OBJETIVO: Avaliar a função mitocondrial do fígado remanescente (FR) na fase precoce da regeneração hepática em ratos após hepatectomia parcial (HP) a 70%. MÉTODOS: Sessenta ratos machos Wistar (200 - 250g) submetidos à HP a 70%, foram distribuídos em cinco grupos de acordo com o tempo de eutanásia e com aplicação ou não de luz laser: C= Controle,tempo zero; 2 minutos, 4, 6 e 24 horas após HP. O laser foi utilizado na dose 22.5 J/cm², 660 nm, no FR.Estudou-se o estado 3 (respiração ativada por ADP), estado 4 (respiração mitocondrial basal), razão de controle respiratório,estado 3/estado 4 (RCR) e o potencial de membrana mitocondrial(PMM). RESULTADOS: A função mitocondrial do FR alterou-se no período de 4 e 6 horas após a HP com aumento significativo do estado 3 e aumento concomitante do estado 4, com manutenção da RCR. O PMM apresentou diferença significativa entre os grupos bioestimulados com laser e o controle a partir de 4 horas pós HP, com queda importante do grupo sem laser e tendência a equiparação dos valores após 24 horas. CONCLUSÃO: A luz laser, na dose utilizada no presente estudo, não induziu lesão adicional ao FR e parece ter retardado a sobrecarga hepatocelular do fígado remanescente.

PURPOSE: To evaluate the mitochondrial function of the remnant liver (RL) in the early phase of liver regeneration in rats after 70% partial hepatectomy (PH). METHODS: Sixty male Wistar rats (200-250g) submitted to 70% PH were divided into five groups according to the time of euthanasia and application or not of laser light: C = Control, time zero; 2 minutes, 4, 6 and 24 hours after PH. The dose of laser radiation was 22.5 J/cm², wavelength of 660 nm (visible/red), in the remnant liver. We studied the respiration activated by ADP (state 3), basal mitochondrial respiration (state 4), respiratory control ratio (RCR) and mitochondrial membrane potential (MMP). RESULTS: The mitochondrial function of RL changed at 4 and 6 hours after PH, with a significant increase in state 3 and a concomitant increase in state 4 and with maintenance of RCR. MMP differed significantly between the groups biostimulated with laser radiation and the control group 4 hours after HP, with a substantial reduction in the non-laser groups. CONCLUSION: The laser light at the dose used in this study did not induce additional damage to the RL and seems to have delayed the hepatocellular metabolic overload of the remnant liver.

OBJETIVO: Avaliar o efeito da luz laser em remanescentes hepáticos após hepatectomia a 90%. MÉTODOS: Aplicou-se luz laser com comprimento de onda de 660 nm e potência de 30 mw, por 30 segundos, na dose de 22,5 J/cm² em cada um deles, repetidos em cinco pontos do fígado remanescente, após realizada a hepatectomia a 90%. Os animais foram sacrificados para análise do fígado, contagem de hepatócitos em proliferação (Proliferating Cell Nuclear Antigen -PCNA), e coleta de sangue para dosagem serica das aminotransferases, após 24, 48 e 72 horas. RESULTADO: O índice de células marcadas teve significativo aumento no grupo de 72 horas irradiados com laser. CONCLUSÃO: A análise dos resultados demonstrou que o laser não causou lesões hepáticas adicionais à hepatectomia parcial e estimulou a atividade proliferativa hepatocelular.

PURPOSE: To evaluate the effect of laser beam on remanescent liver after partial hepatectomy 90%. METHODS: Wistar rats, (N= 42), were divided into six groups with seven specimens each. The partial hepatectomy (HP) was performed in all animals through exeresis of approximately 90% of the liver parenchyma. The animals from groups HP and Laser application, HPL24, HPL48 and HPL72 undertook laser irradiation carried out through application (dose of 22.5 J/cm²) in five different sites in the remanescent liver. The rats were then sacrificed 24, 48 and 72hours after HP procedure, for the liver regeneration analysis,using the Proliferating Cell Nuclear Antigen (PCNA),and for dosage of serum aminotransferases. RESULTS: Were demonstrated an increase of the serum levels of alanine aminotransferase for the group of 24 hours and a decrease for the group of 72 hours exposed to laser. The index of marked cells had a considerable more improvement for the group of 72 hours exposed in laser compared to other groups. CONCLUSION: Laser did not cause hepatic injuries additional to the partial hepatectomy and perhaps led to a benefit by stimulating the proliferative activity.

