In situ detection of oxidized n-3 polyunsaturated fatty acids in chronic hepatitis C: correlation with hepatic steatosis

Kitase, Akira; Hino, Keisuke; Furutani, Takakazu; Okuda, Michiari; Gondo, Toshikazu; Hidaka, Isao; Hara, Yuichi; Yamaguchi, Yoshiyuki Y.; Okita, Kiwamu

doi:10.1007/s00535-005-1596-x

Cited by 35 publications

(30 citation statements)

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“…The immunohistochemical evidence of HEL presence in atherosclerotic lesions of humans [19], cholesterol-fed rabbits [9] and lipopolysaccharide-induced liver injury in D-galactosamine-sensitized mice [33] has already been reported. 4-HHE-modified protein immunoreactivity was localized in liver of patients with chronic hepatitis C [23], spinal cords from patients with amyotrophic lateral sclerosis [39], in human atherosclerotic aorta [34] and intense light-exposed rat retina [40]. CRA-lysine has been immunohistochemically detected in spinal cord of ALS patients [38] and Alzheimer's disease brain [21].…”

Section: Resultsmentioning

confidence: 99%

“…These timecourse changes of areas positively immunostained for Bax and these oxidation markers are dependent on the development of necrosis in APAP-induced liver injury. DISCUSSION PRL, HEL, 4-HHE-modified protein and CRA-lysine has been immunohistochemically detected in diverse pathological situations in humans [19,21,23,38,39,44] and experimenta l anima ls [9,15,33,40]. PRL has been immunohistochemically detected in atherosclerotic lesions of hypercholesterolemic rabbits [15].…”

Section: Resultsmentioning

confidence: 99%

“…Recently, polyunsaturated fatty acid (PUFA) oxidation markers, such as N ε -propanoyl-modified lysine (PRL), N ε -hexanoyl-modified lysine (HEL) 4-hydroxyhexenal-modified histidine (4-HHE-histidine) and crotonaldehyde-modified lysine (CRA-lysine), have been given more attention as factors related to the processes of diverse pathological situations [9,15,19,21,23,33,[38][39][40]44]. PUFA is easily peroxidized by free radicals and enzymes, and peroxidation of PUFA results in compromised integrity of cellular membranes and leads to lipid hydroperoxide as a major reaction product, and lipid hydroperoxide is decomposed into aldehyde [20].…”

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confidence: 99%

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Immunohistochemical Detection of Polyunsaturated Fatty Acid Oxidation Markers in Acetaminophen-Induced Liver Injury in Rats

Sun

Sugiyama

Hisaka

et al. 2012

The Journal of Veterinary Medical Science

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ABSTRACT. To clarfity whether polyunsaturated fatty acid (PUFA) oxidation is involved in the mechanism of acetaminophen (APAP)-induced apoptotic cell death, the production and localization of PUFA oxidation markers N  -propanoyl-modified lysine, N  -hexanoylmodified lysine, 4-hydroxyhexenal-modified histidine and crotonaldehyde-modified lysine were evaluated in the development of APAPinduced liver injury. The immunoexpression of these markers in the liver was examined up to 24 hr post-APAP intraperitoneal injection in rats (1 g/kg body weight). The histopathological changes in the liver appeared 3 hr after APAP injection and became exacerbated with time. Proapoptotic protein Bax immunoreactivity was first detected in the degenerative hepatocytes 3 hr after the injection and areas positively immunostained for Bax reached a peak level at 6 hr, and then decreased at 12 and 24 hr. There was a significant increase in the TUNEL-positive rate at 12 and 24 hr. Immunohistological expression of all these oxidation markers was first detected in the degenerative hepatocytes 3 hr after the injection, and earlier than the occurrence of hepatocyte apoptosis. Immunohistochemical expression of these markers were observed in almost all degenerative hepatocytes 3-24 hr after APAP injection. Areas positively immunostained for these markers reached a peak level at 6 hr, and then decreased at 12 and 24 hr. The results thus suggest that the generation of PUFA oxidation markers may be the signature of early events preceding the induction of liver cell apoptosis and thus useful for early detection of oxidative stress-related liver cell injury.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Immunohistochemical Detection of Polyunsaturated Fatty Acid Oxidation Markers in Acetaminophen-Induced Liver Injury in Rats

Sun

Sugiyama

Hisaka

et al. 2012

The Journal of Veterinary Medical Science

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“…No entanto, a participação desse mecanismo de lesão, via esteatose hepática, à semelhança do que ocorre na DHGNA, não parece explicar todo o quadro. Enquanto em alguns estudos a esteatose, e não a RI, esteve independentemente associada à fibrose (15) e alguns estudos de imunoistoquímica associarem a positividade de marcadores teciduais de estresse oxidativo com a presença de esteatose (34) , em outros trabalhos, como no publicado por MUZZI et al (46) , a fibrose hepática esteve associada à RI, mas não foi observada relação da fibrose com a esteatose hepática. Esses últimos achados estariam mais de acordo com estudos dos presentes autores, que demonstram que os marcadores séricos de estresse oxidativo na hepatite C crônica estão alterados naqueles pacientes com resistência insulínica, independentemente da presença de esteatose hepática (48) .…”

Section: Ri E Fibrose Hepáticaunclassified

Importância da resitência insulínica na hepatite C crônica

Parise

Oliveira

2007

Arq. Gastroenterol.

