Hepatic Epigenetic Reprogramming After Liver Resection in Offspring Alleviates the Effects of Maternal Obesity.

Obesity has become a public health problem in recent decades, and during pregnancy, it can lead to an increased risk of gestational complications and permanent changes in the offspring resulting from a process known as metabolic programming. The offspring of obese dams are at increased risk of developing non-alcoholic fatty liver disease (NAFLD), even in the absence of high-fat diet consumption. NAFLD is a chronic fatty liver disease that can progress to extremely severe conditions that require surgical intervention with the removal of the injured tissue. Liver regeneration is necessary to preserve organ function. A range of pathways is activated in the liver regeneration process, including the Hippo, TGFß, and AMPK signaling pathways that are under epigenetic control. We investigated whether microRNA modulation in the liver of the offspring of obese dams would impact gene expression of Hippo, TGFß, and AMPK pathways and tissue regeneration after partial hepatectomy (PHx). Female Swiss mice fed a standard chow or a high-fat diet (HFD) before and during pregnancy and lactation were mated with male control mice. The offspring from control (CT-O) and obese (HF-O) dams weaned to standard chow diet until day 56 were submitted to PHx surgery. Prior to the surgery, HF-O presented alterations in miR-122, miR-370, and Let-7a expression in the liver compared to CT-O, as previously shown, as well as in its target genes involved in liver regeneration. However, after the PHx (4 h or 48 h post-surgery), differences in gene expression between CT-O and HF-O were suppressed, as well as in microRNA expression in the liver. Furthermore, both CT-O and HF-O presented a similar regenerative capacity of the liver within 48 h after PHx. Our results suggest that survival and regenerative mechanisms induced by the partial hepatectomy may overcome the epigenetic changes in the liver of offspring programmed by maternal obesity.

Maternal high-fat diet consumption programs male offspring to mitigate complications in liver regeneration.

In the last decades, obesity and nonalcoholic fatty liver disease (NAFLD) have become increasingly prevalent in wide world. Fatty liver can be detrimental to liver regeneration (LR) and offspring of obese dams (HFD-O) are susceptible to NAFLD development. Here we evaluated LR capacity in HFD-O after partial hepatectomy (PHx). HFD-O re-exposed or not to HFD in later life were evaluated for metabolic parameters, inflammation, proliferation, tissue repair markers and survival rate after PHx. Increasing adiposity and fatty liver were observed in HFD-O. Despite lower IL-6 levels, Ki67 labeling, cells in S phase and Ciclin D1/PCNA protein content, a lower impact on survival rate was found after PHx, even when re-exposed to HFD. However, no difference was observed between offspring of control dams (SC-O) and HFD-O after surgery. Although LR impairment is dependent of steatosis development, offspring of obese dams are programmed to be protected from the damage promoted by HFD.

Laparoscopic Hepatectomy via Remote Mentoring From Jamaica to Trinidad.

Laparoscopic hepatectomy brings many physiologic advantages over open hepatectomy and adheres to all oncologic principles. It is currently considered the standard of care. However, these are technically difficult operations to perform. Consequently, the expertise may not be universally available for all patients to benefit from laparoscopic hepatectomy. We report a unique situation where remote mentoring was used to guide bariatric surgeons in Jamaica to complete a laparoscopic hepatectomy.

MicroRNA-125a-3p overexpression promotes liver regeneration through targeting proline-rich acidic protein 1.

INTRODUCTION AND OBJECTIVES: Liver regeneration plays a valuable significance for hepatectomies, and is mainly attributed to hepatocyte proliferation. MicroRNA-125a-3p was reported to be highly associated with liver regeneration process. We studied the underlying mechanism of the functional role of miR-125a-3p in liver regeneration. MATERIALS AND METHODS: The miR-125a-3p mimics and inhibitor vector were constructed and transfected into primary human liver HL-7702 cells, the transfected cell viability was detected using cell counting kit-8 (CCK-8). Cell cycle distribution was analyzed by flow cytometry. With Targetscan and OUGene prediction, the potential targets of miR-125 were verified by real-time quantitative PCR (qPCR) and luciferase reporter assays in turn. The overexpression vector of proline-rich acidic protein 1 (PRAP1) was constructed and co-transfected with miR-125a-3p mimics into HL-7702 cells, detecting the changes of proliferative capacity and cell cycle distribution. Western blot and qPCR performed to analyze gene expressions. RESULTS: Overexpressed miR-125a-3p notably increased the hepatocyte viability at 48h, and decreased the number of G1 phase cells (p<0.05). However, miR-125a-3p inhibition suppressed the development of hepatocytes. PRAP1 was the target of miR-125a-3p. After co-transfection with PRAP1 vector, hepatocyte viability was decrease and the G1 phase cell number was increased (p<0.05). More importantly, overexpressed PRAP1 notably decreased the mRNA and protein levels of cyclin D1, cyclin-dependent kinase 2 (CDK2) and cell division cycle 25A (CDC25A). CONCLUSION: The elevated miR-125a-3p positively correlated with hepatocyte viability and cell cycle progression due to the modulation of PRAP1, and miR-125a-3p may contribute to improving liver regeneration.

