Liver Regeneration in Surgical Animal Models – A Historical Perspective and Clinical Implications

Mortensen, Kim Erlend; Revhaug, Arthur

doi:10.1159/000321361

Cited by 35 publications

(46 citation statements)

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“…In experimental partial hepatectomy (PH) in pigs and rats, 75 removal of two thirds of the liver mass caused an effective increase in hepatic portal 76 blood flow (Kahn et al, 1984;Rice et al, 1977). It is unclear whether liver 77 regeneration is stimulated by the increase in blood flow or by increased delivery of 78 hepatotrophic substances in the portal blood (Mortensen and Revhaug, 2011). This 79 increase in portal blood flow relative to liver mass is similar to that observed 80 following CPSS attenuation.…”

mentioning

confidence: 84%

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Tivers

Lipscomb

Smith

et al. 2015

The Veterinary Journal

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Plasma LPS concentrations were measured in the peripheral and portal blood 37 using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly 38 greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 39 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) 40and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those 41 for control dogs. The relative mRNA expression of cytokines and TLRs was 42 measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 43 expression significantly increased following partial CPSS attenuation (P = 0.020). 44 TLR4 expression was significantly greater in dogs that tolerated complete CPSS 45 attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 46 0.004) and post-attenuation (P = 0.015) portovenography. Serum IL-6 concentration 47 was measured using a canine specific ELISA and significantly increased 24 h 48 following CPSS attenuation (P < 0.001). 49Portal LPS was increased in dogs with CPSS, consistent with decreased 50 hepatic clearance. TLR4 mRNA expression was significantly associated with portal 51 blood flow and increased following surgery. These findings support the concept that 52 portal LPS delivery is important in the hepatic response to surgical attenuation. Serum 53 IL-6 significantly increases following surgery, consistent with LPS stimulation via 54 TLR4, although this increase might be non-specific. 55 3

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confidence: 84%

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Tivers

Lipscomb

Smith

et al. 2015

The Veterinary Journal

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“…8,9,10 Na verdade, essas propriedades são as bases fundamentais da cirurgia hepática, ou seja, das ressecções hepáticas parciais e do transplante de fígado, que, ao crescer após um desafio, mantém sua vitalidade funcional e metabólica. Entretanto, nossos projetos de pesquisa têm procurado agentes que possam estimular o fígado a regenerar-se a limites além daqueles que ele naturalmente consegue, visando ampliar os limites da indicação do tratamento e melhorar os resultados terapêuticos.…”

Section: Professor Titular Da Universidade De São Paulo E Chefe Dounclassified

“…A fotobioestimulação baseia-se no nível mais sutil de interação da luz com tecidos, em que o fóton transmite sua energia a um composto fotossensível. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Pressupõe-se que a luz laser conduza a alterações conformacionais na estrutura dos citocromos dos hepatócitos, de modo que haveria um incremento na produção de ATP, expressando um aumento no metabolismo energético de fí-gado de ratos hepatectomizados. 16,20 Foi demonstrado que a luz laser, tanto de alta quanto baixa potência, tem a capacidade de elevar o índice mitótico e função mitocondrial no remanescente hepático após ressecções parciais em ratos não cirróticos.…”

Section: Professor Titular Da Universidade De São Paulo E Chefe Dounclassified

“…A perda tecidual rapidamente desencadeia o processo regenerativo até que o peso original seja recuperado. A constatação da resposta do fígado aos vários desafios, como as hepatites, as intoxicações, as ressecções hepáticas e o transplante de fíga-do, é mitológica [8][9][10][11][12] e levanta aspectos extremamente interessantes sobre a coerência do fígado em superar desafios e vencer obstáculos. Hesíodo relatou, em sua Teogônia, escrita no século VIII a.C., que Prometeu roubou o fogo escondido no Olimpo para entregá-lo aos homens.…”

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Fígado e luz. Uma combinação precisa, da mitologia à medicina

Silva

Silveira²

2013

Medicina (Ribeirão Preto)

