Liver regeneration after extensive hepatectomy in rats: effect of preoperative chemotherapy with intravenous 5-fluorouracil

Purpose: To evaluate the effect of preoperative intravenous chemotherapy with 5-fluorouracil on liver regeneration in an experimental model of major hepatectomy in rats. Methods: Wistar rats were divided into two groups of 20 animals each and submitted to 70% hepatectomy 24 h after intravenous injection of 5-fluorouracil 20 mg/kg (fluorouracil group, FG) or 0.9% saline (control group, CG). After hepatectomy, each group was subdivided into two subgroups of 10 animals each according to the day of sacrifice (24 h or 7 days). Liver weight during regeneration, liver regeneration rate using Kwon formula, and the immunohistochemical markers proliferating cell nuclear antigen (PCNA) and Ki-67 were used to assess liver regeneration. Results: At early phase (24 h after hepatectomy) it was demonstrated the negative effect of 5-fluorouracil on liver regeneration when assessed by Kwon formula (p < 0.0001), PCNA analysis (p = 0.02). With regeneration process complete (7 days), it was possible to demonstrate the sustained impairment of chemotherapy with 5-fluorouracil on hepatocytes regeneration phenomenon when measured by Kwon formula (p = 0.009), PCNA analysis (p = 0.0001) and Ki-67 analysis (0.001). Conclusions: Preoperative chemotherapy with intravenous 5-fluorouracil negatively affected the mechanisms of liver regeneration after major hepatectomy in rats.

Pretreatment of hepatetctomized rats with Coleus forskohlii did not interfere with the course of hepatic hyperplasia

Purpose: Coleus forskohlii Briq., a medicinal plant originally from India, has been indicated against heart disease, expiratory disorders, convulsions, and hepatic changes, among others. In view of the broad pharmacological potential of the plant and the scarce information about its effects, the objective of the present study was to investigate the effect of its use for pretreatment of partially hepatectomized rats. Methods: The animals were divided into two experimental groups: Control (CG) receiving physiological saline for 10 days before partial hepatetctomy, and Treated (TG) receiving 40 mg Coleus forskohlii/kg/day for 10 days before partial hepatectomy. The treatments were performed by gastric gavage. After the surgical procedure, treatment was continued according to the following groups: CG 24 h, CG 48 h, TG 24 h, and TG 48 hs, and liver tissue and intracardiac blood samples were obtained for histological and biochemical analysis, respectively. Results: No significant differences were observed in mitotic or apoptotic index or in the concentrations of the enzymes AST, ALT and alkaline phosphatase, and no areas of fibrosis were detected. Conclusion: Treatment with Coleus forskohlii did not interfere with the course of hepatic hyperplasia.(AU)

Pine (Pinus densiflora) needle extract could promote the expression of PCNA and Ki-67 after partial hepatectomy in rat

Purpose: To investigate the effects of pine needle extract (PNE) on the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 during liver regeneration induced by 70% partial hepatectomy (PH) in rat. Methods: Forty-eight male rats (SD, 7 weeks) had surgery (70% PH). They were randomly divided into two groups. PH + PNE group was only provided PNE diluted in water (10%) for drinking and PH group was provided water from 5 days before surgery to the time of sacrifice. PNE was made by pressing and filtering. Animals were sacrificed at 12h, 24h, 36h, 60h, 84h, 168h after PH, respectively. The expressions of PCNA and Ki-67 were determined as proliferation indices. Results: Immunohistochemistry turned out to increase the expression of PCNA and Ki-67. PCNA expression of PH+PNE group increased up to twice of that of PH group. Western blot also seemed to increase the PCNA expression. These results indicated the promotion of cell proliferation in liver tissue and hepatic regeneration. Conclusions: Pine needle extract stimulates the expression of some mitotic proteins during liver regeneration induced by 70% PH in rats. It suggests that administration of pine needle extract could accelerate the liver regeneration after partial hepatectomy.(AU)

Manejo clínico e cirúrgico de um cão com colangiocarcinoma difuso / Clinical and surgical management of dog with diffuse cholangiocarcinoma

