Oxidative stress in the development of liver cirrhosis: A comparison of two different experimental models

Natarajan, Sathish Kumar; Thomas, Simmy; Ramamoorthy, Prabhu; Basivireddy, Jayasree; Pulimood, Anna; Ramachandran, Anup; Balasubramanian, K.A.

doi:10.1111/j.1440-1746.2006.04231.x

Cited by 107 publications

(86 citation statements)

References 48 publications

(44 reference statements)

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“…A similar trend was seen in TAA-treated rats. 15 The serum enzymes and liver hydroxyproline remained elevated even after 5 months of treatment, indicating that in this model, frank cirrhosis was established by 3 months of treatment and sustained at 5 months of treatment.…”

Section: Resultsmentioning

confidence: 91%

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Renal damage in experimentally-induced cirrhosis in rats: Role of oxygen free radicals

et al. 2006

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Cirrhosis with ascites is associated with impaired renal function accompanied by sodium and water retention. Although it has been suggested that mediators such as nitric oxide play a role in the development of renal failure in this situation, other mechanisms underlying the process are not well understood. This study examined the role of oxidative stress in mediating renal damage during the development of cirrhosis in order to understand mechanisms involved in the process. It was shown that carbon tetrachloride-or thioacetamide-induced cirrhosis in rats results in oxidative stress in the kidney as seen by increased lipid peroxidation and protein oxidation, accompanied by altered antioxidant status. Cirrhosis was also found to affect renal mitochondrial function, as assessed by measurement of the respiratory control ratio, the swelling of mitochondria, and calcium flux across mitochondrial membranes. Increased lipid peroxidation and changes in lipid composition were evident in the renal brush border membranes, with compromised transport of 14 C glucose across these membranes. In conclusion, renal alterations produced as a result of cirrhosis in the rat are possibly mediated by oxidative stress. (HEPATOLOGY 2006;43:1248-1256

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Section: Resultsmentioning

confidence: 91%

“…Control rats received the vehicle alone. 15 Animals were sacrificed after 1, 2, 3, 4, or 5 months of CCl 4 or TAA treatment. For each treatment period, TAA-treated animals were sacrificed 1 week after stopping treatment, and CCl 4 -treated animals were sacrificed 10 days after stopping phenobarbitone.…”

Section: Methodsmentioning

confidence: 99%

Renal damage in experimentally-induced cirrhosis in rats: Role of oxygen free radicals

et al. 2006

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“…Like various other hepatotoxins, hepatotoxicity of CCl 4 is mediated by oxidative damage through metabolic activation, producing free radicals and leading to lipid peroxidation, DNA damage, and cellular death. 33,34,37,38 The generation of high levels of ROS by CCl 4 not only results in tissue damages but continues to exert effects on the transplanted cells. Our data showing superior resistance of MSCs to oxidative stress in vitro and in vivo seems to find support from studies reporting the persistence of MSCs in patients after myeloablation 39 and is coherent with the recipient survival curves.…”

Section: Discussionmentioning

confidence: 99%

Stem Cell Therapy for Liver Disease: Parameters Governing the Success of Using Bone Marrow Mesenchymal Stem Cells

Kuo¹,

et al. 2008

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Background & Aims-Liver transplantation is the primary treatment for various end-stage hepatic diseases but is hindered by the lack of donor organs and by complications associated with rejection and immunosuppression. There is increasing evidence to suggest the bone marrow is a transplantable source of hepatic progenitors. We previously reported that multipotent bone marrow-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells with almost 100% induction frequency under defined conditions, suggesting the potential for clinical applications. The aim of this study was to critically analyze the various parameters governing the success of bone marrow-derived mesenchymal stem cell-based therapy for treatment of liver diseases.

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“…Em uma visão geral, considera-se como vantagem na indução por CCl 4 sua correlação com a cirrose hepática em relação às questões morfofisiopatológicas, como a insuficiência hepática obtida (Zim et al, 2002;Natarajan et al, 2006). Entretanto, desvantagens, como a presença de septos fibrosos, pouca proliferação ductobiliar e rápida regressão das lesões dificultam o estudo de tratamentos anticirróticos em longo prazo (Cremonese et al, 2001;Li et al, 2002;Muriel e Escobar, 2003), devido à baixa reprodutibilidade e homogeneidade do quadro cirrótico (Laleman et al, 2006) e alto índice de mortalidade encontrados durante a indução (Jeong et al, 2001;Li et al, 2002;Laleman et al, 2006;Lee et al, 2008).…”

Section: Análise Comparativa Dos Modelos Cirróticos: Vantagens E Desvunclassified

<b>Modelos experimentais para indução de cirrose hepática em animais: Revisão de literatura</b><br>doi: 10.5007/2175-7925.2010v23n2p183

et al. 2011

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ResumoO fígado desempenha papel homeostático fundamental no equilíbrio de numerosos processos biológicos. Cirrose hepática é uma síndrome, na qual convergem algumas doenças hepáticas crônicas, ocorrendo lesão hepatocelular seguida de deposição exacerbada de tecido fibroso ocasionando desorganização da arquitetura tecidual. O fígado está sujeito à lesão potencial por uma grande quantidade de agentes farmacológicos, tóxicos e/ou microbiológicos. Para o estudo de possíveis tratamentos para a cirrose, é necessário o estabelecimento de modelos animais de indução de cirrose, principalmente em roedores de laboratório que mimetizem o processo cirrótico encontrado em animais e homem, que tenham alta reprodutibilidade, homogeneidade e baixa mortalidade. Sendo assim, a indução de cirrose hepática torna-se primordial para investigar doenças hepáticas crônicas, como também para testar possíveis tratamentos terapêuticos para posterior utilização na clínica veterinária e humana. Tetracloreto de Carbono-CCl 4 , Tiocetamida -TAA e Dimetilnitrosamina -DMN têm sido as drogas de eleição para a indução da cirrose experimental em ratos, e são os modelos analisados neste trabalho. O modelo cirrótico com a TAA se mostrou ser o mais promissor pelos seguintes motivos: produz padrão histológico mais próximo ao da cirrose humana, com menor mortalidade, maior reprodutibilidade e segurança, apesar do período de indução ser maior (14 semanas).Unitermos: cirrose hepática, indução, modelos experimentais, rato, tioacetamida AbstractExperimental models for induction of liver cirrhosis in animals: a review. The liver plays a key role in the homeostatic balance of many biological processes. Cirrhosis is a syndrome in which chronic liver diseases converge, leading to hepatocellular injury, the exacerbated deposition of fibrous tissue, and eventually the disruption of the tissue architecture. The liver is subject to potential injury by a large quantity of pharmacological Biotemas, 23 (2): 183-190, junho de 2010

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Oxidative stress in the development of liver cirrhosis: A comparison of two different experimental models

Abstract: These results suggest that evidence of oxygen free radicals is also found early in the development of fibrosis and cirrhosis in both models.

Cited by 107 publications

References 48 publications

Renal damage in experimentally-induced cirrhosis in rats: Role of oxygen free radicals

Renal damage in experimentally-induced cirrhosis in rats: Role of oxygen free radicals

Stem Cell Therapy for Liver Disease: Parameters Governing the Success of Using Bone Marrow Mesenchymal Stem Cells

<b>Modelos experimentais para indução de cirrose hepática em animais: Revisão de literatura</b><br>doi: 10.5007/2175-7925.2010v23n2p183

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