations underlying them. In fact, these combinations of lexical items have been used in fields like Terminology and Ontology Engineering with the purpose of automatically extracting data for accelerating respectively terminology tasks and ontology development. However, with this new approach to what we have called Lexico-Syntactic Patterns (LSPs), we aim at applying lexical combinations to help users who are not experts in ontology engineering to develop ontologies by formulating in NL what they want to model. In order to support the system for an automatic identification of LSPs corresponding to ontological relations, we have developed a repository of LSPs associated to ontological relations that make up the core of the system. In this paper, we have focused on those LSPs expressing the "subclass of" ontological relation, and have pointed out the semantic differences between the lexical combinations expressing this relation and the “equivalent” ontological relation, since the latter needs to be further specified with information about disjointness and exhaustiveness. As explained in the paper, some lexical elements may help to directly identify these specifications. Notwithstanding, with the aim of validating and making explicit these properties of the “subclass of” relation, user interaction with the system has been devised. Future work will be centred on enriching this initial repository of LSPs, putting special emphasis on the discovery of disparities between lexical and ontological relations.
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Probiotics in non alcoholic fatty liver disease: which and when

Probiotics in non alcoholic fatty liver disease: which and when

probiotics to prescribe? Another question is when to prescribe? Today, a large range of probiotic prepara- tions is available in supermarkets and health food shops, which can also be available in internet. The global probiotic market generated US $15.9 billion in 2008 and is expected to be worth US$ 32.6 billion by 2014 with a compound annual growth rate of 12.6% from 2009 to 2014. 27 There are drinks, yoghurts, powders and capsules. Powders and capsules have high numbers of bacteria but may lose a variable amount of these during the storage. Milk derivatives often present a lower number of bacteria when they are refrigerated. The use of certain types of bacteria in the probiotic formulations may depend on the his- torical use in foods by that society, even when clini- cal evidence is provided to support it. Such preparations differ greatly for bacterial number ac- cording to species and brand, which is generally >
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Intestinal mucosal proliferation, apoptosis and oxidative stress in patients with liver cirrhosis

Intestinal mucosal proliferation, apoptosis and oxidative stress in patients with liver cirrhosis

Previous studies have shown a close association of liver cirrhosis with oxidative stress. In humans, oxidative stress has been detected in the blood and liver tissue of cirrhotic patients. 24,25 Oxidative stress-mediated hepatic mitochondrial dysfunction has been previously shown in cirrhosis and assess- ment of this parameter via 13C-based breath tests seems to be a promising non-invasive technique for evaluation of liver function. 26 Regarding the intesti- nal mucosa in liver cirrhosis, high levels of oxidati- ve stress have been previously shown in experimental animals. 17,18 To the best our knowled- ge, this is the first study demonstrating the pres- ence of high oxidative stress in the intestinal mucosa of patients with decompensated cirrhosis. In the present study high intestinal mucosa oxidative stress was detected only in patients with decom- pensated cirrhosis, which is in line with previous reports demonstrating high blood oxidative stress in patients with advanced cirrhosis. 27 A potential ex- planation might be the higher levels of systemic en- dotoxemia observed in decompensated disease, which is an important oxidative stress promoter through activation of a systemic inflammatory response, and the depleted hepatocyte antioxidant defenses in advanced liver disease. Potential causes of high intestinal oxidative stress in decompensated cirrhosis are enterocyte mitochondria and increased activity of mucosal xanthine oxidase in conjunction with decreased activity of antioxidant enzymes like xan- thine dehydrogenase, superoxide dismutase and catalase. 17,28
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Effect of sodium tungstate on obesity induced cardiac hypertrophy and oxidative stress

Effect of sodium tungstate on obesity induced cardiac hypertrophy and oxidative stress

Sodium tungstate significantly atten- uated the increase in body weight adiposity index, obesity index, TBARS, SAG and reduced glutathione, whereas no significant change was observed the[r]

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Drug induced fatty liver disease: An overview of pathogenesis and management

Drug induced fatty liver disease: An overview of pathogenesis and management

Overview While the exact mechanisms by which steatosis progresses into steatohepatitis are not clearly delineat- ed, a key role of mitochondrial dysfunction has been proposed. Drugs that impair mitochondrial OXPHOS and MRC have been implicated in the pathogenesis of steatohepatitis. 8,25,43. MRC inhibition not only contrib- utes to fat deposition in hepatocytes but it also has the damaging effect of producing ROS. ROS affect the hepatocytes in different ways. ROS trigger the peroxi- dation of polyunsaturated fatty acids, which in turn activate Kupffer leading to inflammation, and stellate cells, stimulating fibrogenensis. 20,44-46 Stress signaling pathways, nuclear and mitochondrial DNA damage, MRC inhibition and cell death are the end results of the modulatory effects of lipid peroxidation. 47-49 This cell environment in turn leads to mitochondrial dys- function, further augmenting the generation of ROS production and induction of cell death, including the activation of inflammatory cytokines such as TNF-α and TGF-β. 20,50
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Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag- nosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more fre- quently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepa- totoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease
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Oxidative Stress: A Pathogenic Mechanism for Niemann Pick Type C Disease