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RESUMO -Objetivo -Revisar a importância da resistência insulínica no desenvolvimento da hepatite C crônica e sua interferência na resposta ao tratamento antiviral de pacientes infectados pelo vírus da hepatite C. Fonte de dados -Revisão bibliográfica de trabalhos publicados pelo MEDLINE e dados dos próprios autores. Síntese de dados -Nos últimos anos, grande número de publicações tem demonstrado importante associação entre resistência insulínica e hepatite C crônica. Aumento na prevalência de diabetes mellitus tipo 2, desenvolvimento de esteatose hepática (principalmente nos pacientes com infecção pelo genótipo não-3), progressão mais rápida da doença e redução na taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina, têm sido todos associados à presença de resistência insulínica nos pacientes infectados pelo vírus da hepatite C. A produção aumentada de fator de necrose tumoral pelo core do vírus da hepatite C é o principal mecanismo responsável pelo aparecimento da resistência insulínica. O fator de necrose tumoral afetaria a fosforilação do substrato do receptor de insulina diminuindo a captação de glicose e acarretando hiperinsulinemia compensatória. Aumento da siderose hepática e alterações dos níveis circulantes das adipocitocinas podem ter efeito adicional sobre a sensibilidade à insulina na hepatite C crônica. Conclusões -O diagnóstico e o tratamento da resistência insulínica nesses pacientes podem não só evitar o aparecimento das complicações, mas também prevenir a progressão da doença e, possivelmente, aumentar a taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina. DESCRITORES -Hepatite C crônica. Fígado gorduroso. Cirrose hepática. Resistência à insulina. Diabetes mellitus tipo 2. Interferons.A resistência à ação da insulina tem papel fundamental no aparecimento da síndrome metabólica. No tecido periférico dependente de insulina, ocorre um defeito intracelular pós-receptor na sinalização da insulina (Figura 1). Há bloqueio na fosforilação em tirosina dos substratos protéicos dos receptores de insulina (IRS), o que impede a transativação do GLUT 4 e, conseqüentemente, a entrada da glicose para o interior da célula. Isso faz com que maiores quantidades de insulina sejam secretadas pelas células β pancreáticas, criando um estado de hiperinsulinemia compensatória. Esse excesso de insulina resultante consegue, durante certo tempo, manter a glicemia dentro dos níveis da normalidade, mas acaba determinando importantes alterações em todo organismo. A mais conhecida é a extensiva deposição centrípeta da gordura corporal, conhecida como obesidade central ou visceral, onde ocorre grande aumento da gordura abdominal, em detrimento dos membros. Outros efeitos incluem o aumento da pressão arterial e dos níveis séricos de triglicérides e redução dos valores de HDL colesterol, com ou sem hiperglicemia. A presença de três ou mais dessas manifestações caracteriza a síndrome metabólica ou síndrome de resistência insulínica (64,72) .O estudo da re...

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“…Modifications of DNA or proteins may be repaired, or they are removed through degradation (11). Patients suffering from various forms of liver disease, including nonalcoholic fatty liver disease (12,13) and chronic hepatitis C with steatosis (14), show a marked decrease in the level of polyunsaturated fatty acids (PUFAs) and an increase in the products of lipid peroxidation (12,13).…”

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Inactivation of human liver bile acid CoA:amino acid N-acyltransferase by the electrophilic lipid, 4-hydroxynonenal

Shonsey

Eliuk

Johnson

et al. 2008

Journal of Lipid Research

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The hepatic enzyme bile acid CoA:amino acid N-acyltransferase (BAT) catalyzes the formation of amino acid-conjugated bile acids. In the present study, protein carbonylation of BAT, consistent with modification by reactive oxygen species and their products, was increased in hepatic homogenates of apolipoprotein E knock-out mice. 4-Hydroxynonenal (4HNE), an electrophilic lipid generated by oxidation of polyunsaturated long-chain fatty acids, typically reacts with the amino acids Cys, His, Lys, and Arg to form adducts, some of which (Michael adducts) preserve the aldehyde (i.e., carbonyl) moiety. Because two of these amino acids (Cys and His) are members of the catalytic triad of human BAT, it was proposed that 4HNE would cause inactivation of this enzyme. As expected, human BAT (1.6 mM) was inactivated by 4HNE in a dose-dependent manner. To establish the sites of 4HNE's reaction with BAT, peptides from proteolysis of 4HNE-treated, recombinant human BAT were analyzed by peptide mass fingerprinting and by electrospray ionizationtandem mass spectrometry using a hybrid linear ion trap Fourier transform-ion cyclotron resonance mass spectrometer. The data revealed that the active-site His (His362) dosedependently formed a 4HNE adduct, contributing to loss of activity, although 4HNE adducts on other residues may also contribute.

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In situ detection of oxidized n-3 polyunsaturated fatty acids in chronic hepatitis C: correlation with hepatic steatosis

Abstract: HHE-protein adducts, which are a good marker for oxidative stress, are associated with steatosis in chronic hepatitis C.

Cited by 35 publications

References 33 publications

Immunohistochemical Detection of Polyunsaturated Fatty Acid Oxidation Markers in Acetaminophen-Induced Liver Injury in Rats

Immunohistochemical Detection of Polyunsaturated Fatty Acid Oxidation Markers in Acetaminophen-Induced Liver Injury in Rats

Importância da resitência insulínica na hepatite C crônica

Inactivation of human liver bile acid CoA:amino acid N-acyltransferase by the electrophilic lipid, 4-hydroxynonenal

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