Hepatoprotective Effect of Quercetin Pretreatment Against Paracetamol-Induced Liver Damage and Partial Hepatectomy in Rats

ABSTRACT Quercetin has potent antioxidant action and a hepatoprotective role. The aim of this study was to evaluate the hepatoprotective action of quercetin pretreatment in paracetamol-induced liver damage (PILD) and structural injury resulting from partial hepatectomy (PH). In the first model, Wistar rats received oral quercetin (50mg/kg/day) during 8 days. On the 8th day, 3g/kg paracetamol were added. In the second model, the same quercetin dose was given during 7 days and rats were submitted to PH on the 8th day. Blood samples were obtained for determination of enzyme levels. Liver, heart, kidney and lung tissue were also collected for assessment of quercetin biodistribution and/or histological analyses. The results obtained after PILD were more pronounced at 24 hours, as reflected by the reduction of serum ALT levels and by the lower concentration of quercetin in liver at this time point. Quercetin also had a protective effect in groups submitted to PH, as shown by decreased ALT levels after 18 hours, and of AST levels after 18 and 36h. The reduction in serum AST and ALT levels suggest that treatment with quercetin is useful as a preoperative pharmacologic measure and for prevention of liver damage caused by drugs.

Parenteral solution of nutritional hepatotrophic factors improves regeneration in thioacetamide-induced cirrhotic livers after partial hepatectomy.

Liver resection is a suitable option for the treatment of certain hepatic conditions, particularly hepatocarcinomas, in patients with cirrhosis. However, this disease impairs liver regeneration, which increases the risk of liver failure and postoperative death. Supportive treatments for regeneration of the remaining liver may be useful for the recovery of these patients. We demonstrated that nutritional hepatotrophic factors (NHF) is an effective regenerative stimulus for cirrhotic livers in rats subjected to partial hepatectomy (PH). The rats with thioacetamide-induced cirrhosis were subjected to PH, and they were divided into 2 groups. One group received intraperitoneal administration of NHF, and the other group received saline solution. After 12 days, biometric data, collagen content, hepatocyte regeneration (proliferation cell nuclear antigen immunochemistry), and profibrotic gene expression (Collagen-α1, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase 1, and transforming growth factor beta 1) were assessed. The results indicated that the rats treated with NHF after PH had an increased liver size, a reduced amount of collagen, and a higher hepatocyte proliferation index compared with the rats that underwent PH alone. In addition, collagen-α1 gene expression was decreased in the NHF-treated rats. Thus, postoperative improvement in the liver morphology following NHF treatment may cause a significant decrease in the risk of liver failure and mortality after hepatic resection.

Proteomic analysis of the regenerating liver following 2/3 partial hepatectomy in rats

BACKGROUND: Liver regeneration (LR) after 2/3 partial hepatectomy (PH) is one of the most studied models of cell, organ, and tissue regeneration. Although the transcriptional profile analysis of regenerating liver has been carried out by many reserachers, the dynamic protein expression profile during LR has been rarely reported up to date. Therefore, this study aims to detect the global proteomic profile of the regenerating rat liver following 2/3 hepatectomy, thereby gaining some insights into hepatic regeneration mechanism. RESULTS: Protein samples extracted from the sham-operated and the regenerating rat livers at 6, 12, 24, 72, 120 and 168 h after PH were separated by IEF/SDS-PAGE and then analyzed by MALDI-TOF/TOF mass spectrometry. Compared to sham-operated groups, there were totally 220 differentially expressed proteins (including 156 up-regulated, 62 down-regulated, and 2 up/down-regulated ones) identified in the regenerating rat livers, and most of them have not been previously related to liver regeneration. According to the expression pattern analysis combined with gene functional analysis, it showed that lipid and carbohydrate metabolism were enhanced at the early phase of LR and continue throughout the regeneration process. Ingenuity Pathway Analysis indicated that YWHAE protein (one of members of the 14-3-3 protein family) was located at the center of pathway networks at all the timepoints after 2/3 hepatectomy under our experimental conditions, maybe suggesting a central role of this protein in regulating liver regeneration. Additionally, we also revealed the role of Cdc42 (cell division cycle 42) in the termination of LR. CONCLUSIONS: For the first time, our proteomic analysis suggested an important role of YWHAE and pathway mediated by this protein in liver regeneration, which might be helpful in expanding our understanding of LR amd unraveling the mechanisms of LR.