O objetivo desta revisão foi desenvolver uma análise do processo regenerativo do fígado, focando as interações moleculares envolvidas neste processo.Os processos celulares envolvidos na regeneração hepática requerem múltiplas ações sistemáticas relacionadas com citoquinas e fatores de crescimento. Estas interações resultam na iniciação do potencial mitogênico dos hepatócitos. A ação destes moduladores do processo regenerativo necessita de processamento no meio extra celular. As serinas e metaloproteínas são responsáveis pela biodisponibilização de citoquinas e fatores de crescimento, para que então possam interagir com receptores na membrana celular gerando os eventos sinalizadores para o inicio e o término do processo regenerativo hepático.O exato mecanismo de interação entre células, citoquinas e fatores de crescimento não está bem estabelecido. Tem-se descrito uma série de eventos ordenados que resulta na regeneração do tecido hepático. O melhor entendimento destas interações leva a uma nova abordagem de tratamento para doenças hepáticas, objetivando a indução do processo regenerativo.

The purpose of this review was to carry out an analysis of the liver regenerative process focusing on the molecular interactions involved in this process. The authors undertook a review of scientific publications with a focus on the liver regeneration.The cellular processes involved in liver regeneration require multiple systematic actions related to cytokines and growth factors. These interactions result in the initiation of mitogenic potential of the hepatocytes. The action of these modulators in the regenerative process require a processing in the extra-cellular matrix. Serines and metal proteins are responsible for the bio availability of cytokines and growth factors so that they can interact as receptors in the cellular membrane generating signaling events for the beginning and end of the liver regenerative process. The exact mechanism of interaction between cells, cytokines and growth factors is not well established yet. A series of ordered events that result in the hepatic tissue regeneration has been described. The better understanding of these interactions should provide a new approach of the treatment for liver diseases, aiming at inducing the regenerative process.

Este artigo tem como objetivo analisar aspectos da regeneração hepática (RH) sob a óptica celular. Em vigência de uma lesão neste órgão a capacidade regenerativa do hepatócito é suficientemente capaz de restabelecer o parênquima como um todo. Levando em conta a elevada capacidade regenerativa do hepatócito, a necessidade de um progenitor ou uma célula tronco hepática não era óbvia. Hoje esta bem estabelecido que células precursoras participam do processo regenerativo hepático. A célula tronco hepática, célula oval, atua como um precursor bipotencial, contribuindo para o restauro do fígado principalmente quando os hepatócitos se encontram impossibilitados de proliferar. Um outro precursor, a célula tronco de origem hematopoética (HSC), participa do processo regenerativo, originando células da linhagem hepatocítica e colangiócitos, assim como a células oval. Ainda não está estabelecido o meio como ocorre o fenômeno de transdiferenciação.Muitos estudos devem ser realizados no intuito de esclarecer questões, tais como a possível ocorrência de processo de fusão celular entre a HSC e as células hepáticas e a possibilidade de ser aplicado como uma nova terapêutica no tratamento de doenças associadas à insuficiência deste nobre órgão.

This paper has the objective to analyze the cellular aspects of liver regeneration (LR). Upon damage in this organ, the regenerative capacity of hepatocyte is sufficiently able to reestablish the parenchyma as a whole. Taking into account the regenerative capacity of hepatocyte, the need of a progenitor or a liver trunk cell was not obvious. Nowadays it is well-established that precursor cells take part in the liver regenerative process. The liver trunk cell, oval cell, acts as a bypotential precursor, contributing for the liver restoration, mainly when the hepatocytes are unable to proliferate. Another precursor, trunk cell of hematopoetic origin (HSC), takes part in the regenerative process, originating cells of the hepatocitic lineage and colangiocytes, as well as the oval cell. The way the trans-differentiation takes place is not established yet. A number of studies must be undertaken in order to clarify questions, such as the possible occurrence of cellular fusion process between the HSC and the hepatic cells and the possibility of application as a new therapeutic procedure in the treatment of diseases associated with insufficiency of this noble organ.

Recently, the LED (light emitting diode) developed by the Optics Group of IFSC-USP has been used instead of laser for the treatment of skin tumors by the PDT (Photodinamic Therapy) because of its low operational cost compared to the use of a laser. In this paper we investigate the effect of LED light on oxidative phosphorylation during liver regeneration after partial hepatectomy. Twenty-four male Wistar rats (250 g) were kept in identical housing units on a 12-hour light/12 hour dark cycle. The LED 10 group was exposed to LED at 638 nm (10 J/cm² for 3 minutes). Seventy percent partial hepatectomy was performed in the LED 10 and HPC (Partial Hepatectomy-Control). A sham-operated group (C) was used for control. Twenty four hours after the procedure, LED 10, HPC and control animals were sacrificed. Samples of liver tissue were used for the mitochondrial respiration assay. Statistical comparisons of the groups were performed by analysis of variance (ANOVA), followed by the Bonferroni post-test. Probability values less than 0.05 were considered to be statistically significant. the phosphorylation index (FI) for the LED 10 group was higher than that for the HPC group and for the sham group (p<005). The FI for the HPC group was higher than that for the sham group (p<005). The values of the ADP:O ratio for the three groups, which did not differ significantly from one another (p > 0.05). In the present study we noted an effective interaction between LED light and hepatic mitochondria, with an increased phosphorylation rate for the latter.