Background: Cholangiocarcinoma is an epithelial cell malignancy arising at various locations within the biliary tree. Primary liver tumors can be classified morphologically as solid, when a single large tumor involves only one liver lobe; nodular, when multiple tumors are located in different liver lobes; diffuse, when either multifocal nodular changes occur in different liver lobes or when diffuse changes occur throughout the liver. Surgery is the treatment of choice for these tumors because there is no established, effective chemotherapy protocol. This paper reports on the management of a dog with diffuse cholangiocarcinoma.Case: A 13-year-old female, castrated Pinscher, weighting 6 kg, was admitted at the Veterinary Medical Teaching Hospital of the Federal University of Rio Grande do Sul (UFRGS) with clinical signs of abdominal distension and dyspnea that had started one month ago. The patient had been subjected to total unilateral mastectomy to remove an adenocarcinoma. At clinical examination, the animal presented anemia, an area of silence during pulmonary auscultation on the right hemithorax, and hepatomegaly. Because of the chronicity and nonspecific signs, additional tests were requested. Abdominal ultrasound exam showed hepatomegaly with irregular echotexture; cavity areas scattered throughout the organ, especially by the right medial lob; discrete presence of free abdominal fluid. Thoracic radiography showed increased radiopacity in the medial and caudal right hemithorax, suggesting metastasis. Laboratory tests included a complete blood count (normocytic mycrocytic anemia), an albumin count (27.49 g/L), an alanine amino-transferase test (77.40 U/L), an alkaline phosphatase test (284.94 U/L), a creatinine test (0.81 mg/dL), a conjugated bilirubin test (0.1 mg/dL), a not conjugated bilirubin test (0.1 mg/dL), and a total bilirubin test (0.2 mg/dL). After blood transfusion, a hepatic lobectomy was performed.[...]

Manejo clínico e cirúrgico de um cão com colangiocarcinoma difuso / Clinical and surgical management of dog with diffuse cholangiocarcinoma

Background: Cholangiocarcinoma is an epithelial cell malignancy arising at various locations within the biliary tree. Primary liver tumors can be classified morphologically as solid, when a single large tumor involves only one liver lobe; nodular, when multiple tumors are located in different liver lobes; diffuse, when either multifocal nodular changes occur in different liver lobes or when diffuse changes occur throughout the liver. Surgery is the treatment of choice for these tumors because there is no established, effective chemotherapy protocol. This paper reports on the management of a dog with diffuse cholangiocarcinoma.Case: A 13-year-old female, castrated Pinscher, weighting 6 kg, was admitted at the Veterinary Medical Teaching Hospital of the Federal University of Rio Grande do Sul (UFRGS) with clinical signs of abdominal distension and dyspnea that had started one month ago. The patient had been subjected to total unilateral mastectomy to remove an adenocarcinoma. At clinical examination, the animal presented anemia, an area of silence during pulmonary auscultation on the right hemithorax, and hepatomegaly. Because of the chronicity and nonspecific signs, additional tests were requested. Abdominal ultrasound exam showed hepatomegaly with irregular echotexture; cavity areas scattered throughout the organ, especially by the right medial lob; discrete presence of free abdominal fluid. Thoracic radiography showed increased radiopacity in the medial and caudal right hemithorax, suggesting metastasis. Laboratory tests included a complete blood count (normocytic mycrocytic anemia), an albumin count (27.49 g/L), an alanine amino-transferase test (77.40 U/L), an alkaline phosphatase test (284.94 U/L), a creatinine test (0.81 mg/dL), a conjugated bilirubin test (0.1 mg/dL), a not conjugated bilirubin test (0.1 mg/dL), and a total bilirubin test (0.2 mg/dL). After blood transfusion, a hepatic lobectomy was performed.[...](AU)

Effects of thymoquinone and curcumin on the regeneration of rat livers subject to 70% hepatectomy