Manejo anestésico en cirugía hepática, vía biliar y de páncreas

RESUMEN El paciente oncológico representa un reto intelectual y físico para el médico anestesiólogo. Dentro de la complejidad del tratamiento de cáncer, la cirugía hepática, de vía biliar y páncreas requieren consideraciones especiales. La epidemiología y el tipo de neoplasias específicas de esta zona del cuerpo hacen que los tratamientos quirúrgicos sean extensos y radicales para lograr ampliar la sobrevida de los pacientes. El manejo anestésico va encaminado a corregir y optimizar las comorbilidades del paciente previo a la cirugía. El transanestésico involucra un monitoreo invasivo para estabilizar hemodinámicamente al paciente y lograr mantener en adecuado plano anestésico a lo largo del procedimiento. La revisión que a continuación se expone es una actualización sobre la epidemiología y tipo de neoplasias que se involucran en esta zona. Se recuerdan los puntos importantes del manejo anestésico desde la valoración preoperatoria hasta el postoperatorio inmediato. Por último se sugiere un manejo anestésico óptimo basado en la literatura y en consensos de expertos en pacientes con estas condiciones.

SUMMARY Cancer patients are an intellectual and physical challenge for the anesthesiologist. Within the complexity of cancer treatment, surgery of liver, bile duct and pancreas requiere special attention. The specific types of neoplasmas in this area of the body along with their unique epidemiology, make surgical treatments to be radical with the objective of achieving a longer expectation of life. The anesthetic management is aimed to correct and optimize the patient´s comorbidities prior and during surgery. This involves invasive hemodynamic monitoring to keep the patient in an adequate level of anesthesia and stable in their neurologic, renal and cardiovascular variables. The review that is set out below is an update of the types of tumoral diseases that involve this area. Key points are being highlighted regarding the anesthetic management from the preoperative assessment until the inmmediate postoperative period.Finally we suggest an optimal anesthetic procedure based on literature and expert consensus in patients with these conditions.http://jaf.com.uy/2012/07/16/parador-al-aire-libre-en-pueblo-centenario/.

RESUMO O paciente oncológico apresenta um desafio intelectual e físico para o médico anestesiologista. Dentro da complexidade do tratamento, a cirurgia hepática, de via biliar, e pâncreas, requer considerações especiais. A epidemiologia, e o tipo de neoplasia especifica desta região do corpo, fazem com que os tratamentos cirúrgicos sejam extensos e radicais para conseguir uma maior sobrevida. O manejo anestésico visa a corrigir e diminuir as co-morbilidades do paciente previamente à cirurgia. O trans-anestésico obriga a um monitoramento invasivo para estabilizar hemodinamicamente o paciente e conseguir manter um adequado plano anestésico durante o procedimento. Nesta revisão continuada se expõe, uma atualizaçao da epidemiologia e o tipo de neoplasias que se envolvem nesta região. Recordam-se os pontos importantes do manejo anestésico desde a avaliação pré-operatório até o pós-operatório imediato. Por último se sugere um manejo anestésico ótimo fundamentado na literatura e no consenso de expertos em pacientes com estas condições.

