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      TRANEXAMIC ACID ACTION ON LIVER REGENERATION AFTER PARTIAL HEPATECTOMY: EXPERIMENTAL MODEL IN RATS Translated title: Ação do ácido tranexâmico na regeneração hepática após hepatectomia parcial: modelo experimental em ratos

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          ABSTRACT

          Background:

          Different lesions may affect the liver resulting in harmful stimuli. Some therapeutic procedures to treat those injuries depend on liver regeneration to increase functional capacity of this organ.

          Aim:

          Evaluate the effects of tranexamic acid on liver regeneration after partial hepatectomy in rats.

          Method:

          40 rats ( Rattus norvegicus albinus, Rodentia mammalia) of Wistar-UP lineage were randomly divided into two groups named control (CT) and tranexamic acid (ATX), with 20 rats in each. Both groups were subdivided, according to liver regeneration time of 32 h or seven days after the rats had been operated. The organ regeneration was evaluated through weight and histology, stained with HE and PCNA.

          Results:

          The average animal weight of ATX and CT 7 days groups before surgery were 411.2 g and 432.7 g, and 371.3 g and 392.9 g after the regeneration time, respectively. The average number of mitotic cells stained with HE for the ATX and CT 7 days groups were 33.7 and 32.6 mitosis, and 14.5 and 14.9 for the ATX and CT 32 h groups, respectively. When stained with proliferating cell nuclear antigen, the numbers of mitotic cells counted were 849.7 for the ATX 7 days, 301.8 for the CT 7 days groups, 814.2 for the ATX 32 hand 848.1 for the CT 32 h groups.

          Conclusion:

          Tranexamic acid was effective in liver regeneration, but in longer period after partial hepatectomy.

          RESUMO

          Racional:

          Muitas são as injúrias que acometem o fígado e levam a estímulo lesivo. Alguns procedimentos terapêuticos para tratamento dessas lesões dependem da regeneração hepática para aumentar a sua capacidade funcional.

          Objetivo:

          Avaliar o efeito do ácido tranexâmico na regeneração hepática após hepatectomia parcial em ratos.

          Método:

          Foram utilizados 40 ratos ( Rattus norvegicus albinus, Rodentia mammalia) convencionais da linhagem Wistar-UP. Foram divididos aleatoriamente em dois grupos de 20: grupo controle (CT) e grupo ácido tranexâmico (ATX). Cada um deles foi divido em dois subgrupos para avaliar a regeneração hepática no tempo de 32 h e 7 dias do pós-operatório. A regeneração do órgão foi avaliada quanto ao peso e histologia, sendo esta última por hematoxilina-eosina e antígeno nuclear de proliferação celular.

          Resultados:

          A média dos pesos dos animais dos grupos ATX 7 dias e CT 7 dias no pré-operatório foram de 411,2 g e 432,7 g, respectivamente, e após a regeneração foram de 371,3 g e 392,9 g. As médias das taxas de mitose coradas por HE dos dois grupos em 7 dias foram de 33,7 e 32,6 mitoses, respectivamente, e de 14,5 e 14,9 mitoses para os grupos ATX e CT 32 h. A contagem de células por antígeno nuclear de proliferação celular mostrou valores de 849,7 para o grupo ATX 7 dias e 301,8 para o CT 7 dias; 814,2 para o grupo ATX 32 h e 848,1 para o CT 32 h.

          Conclusão:

          O ácido tranexâmico mostrou-se efetivo na regeneração hepática somente em período mais longo de observação após hepatectomia parcial.

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          Most cited references46

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          Liver regeneration.

          Liver regeneration after the loss of hepatic tissue is a fundamental parameter of liver response to injury. Recognized as a phenomenon from mythological times, it is now defined as an orchestrated response induced by specific external stimuli and involving sequential changes in gene expression, growth factor production, and morphologic structure. Many growth factors and cytokines, most notably hepatocyte growth factor, epidermal growth factor, transforming growth factor-alpha, interleukin-6, tumor necrosis factor-alpha, insulin, and norepinephrine, appear to play important roles in this process. This review attempts to integrate the findings of the last three decades and looks toward clues as to the nature of the causes that trigger this fascinating organ and cellular response.
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            Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration.