Oxidative Stress: A Pathogenic Mechanism for Niemann Pick Type C Disease

Copyright © 2012 Mary Carmen V´azquez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Niemann-Pick type C (NPC) disease is a neurovisceral atypical lipid storage disorder involving the accumulation of cholesterol and other lipids in the late endocytic pathway. The pathogenic mechanism that links the accumulation of intracellular cholesterol with cell death in NPC disease in both the CNS and the liver is currently unknown. Oxidative stress has been observed in the livers and brains of NPC mice and in different NPC cellular models. Moreover, there is evidence of an elevation of oxidative stress markers in the serumof NPC patients. Recent evidence strongly suggests that mitochondrial dysfunction plays an important role in NPC pathogenesis and that mitochondria could be a significant source of oxidative stress in this disease. In this context, the accumulation of vitamin E in the late endosomal/lysosomal compartments in NPC could lead to a potential decrease of its bioavailability and could be another possible cause of oxidative damage. Another possible source of reactive species in NPC is the diminished activity of different antioxidant enzymes. Moreover, because NPC is mainly caused by the accumulation of free cholesterol, oxidized cholesterol derivatives produced by oxidative stress may contribute to the pathogenesis of the disease.
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Wine pomace product modulates oxidative stress and microbiota in obesity high fat diet fed rats

Wine pomace product modulates oxidative stress and microbiota in obesity high fat diet fed rats

A B S T R A C T Obesity is associated with in fl ammation and oxidative stress. Bioactive compounds can decrease obesity-related disorders by their antioxidant and anti-in fl ammatory actions. Wistar rats were fed with a high-fat diet during 14 weeks and received 100 mg of wine pomace product (WP)/kg body weight, from the 1st week or from the 7th week and standard diet fed rats were included. Food intake, body weight, blood pressure and plasma glucose, cholesterol and triglyceride were weekly measured. Antioxidant and lipid liver status, fat, adipocyte size, plasma interleukins and microbiota were also determined at 14th week. The results showed a significant reduction of body weight and abdominal fat area, lower blood glucose, decreased liver weight and lipids deposition with increased antioxidant status, lower adipocyte size and increased Lactobacillus spp./Bacteroides spp. ratio.
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Contribution of Oxidative Stress and Inflammation to the Neurogenic Hypertension Induced by Intermittent Hypoxia

Contribution of Oxidative Stress and Inflammation to the Neurogenic Hypertension Induced by Intermittent Hypoxia

The CBs denervation and the pharmacological inhibition of the SFO produced a partial reduction of RSO, while combined CB denervation and SFO inhibition eliminated the increased sympathetic overactivity following intermittent hypoxia. Thus, the evidence suggests that SFO mediates the effects of elevated circulating levels of Ang II. Proinflammatory cytokines plays a key role in hypertension, but these molecules do not permeate the blood–brain barrier. Thus, it has been proposed that the CVOs mediate the hypertensive effects of circulating pro-inflammatory cytokines. Wei et al. (2013) found that the increased BP and RSA elicited by the intracarotid injection of TNF- α and IL- 1 β was attenuated in SFO-lesioned rats. They found that the increased BP and RSO induced by injections of TNF-α or IL- 1 β into the rat SFO were attenuated by microinjections of losartan and captopril in the SFO (Wei et al., 2015). More recently, Wei et al. (2018) found that the intravenous injection of IL-1 β increased mRNA levels of the angiotensin-converting enzyme, AT1R, TNF-α, and IL-1β in the SFO and the PVN.
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Enalapril effects on nitric oxide synthase inhibition-induced hypertension: hemodynamic and oxidative stress evaluations

Enalapril effects on nitric oxide synthase inhibition-induced hypertension: hemodynamic and oxidative stress evaluations

These results suggest that L-NAME administration in- creased arterial pressure and oxidative stress, indicating glutathione peroxidase as an important antioxi- dant in this model..[r]

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Is intestinal oxidative stress involved in patients with compensated liver cirrhosis?

Is intestinal oxidative stress involved in patients with compensated liver cirrhosis?