Estratégias para aumentar a ressecabilidade em pacientes com metástases hepáticas de tumores colorretais / Strategies to increase resected liver metastases in patients with colorectal tumors

INTRODUÇÃO: Atualmente, as ressecções hepáticas podem ser realizadas com taxas aceitáveis de morbimortalidade. Em centros especializados, mortalidade ao redor de 1 por cento pode ser alcançada, mesmo em fígados previamente submetidos à quimioterapia por longo prazo. Com o objetivo de reduzir essas taxas, novas estratégias têm sido empregadas, como a embolização portal, ablação por radiofrequência, re-hepatectomias ressecções vasculares com reconstrução e hepatectomias em dois tempos. MÉTODO: Foi realizada revisão de literatura nos sites de pesquisa PubMed, Bireme e Scielo, com os descritores "hepatectomias parciais, metástases, neoplasia colorretal, radiofrequência e embolização". Selecionaram-se, principalmente, os estudos de aplicação de técnicas e procedimentos cirúrgicos no tratamento das metástases hepáticas. CONCLUSÃO: Sobrevida ao redor de 50 por cento em cinco anos podem ser conseguidas em casos selecionados quando equipe multidisciplinar está envolvida no tratamento. Com a melhora na técnica operatória, poupando-se parênquima hepático, e com o advento de novos agentes quimioterápicos, lesões metastáticas hepáticas irressecáveis podem se tornar ressecáveis e a sobrevida a longo prazo pode ser alcançada.

INTRODUCTION: Nowadays, liver resections can be performed with acceptable morbi-mortality rates. In specialized centers, mortality as low as 1 percent can be achieved, even with the advent of new hepatotoxic chemotherapy regimens. In order to reduce morbidity and mortality, newer strategies can be undertaken, such as portal vein embolization, radiofrequency ablation techniques, re-hepatectomies, major vascular resections and two stages hepatectomies. METHOD: Literature review was conducted on sites search PubMed, BIREME, SciELO, with the headings "partial hepatectomy, hepatic metastases, colorectal cancer, radiofrequency and embolization". Were selected mainly studies with the application of techniques and surgical procedures in the treatment of liver metastasis. CONCLUSION: Survival rates as good as 50 percent in 5y can be achieved in selected cases when a multidisciplinary team is involved. Better surgical techniques, with parenchimal sparing strategies and the advent of neoadjuvant chemotherapy can turn unresectable liver lesions to resectable and increase survival rates.

Alterations in DNA repair gene expression and their possible regulation in rat-liver regeneration.

Rapidly proliferating tissue may require enhanced DNA repair capacity in order to avoid fixation of promutagenic DNA lesions to mutations. Partial hepatectomy (PH) triggers cell proliferation during liver regeneration (LR). However, little is known on how DNA repair genes change and how they are regulated at the transcriptional level during LR. In the present study, the Rat Genome 230 2.0 array was used to detect the expression profiles of DNA repair genes during LR, and differential expression of selected genes was confirmed by real-time RT-PCR. 69 DNA repair genes were found to be associated with LR, more than half of which distributed in a cluster characterized by a gradual increase at 24-72h and then returning to normal. The expression of base excision repair- and transcription-coupled repair-related genes was enhanced in the early and intermediate phases of LR, whereas the expression of genes related to HR, NHEJ and DNA cross-link repair, as well as DNA polymerases and related accessory factors, and editing or processing nucleases, were mainly enhanced in the intermediate phase. The expression changes of genes in DNA damage response were complicated throughout the whole LR. Our data also suggest that the expression of most DNA repair genes may be regulated by the cell cycle during LR.

Alterations in DNA repair gene expression and their possible regulation in rat-liver regeneration

Rapidly proliferating tissue may require enhanced DNA repair capacity in order to avoid fixation of promutagenic DNA lesions to mutations. Partial hepatectomy (PH) triggers cell proliferation during liver regeneration (LR). However, little is known on how DNA repair genes change and how they are regulated at the transcriptional level during LR. In the present study, the Rat Genome 230 2.0 array was used to detect the expression profiles of DNA repair genes during LR, and differential expression of selected genes was confirmed by real-time RT-PCR. 69 DNA repair genes were found to be associated with LR, more than half of which distributed in a cluster characterized by a gradual increase at 24-72h and then returning to normal. The expression of base excision repair- and transcription-coupled repair-related genes was enhanced in the early and intermediate phases of LR, whereas the expression of genes related to HR, NHEJ and DNA cross-link repair, as well as DNA polymerases and related accessory factors, and editing or processing nucleases, were mainly enhanced in the intermediate phase. The expression changes of genes in DNA damage response were complicated throughout the whole LR. Our data also suggest that the expression of most DNA repair genes may be regulated by the cell cycle during LR.

The effect of laser on remanescent liver tissue after 90 percent hepatectomy in rats / Efeito do laser no tecido hepático após hepatectomia a 90 por cento em ratos

PURPOSE: To evaluate the effect of laser beam on remanescent liver after partial hepatectomy 90 percent. 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 percent 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.