            An enzyme-linked immunosorbent assay was used to measure the level of hepatocyte growth factor in rat plasma at various times after two-thirds partial hepatectomy or CCl4 administration. An initial 17-fold rise and 13-fold rise in the level of hepatocyte growth factor was observed 2 hr after partial hepatectomy and CCl4 treatment, respectively, well before the onset of DNA synthesis in the liver. The peaks of DNA synthesis in remnant livers and livers exposed to CCl4 occurred at 24 hr and 48 hr, respectively, as determined by 5-bromo-2'-deoxyuridine labeling and [3H]thymidine uptake by the liver. A later peak level (17-fold above control) of hepatocyte growth factor at 24 hr after CCl4 treatment coincided with strong immunostaining of damaged or necrotic hepatocytes around central veins with an antibody to hepatocyte growth factor. This suggests a later intrahepatic origin of the signals for liver regeneration after hepatotoxic injury subsequent to the early extrahepatic production of hepatocyte growth factor at 2 hr after CCl4 administration. The absence of staining in the liver remnants in partially hepatectomized rats implies that the increase in hepatocyte growth factor seen in the plasma is caused by production at extrahepatic site(s). Possible sources include the pancreas, brain, thyroid and salivary glands, and Brunner's glands of the duodenum. Norepinephrine also increases in plasma as early as 2 hr after hepatectomy. In vitro, [3H]thymidine incorporation into hepatocyte DNA in the presence of hepatocyte growth factor is greater if 10(-5) mol/L norepinephrine is also present in the media.(ABSTRACT TRUNCATED AT 250 WORDS)
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              Platelet administration via the portal vein promotes liver regeneration in rats after 70% hepatectomy.

              This study examines the applicability of platelet infusion therapy for liver regeneration in vivo. We recently reported that platelets accumulate in the liver immediately after extended hepatectomy and promote residual liver regeneration. Liver regeneration depends on the number of accumulated platelets in the sinusoids. Male Sprague-Dawley rats underwent 70% hepatectomy and were then assigned to groups that were infused with 1 mL of either platelet-rich plasma (PRP; 1 × 10(9) platelets/mL) in normal saline (NS) or NS via the portal vein. We then analyzed liver regeneration and the signaling pathways that are related to liver regeneration and function. The dynamics of platelets infused via the portal vein were visualized before and after hepatectomy. The liver/body weight ratio after 70% hepatectomy was significantly higher and the Ki-67 labeling index was higher in the PRP, than in the NS group. The Akt pathway was activated earlier in the PRP, than in the NS group with concurrent ERK1/2 pathway activation, but this was prolonged in the PRP group. Many more platelets infused via the portal vein accumulated in the sinusoid after 70% hepatectomy, and serum liver function tests and histological findings revealed that portal infusion did not cause liver damage. Platelets infused via the portal vein promoted liver regeneration after 70% hepatectomy in rats without liver damage. These findings indicate that PRP administration could be a useful part of liver regeneration therapy.
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                Author and article information

                Journal
                Arq Bras Cir Dig
                Arq Bras Cir Dig
                abcd
                Arquivos Brasileiros de Cirurgia Digestiva : ABCD
                Colégio Brasileiro de Cirurgia Digestiva
                0102-6720
                2317-6326
                Apr-Jun 2016
                Apr-Jun 2016
                : 29
                : 2
                : 102-104
                Affiliations
                [1 ]Postgraduate Program in Principles of Surgery, Evangelic Faculty of Paraná/University Evangelic Hospital of Curitiba/Medical Research Institute
                [2 ]Nossa Senhora das Graças Hospital, Curitiba, PR, Brazil.
                Author notes
                Correspondence: Henrique Daga E-mail: henrique.daga@ 123456hotmail.com

                Conflicts of interest: none

                Article
                10.1590/0102-6720201600020009
                4944745
                27438036
                f2f83bd5-4529-497d-92e9-c6431c6e0b47

                This is an open-access article distributed under the terms of the Creative Commons Attribution License

                History
                : 17 December 2015
                : 25 February 2016
                Page count
                Figures: 0, Tables: 6, Equations: 0, References: 21, Pages: 3
                Categories
                Original Article

                tranexamic acid,hepatectomy,liver regeneration
                tranexamic acid, hepatectomy, liver regeneration

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