These findings may point to an enhancement of repair proc- esses for oxidative stress. In the sigmoid mucosa, gene tran- scription of GR as well as GS, the latter being one of the enzymes involved in the synthesis of GSH, was down-regu- lated in cirrhotic patients, which might indicate a decreased formation of GSH. However, protein levels of GSH, GSSG and the GSH/GSSG ratio were not altered. It should be noted that the differences in gene transcription in both duo- denum and sigmoid did not remain statistically significant after correcting for multiple testing and therefore should be interpreted with care. In addition, no alterations were found for the other genes investigated. Thereby the above findings indicate that there is no clear evidence for oxida-
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S adenosylmethionine metabolism and liver disease

S adenosylmethionine metabolism and liver disease

REGULATION OF HEPATIC SAME CONTENT Due to the importance of SAMe as a regulator of multiple hepatic functions, the hepatic content of SAMe must be maintained constant independently of the daily intake of methionine, or of the ingest of betaine and choline, the only two dietary compounds that can supply the methyl group for methionine synthesis, or of the endogenous synthesis of 5-MTHF. Thus, when the hepatic content of methio- nine is high, this amino acid is rapidly converted to SAH due to the concerted action of MATIII and GNMT, which are activated by methionine and SAMe respectively, and then to homocysteine by AHCY (Figure 1). Moreover, SAMe activates CBS and inhibits MTHFR, and consequently the synthe- sis of 5-MTHF, the substrate of MS and an inhibitor of GNMT. This way, SAMe controls the flow of ho- mocysteine into the transsulfuration and remethyla- tion pathways, so that when it is high homocysteine is channeled through the transsulfuration pathway, to form cysteine and α-ketobutyrate, and when it is low is used to form methionine and regenerate SAMe.
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Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside

Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside

Oxidative stress, which is the result of an excess of ROS over the antioxidant defenses of the organism, and the free radicals attack lipids, proteins and DNA. These reactions are mainly produced through abstraction of hydrogen atom from target molecules resulting frequently in initiation of chain processes. Control of ROS steady-state level is provided not only via their production, but also via elimination. Organ- isms possess antioxidant system useful to inactivate ROS, or to eliminate them, minimizing or preventing their negative effects. Efficient molecular strategies were evolved in cells that allow to keep the intracellular ROS level under control, and to maintain the balance between oxidant and antioxidant molecules. 8 The effects of ROS/RNS are counteracted by enzymatic and non-enzymatic antioxidant mechanisms. Anti- oxidant molecules eliminate free radicals from the body.
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Effect of Glycine on Lead Mobilization, Lead Induced Oxidative Stress, and Hepatic Toxicity in Rats

Effect of Glycine on Lead Mobilization, Lead Induced Oxidative Stress, and Hepatic Toxicity in Rats

LPO in kidney and liver tissues. GSH levels were decreased in rats exposed to lead. We found that glycine therapy was e ff ective in mitigating all of the e ff ects of lead on parameters indicative of oxidative stress. These findings were equally observed at the three doses evaluated. On the other hand, one of the most important physiological functions of GSH is to protect the thiol groups located on some proteins and enzymes such as ALAD from oxidizing [27]. Although the three glycine treatments resulted in a significant increase in GSH levels, we did not observe reactivity of ALAD. We believe that the high levels of lead in blood in all groups treated may also explain the lack of reactivity of ALAD.
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Mitogen activated protein kinases are involved in hepatocanalicular dysfunction and cholestasis induced by oxidative stress

Mitogen activated protein kinases are involved in hepatocanalicular dysfunction and cholestasis induced by oxidative stress

15 min before tBuOOH. Data are expressed as mean ± S.E.M. a Significantly different from control; b Significantly different from tBuOOH (p < 0.05, n = 5). FIGURE 6. Prevention by MAPK inhibitors of Bsep/Mrp2 endocytic internalization and F-actin cytoskeleton disruption induced by tBuOOH in PRL experiments. Representative confocal images illustrating the endocytic internalization of Bsep and Mrp2, together with the disruption of F-actin cytoskeleton induced by tBuOOH (75 µM, 10 min), and its prevention by the ERK1/2 inhibitor PD098059 (PD, 5 µM), the JNK1/2 inhibitor SP600125 (SP, 1 µM), or the p38 MAPK inhibitor SB203580 (SB, 250 nM), administered 15 min before tBuOOH (or DMSO in controls). Images were taken 20 min after the onset of perfusion with tBuOOH. (A) Co-staining of Bsep (green) and F-actin (red); (B) Co-staining of Mrp2 (green) and F-actin (red). In control livers, both Bsep and Mrp2 were mainly confined to the canalicular space, whereas in livers treated with tBuOOH, relocalization of intracellular fluorescence associated with both Bsep and Mrp2 from the canalicular space to the pericanalicular area was apparent, thus indicating endocytic internalization of the transporters. The MAPK inhibitors prevented this phenomenon, as illustrated by a control- like pattern of the Bsep and Mrp2 distribution in livers preperfused with the MAPK inhibitors. Regarding cytoskeleton integrity, pericanalicular localization of F-actin was evident in control livers, while a severe disarrangement of F-actin was observed in livers perfused with tBuOOH. MAPK inhibitors partially prevented tBuOOH-induced disturbances on F-actin cytoskeleton, thus explaining their protective effects on canalicular transporter localization and function.
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