OBJETIVO: Avaliar o efeito da luz laser em remanescentes hepáticos após hepatectomia a 90 por cento. 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 por cento. 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.

Proliferative effect of the aqueous extract of Hyptis pectinata on liver regeneration after partial hepatectomy in rats / Efeito do extrato aquoso da Hyptis pectinata na regeneração hepática após hepatectomia parcial em ratos

PURPOSE: This study was carried out to assess the effects of the aqueous extract of Hyptis pectinata leaves on liver regeneration and on serum enzymes (AST, ALT and gamma-GT) after 67 percent partial hepatectomy in rats. METHODS: AST, ALT and gamma-GT, were determined by conventional procedures using a spectrophotometer (Model E2250-CELM). Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). RESULTS:Oral pretreatment during 4 days at 100 mg/kg increased liver regeneration index. At 200 mg/kg, AST level was statistically decreased in comparison to the group submited to distilled water administration. The other enzymes assessed disclosed no difference when all groups were compared. CONCLUSION: The present study shows that the aqueous extract of Hyptis pectinata leaves contains some biological active principles that stimulate liver regeneration at 100 mg/kg and cause slight hepatic protection at 200 mg/kg.

OBJETIVO: Este estudo foi realizado com o objetivo de verificar o efeito do extrato aquoso da Hyptis pectinata na regeneração hepática bem como nos níveis das enzimas séricas (AST, ALT e gama-GT) após hepatectomia parcial de 67 por cento em ratos. MÉTODOS: AST, ALT e gama-GT, foram determinadas pelo método cinético utilizando um espectrofotômetro (Modelo E2250-CELM). A regeneração hepática foi avaliada por imunohistoquímica (PCNA). RESULTADOS: O pré-tratamento oral de 100 mg/kg foi realizado durante 4 dias e causou aumento na regeneração hepática O pré-tratamento oral com 200 mg/kg diminuiu significativamente os níveis de AST quando comparado com o grupo submetido ao pré-tratamento com água destilada. As demais enzimas avaliadas não apresentaram diferenças quando comparadas entre os grupos estudados. CONCLUSÃO: O presente estudo mostra que o extrato aquoso da Hyptis pectinata, numa concentração de 100 mg/kg possui alguma atividade biológica estimulando a regeneração hepática e causando também um leve efeito hepatoprotetor numa concentração de 200 mg/kg.

Effect of the aqueous extract of Sida cordifolia on liver regeneration after partial hepatectomy / Efeito do extrato aquoso de Sida cordifolia na regeneração hepática após hepatectomia parcial

PURPOSE: The use of medicinal plants for the treatment of human diseases has increased worldwide. Many of them are used by oral administration and, after absorption, may affect many organs. Therefore, this study aimed at assessing the effects of the aqueous extract of Sida cordifolia leaves, popularly known in Brazil as "malva-branca", on liver regeneration. METHODS: Twenty rats were divided into four groups: control, Sida100, Sida200 and Sida400 groups. All animals were submitted to oral administration of distilled water, 100, 200 and 400 mg/kg of the aqueous extract of Sida cordifolia, respectively. Immediately after this, they underwent 67 percent partial hepatectomy. Twenty four hours later, their livers were removed. Hepatic regeneration was assessed by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using the PC-10 monoclonal antibody. RESULTS: Sida100 and Sida200 groups disclosed higher liver regeneration indices than control group (p<0.001 and p<0.05, respectively). CONCLUSION: The aqueous extract of Sida cordifolia stimulates liver regeneration after 67 percent partial hepatectomy in rats.

INTRODUÇÃO: O uso de plantas medicinais para o tratamento de patologias humanas tem aumentado em todo mundo. Muitas delas são usadas por administração oral, e após a absorção podem afetar muitos órgãos. OBJETIVO: Esse estudo, tem como objetivo verificar o efeito do extrato aquoso de Sida cordifolia, popularmente conhecida no Brasil como "malva-branca", na regeneração hepática. MÉTODOS: Vinte ratos foram divididos em 4 grupos: controle, Sida 100, Sida 200 e Sida 400. Os animais foram submetidos a administração oral de água destilada, 100, 200 e 400 mg/kg de extrato aquoso de Sida cordifolia, respectivamente. Imediatamente após, foi realizada hepatectomia parcial 67 por cento. Vinte quatro horas após, os fígados foram removidos. A regeneração hepática foi avaliada por imunohistoquímica (PCNA), usando o anticorpo monoclonal PC-10. RESULTADOS: Os grupos Sida100 e Sida200 mostraram índices de regeneração hepática maiores que o grupo controle (p<0.001 e p<0.05, respectivamente). CONCLUSÃO: O extrato aquoso de Sida cordifolia estimula a regeneração hepática após hepatectomia parcial a 67 por cento em ratos.