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Hesíodo relatou, em sua Teogônia, escrita no século VIII a.C., que Prometeu roubou o fogo escondido no Olimpo para entregá-lo aos homens. Para castigá-lo, Zeus enviou-lhe a bela Pandora, portadora de uma caixa que, ao ser aberta, espalharia todos os males sobre a Terra. Como Prometeu resistiu aos encantos dessa mensageira, Zeus ordenou que Vulcano o acorrentasse a um rochedo no cimo do monte Cáucaso, onde todos os dias uma águia (ou abutre) ia comer-lhe o fígado, que regenerava durante a noite, mantendo constante a fonte de alimento da ave, e Prometeu sob tortura perpétua.13 Teria a luz do luar, propriedades indutórias sobre a regeneração hepática, diferentes das do sol ? Talvez haja uma mensagem, implícita, neste sentido.Apesar de Prometeu ser um titã, e dessa forma, imortal, o processo regenerativo do fígado, descrito nessa passagem da mitologia Grega, é a mais famosa e citada referência histórica nos trabalhos que se remetem ao processo de regeneração hepática na literatura médica. Na literatura brasileira, Castro Alves, na sua famosa Vozes D'Africa, de 1868, compara de forma poética o sofrimento eterno de Prometeu ao do território africano, deixando nas entrelinhas o poder de regeneração do fígado na manutenção da vida de Prometeu.Estudos recentes, utilizando-se de hepatectomias parciais sequenciais, mostraram que o fíga-do é capaz de se regenerar completamente depois de

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“…Photobiostimulation is based on the most subtle level of light interaction with tissues, with the photon transmitting its energy to a photosensitive compound. Laser light in the visible range of the spectrum is assumed to lead to conformational changes in the cytochrome structure of hepatocytes, thus inducing increased ATP production that expresses an increase in the energy metabolism of the liver of hepatectomized rats [11][12][13] . It has been demonstrated that both high and low power laser light has the ability to increase the mitotic index and mitochondrial function of the liver remnant after partial resection in non-cirrhotic rats 5 .…”

Section: Introductionmentioning

confidence: 99%

Effect of irradiation with different laser wavelengths on oxidative stress of non-hepatectomized rats

et al. 2016

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Paulo (FMRP-USP), Ribeirão Preto-SP, Brazil. Designed the protocol, responsible for manuscript preparation, manuscript writing, responsible for intellectual and scientific content of the study and english language.ABSTRACT PURPOSE:To assess the effect of two laser wavelengths, either separate or combined, on intact rat livers.METHOD:Nineteen male Wistar rats (200-300 g) were submitted to laser irradiation at 5 different sites on the liver surface.Wavelengths 660 and 780 nm were used, with a dose of irradiation of 60 J/cm 2 /site.The animals were divided into the groups:control (C) and animals irradiated with 660 nm laser (L1), with 780 nm laser (L2) or withboth wavelengths (L3).Mitochondrial function, mitochondrial swelling, and hepatocellular malondialdehyde (MDA) levels were determined.Data were analyzed by the Mann-Whitney test, with the level of significance set at 5%. RESULTS:There was a reduction of ADP-activated respiration (state 3) in group L1 compared to group C (p=0.0016), whereas the values of group L2 were similar to control.Group L3 also showed a reduction of state 3 (p=0.0159).There was a reduction of RCR in group L1 compared to control (p=0.0001) and to group L2 (p=0.0040).Mitochondrial swelling only differed between group L3 and control (p=0.0286).There was a increase in MDA levels in group L3 compared to control (p=0.0476) and to group L2 (p=0.0286) and in group L1 compared to group L2 (p=0.0132).CONCLUSION:Although laser irradiation reduced mitochondrial function,it did not interfere with the hepatocellular energy status.

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Liver Regeneration in Surgical Animal Models – A Historical Perspective and Clinical Implications

Cited by 35 publications

References 233 publications

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Fígado e luz. Uma combinação precisa, da mitologia à medicina

Effect of irradiation with different laser wavelengths on oxidative stress of non-hepatectomized rats

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