Effect of the aqueous extract of Sida cordifolia on liver regeneration after partial hepatectomy / Efeito do extrato aquoso de Sida cordifolia na regeneração hepática após hepatectomia parcial

PURPOSE: The use of medicinal plants for the treatment of human diseases has increased worldwide. Many of them are used by oral administration and, after absorption, may affect many organs. Therefore, this study aimed at assessing the effects of the aqueous extract of Sida cordifolia leaves, popularly known in Brazil as "malva-branca", on liver regeneration. METHODS: Twenty rats were divided into four groups: control, Sida100, Sida200 and Sida400 groups. All animals were submitted to oral administration of distilled water, 100, 200 and 400 mg/kg of the aqueous extract of Sida cordifolia, respectively. Immediately after this, they underwent 67 percent partial hepatectomy. Twenty four hours later, their livers were removed. Hepatic regeneration was assessed by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using the PC-10 monoclonal antibody. RESULTS: Sida100 and Sida200 groups disclosed higher liver regeneration indices than control group (p<0.001 and p<0.05, respectively). CONCLUSION: The aqueous extract of Sida cordifolia stimulates liver regeneration after 67 percent partial hepatectomy in rats.(AU)

INTRODUÇÃO: O uso de plantas medicinais para o tratamento de patologias humanas tem aumentado em todo mundo. Muitas delas são usadas por administração oral, e após a absorção podem afetar muitos órgãos. OBJETIVO: Esse estudo, tem como objetivo verificar o efeito do extrato aquoso de Sida cordifolia, popularmente conhecida no Brasil como "malva-branca", na regeneração hepática. MÉTODOS: Vinte ratos foram divididos em 4 grupos: controle, Sida 100, Sida 200 e Sida 400. Os animais foram submetidos a administração oral de água destilada, 100, 200 e 400 mg/kg de extrato aquoso de Sida cordifolia, respectivamente. Imediatamente após, foi realizada hepatectomia parcial 67 por cento. Vinte quatro horas após, os fígados foram removidos. A regeneração hepática foi avaliada por imunohistoquímica (PCNA), usando o anticorpo monoclonal PC-10. RESULTADOS: Os grupos Sida100 e Sida200 mostraram índices de regeneração hepática maiores que o grupo controle (p<0.001 e p<0.05, respectivamente). CONCLUSÃO: O extrato aquoso de Sida cordifolia estimula a regeneração hepática após hepatectomia parcial a 67 por cento em ratos.(AU)

Proliferative effect of the aqueous extract of Hyptis pectinata on liver regeneration after partial hepatectomy in rats / Efeito do extrato aquoso da Hyptis pectinata na regeneração hepática após hepatectomia parcial em ratos

PURPOSE: This study was carried out to assess the effects of the aqueous extract of Hyptis pectinata leaves on liver regeneration and on serum enzymes (AST, ALT and gamma-GT) after 67 percent partial hepatectomy in rats. METHODS: AST, ALT and gamma-GT, were determined by conventional procedures using a spectrophotometer (Model E2250-CELM). Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). RESULTS:Oral pretreatment during 4 days at 100 mg/kg increased liver regeneration index. At 200 mg/kg, AST level was statistically decreased in comparison to the group submited to distilled water administration. The other enzymes assessed disclosed no difference when all groups were compared. CONCLUSION: The present study shows that the aqueous extract of Hyptis pectinata leaves contains some biological active principles that stimulate liver regeneration at 100 mg/kg and cause slight hepatic protection at 200 mg/kg.(AU)

OBJETIVO: Este estudo foi realizado com o objetivo de verificar o efeito do extrato aquoso da Hyptis pectinata na regeneração hepática bem como nos níveis das enzimas séricas (AST, ALT e gama-GT) após hepatectomia parcial de 67 por cento em ratos. MÉTODOS: AST, ALT e gama-GT, foram determinadas pelo método cinético utilizando um espectrofotômetro (Modelo E2250-CELM). A regeneração hepática foi avaliada por imunohistoquímica (PCNA). RESULTADOS: O pré-tratamento oral de 100 mg/kg foi realizado durante 4 dias e causou aumento na regeneração hepática O pré-tratamento oral com 200 mg/kg diminuiu significativamente os níveis de AST quando comparado com o grupo submetido ao pré-tratamento com água destilada. As demais enzimas avaliadas não apresentaram diferenças quando comparadas entre os grupos estudados. CONCLUSÃO: O presente estudo mostra que o extrato aquoso da Hyptis pectinata, numa concentração de 100 mg/kg possui alguma atividade biológica estimulando a regeneração hepática e causando também um leve efeito hepatoprotetor numa concentração de 200 mg/kg.(AU)

The effect of laser on remanescent liver tissue after 90 percent hepatectomy in rats / Efeito do laser no tecido hepático após hepatectomia a 90 por cento em ratos

PURPOSE: To evaluate the effect of laser beam on remanescent liver after partial hepatectomy 90 percent. 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 percent 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.(AU)

OBJETIVO: Avaliar o efeito da luz laser em remanescentes hepáticos após hepatectomia a 90 por cento. 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 por cento. 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.(AU)

Efeito do omeprazol e do pantoprazol sobre a regeneração hepática após hepatectomia parcial em ratos

PURPOSE: To assess the effects of omeprazole and pantoprazole on liver regeneration after partial hepatectomy. METHODS: Fifty eight male Wistar rats were divided into 4 groups: SHAM, HP, PANTO and OMEP Groups. They were submitted to 67% partial hepatectomy (HP, PANTO and OMEP Groups) or laparotomy (SHAM Group). Their livers were removed 32 and 56 hours after the operation. Then, the animals were sacrificed. In all groups, the substances (saline solution, omeprazole and pantoprazole) were injected once daily from the moment they were operated on until the time of sacrifice. RESULTS: In SHAM Group the mitotic index was not significant. Thirty two hours after hepatectomy, the mitosis index was 1.2 ± 1.09 in HP Group, 1.2 ± 1.6 in OMEP Group and 2.6 ± 3.2 in PANTO Group. Concerning the 56-hour analysis, the values were 1.6 ± 0.89 in HP Group, 2 ± 1.8 in OMEP Group and 2.6 ± 0.54 in PANTO Group. These results were not statistically significant. CONCLUSION: Omeprazole and pantoprazole, proton pump inhibitors (H+, K+-ATPase), do not cause any change on liver regeneration 32 and 56 hours after 67% partial hepatectomy in rats.

OBJETIVO: Avaliar os efeitos do omeprazol e do pantoprazol sobre a regeneração hepática após hepatectomia parcial. MÉTODOS: Cinqüenta e oito ratos Wistar machos foram divididos em 4 grupos: Grupo SHAM, Grupo HP, Grupo PANTO e Grupo OMEP. Eles foram submetidos a hepatectomia parcial de 67% (Grupos HP, PANTO e OMEP) ou laparotomia (Grupo SHAM). Os fígados foram removidos 32 e 56 horas após a operação. Depois, os animais foram sacrificados. Em todos os grupos, as substâncias (solução salina, omeprazol e pantoprazol) foram aplicadas diariamente a partir do momento em que foram operados até o sacrifício. RESULTADOS: O índice de mitose no Grupo SHAM não foi significativo. Trinta e duas horas após a hepatectomia, a contagem de mitoses foi de 1,2 ± 1,09 para o Grupo HP, 1,2 ± 1,6 para o Grupo OMEP e 2,6 ± 3,2 para o Grupo PANTO. Na análise após 56 horas, os valores foram 1,6 ± 0,89 para o HP, 2 ± 1,8 para o OMEP e 2,6 ± 0,54 para o PANTO. Esses resultados não foram estatisticamente significativos. CONCLUSÃO: O omeprazol e o pantoprazol, agentes inibidores da bomba de prótons (H+, K+-ATPase), não interferem na regeneração hepática 32 e 56 horas após hepatectomia parcial a 67% em ratos.

Modelo experimental de hepatectomia parcial laparoscópica em ratos

PURPOSE: To describe a model of laparoscopic partial hepatectomy in rats. METHODS: 35 male rats Rattus Norvegicus albinus Wistar weighing 250 +/- 50 g were used in this study. The animals were anaesthetised with ketamin and xilasin and insufflated with PCO2 of 7 mmHg through a Veress needle. After the pneumoperitoneum, two 5 mm and a 11 mm trocars were passed through the abdominal wall, so as to form a triangular geometrical figure. The ligature of three hepatic lobes (left, median left and median right) was done with Endoloop and the electrocoagulation of hemorrhagic spots with the hook. The animals were sacrificed after an eight-day observation period. RESULTS: Three animals (8,6%) died at the anaesthetic induction. After an eight-day observation period, 30 animals survived (85,7%) and only 2 (5,7%) died immediately after the surgery. In relation to complications, granuloma was observed in 54,3% (n=19). No conversion to open surgery was necessary. CONCLUSION: The model of laparoscopic partial hepatectomy in rats using surgical material similar to that used in humans is doable for surgeons' training and improvement.

OBJETIVO: Descrever um modelo experimental de hepatectomia parcial laparoscópica em ratos. MÉTODOS: Foram utilizados 35 ratos Rattus Norvegicus albinus da linhagem Wistar todos machos pesando 250+/-50g. Os animais foram anestesiados com cetamina e xilasina, e submetidos à insuflação através da agulha de Veress com PCO2 de 7mmHg. Após o pneumoperitôneo foram transpassados pela parede abdominal dois trocateres com 5 e um com 11 mm de espessura, de tal modo a formarem uma figura geométrica triangular. A ligadura de três lobos hepáticos (esquerdo, central esquerdo e central direito) foi feita utilizando-se o "endoloop" e a eletrocoagulação dos pontos hemorrágicos através do "hook". Os animais foram sacrificados após um período de observação de oito dias. RESULTADOS: Três animais (8,6%) morreram na indução anestésica. Após um período de observação de oito dias 30 animais sobreviveram (85,7%), e apenas 2 (5,7%) vieram a óbito no pós-operatório imediato. Quanto às complicações, a presença de granuloma foi observada em 54,3% dos ratos (n=19). Nenhuma conversão para a cirurgia aberta foi necessária. CONCLUSÃO: O modelo de hepatectomia parcial laparoscópica em ratos utilizando material cirúrgico semelhante ao usado em humanos é factível para o treinamento e aprimoramento de novos cirurgiões.

Alterações bioquímicas e morfológicas após anastomose porto-cava e hepatectomia parcial: estudo experimental em cães

PURPOSE: The aim of this study was to assess the effect of portocaval shunt on liver biochemical and morphological aspects in dogs. METHODS: Twenty animals were divided into 2 groups: Group I was submitted to 28.7% partial hepatectomy and Group II underwent partial hepatectomy associated with portocaval shunt. The data analyzed were: body weight, serum cholesterol and triglyceride, hepatic lipids and glycogen and liver regeneration index. All these data were measured preoperatively and 30 days after surgery. RESULTS: In Group I, only hepatic lipids levels were statistically increased post-operatively. In Group II, serum cholesterol and hepatic glycogen values were reduced while hepatic lipids levels were increased 30 days after surgery. When both groups were compared to each other, serum cholesterol, hepatic glycogen and liver regeneration index showed statistically significant difference. CONCLUSION: Portocaval shunt causes morphological and biochemical impairment of the liver as well as reduction of body weight.

OBJETIVO: Estudar os efeitos da anastomose porto-cava sobre a morfologia e bioquímica do fígado de cães. MÉTODOS: Vinte animais foram divididos em 2 grupos: o Grupo I foi submetido à hepatectomia parcial de 28,7% e o Grupo II, à hepatectomia parcial associada à derivação porto-cava. Os parâmetros analisados foram: peso corpóreo, colesterol e triglicérides plasmáticos, lipídios e glicogênio hepáticos e índice ponderal de regeneração hepática. Os dados foram analisados no pré-operatório e no 30° dia do pós-operatório. RESULTADOS: No Grupo I, apenas os lipídios hepáticos estavam significativamente elevados 30 dias após a cirurgia. No Grupo II, o colesterol plasmático e o glicogênio hepático apresentaram redução no pós-operatório, enquanto os lipídios hepáticos estavam significativamente elevados. Comparando-se os 2 grupos, houve diferença estatisticamente significativa nos valores do colesterol plasmático, do glicogênio e do índice de regeneraçãohepática. CONCLUSÃO: A anastomose porto-cava causa prejuízos morfológicos e bioquímicos significativos ao fígado, além de redução significativa do peso corpóreo.