Purpose: To investigate thymoquinone, curcumin and a combination of these two drugs were effective or not at the growth of liver.Methods: Forty female Wistar-Albino rats distributed into five groups of eight rats each, control, thymoquinone, curcumin, and thymoquinone/curcumin groups. Pathological specimens were studied using the Ki-67 Proliferation Index(PI); and arginase(Arg), tissue plasminogen activator(tPA), ceruloplasmin(Cer) and nitric oxide(NO) were studied in biochemical analysis.Results: Our results showed that Ki-67 proliferation index was low in Groups 1. The proliferation coefficient was significantly higher in the Group 2 and Group 4 than in the Group 1 and Group 3.(P < 0.001 between Groups 1 and 2, 1 and 4, and 3 and 4). There was no difference between Groups 2 and 4 (P = 1). The results of the biochemical Arg, tPA and Cer test showed statistically between the Group 1 and Group 2. NO showed significant differences Group 1 and 3.Conclusions: Thymoquinone and curcumin both have known positive effects on the organism. Histological and biochemical tests showed that thymoquinone is more effective than curcumin.(AU)

Capsiate treatment in liver surgeries may compromise its recovery

Purpose: To investigate the effects of capsiate treatment on hepatic hyperplasia in partially hepatectomized rats. Methods: The animals were divided into a Capsiate group (CPH), a Capsiate Post-Partial Hepatectomy group (CPPH) and a Partial Hepatectomy Control group (PH). CPH and CPPH animals received 60 mg/kg/day Capsiate for 30 days. Next, the rats underwent partial hepatectomy. CPPH animals continued to receive treatment for 48 h after partial hepatectomy. Liver tissue and intracardiac blood samples were obtained 24 or 48 h after PH. Results: Capsiate treatment interfered with hepatic parameters, reducing the number of mitoses and apoptosis and increasing blood ALT and alkaline phosphatase concentrations. Conclusion: Capsiate treatment preceding hepatic surgery may compromise the initial period of postoperative recovery.(AU)

Intravascular and intraparenchymatous hepatic segmentary sclerosis

Purpose: To evaluate the morphological effects of injected sclerosing agents into the liver. Methods: This study was performed on twenty dogs, distributed into five groups: Group 1 (n = 5) - control, Group 2 (n = 5) - injection of 50% glucose solution inside hepatic parenchyma and animals followed during seven days, Group 3 (n = 10) - injection of ethanol inside hepatic parenchyma and animals distribution into two subgroups Subgroup 3A (n = 5) - followed during 24 hours and subgroup 3B (n = 5) - followed during seven days (group 3B), Group 4 (n = 5) - ethanol injection inside left portal vein branch and followed during 24 hours. Livers were macroscopically evaluated, submitted to hepatic arteriography and portography, then histology. Results: All animals in Group 4 died within 23 hours due to diffuse hepatic necrosis. The animals of groups 2 and 3 had a satisfactory evolution. Fibrosis formed in the segment reached by the sclerosant solution and interruption of the contrast flow injected into the portal system. Conclusion: Intrahepatic parenchymal ethanol injection is well tolerated and causes sclerosis restricted to a specific segment; however, intraportal ethanol injection causes massive hepatic necrosis and can lead to death.(AU)

Lycopene and resveratrol pretreatment did not interfere with the liver of hepatectomized rats

Purpose: To investigate the effects of lycopene and resveratrol pretreatment on hepatic hyperplasia in partially hepatectomized rats. Methods: The lycopene group and the resveratrol group received 40 mg/kg/day of lycopene or resveratrol, respectively (dissolved in olive oil or in saline solution, respectively) and administered via a gastric tube for 30 days. The partially hepatectomzed (PH) control groups received saline or olive oil via a gastric tube for 30 days, respectively, and the normal control group received no treatment. Liver tissue and intracardiac blood samples were obtained 24, 36 or 48 h after PH. Results: No areas of fibrosis were detected. No significant changes in mitotic index, in the number of apoptosis events or in aspartate aminotransferase and alanine aminotransferase levels were observed. Conclusions: Lycopene and resveratrol pretreatment did not interfere on hepatic hyperplasia in partially hepatectomized rats.(AU)

Effect of aqueous extract of the leaves of Baccharis trimera on the proliferation of hepatocytes after partial hepatectomy in rats

Purpose: To evaluate the effect of aqueous extract of Baccharis trimera leaves on the proliferative capacity of the liver after partial hepatectomy (PH) in rats. Methods: Twenty Wistar rats weighing between 300 and 450g were divided into two groups: control (HP) and test (HP100-rats that received the aqueous extract of Baccharis trimera for four days at a dose of 100 mg / kg / day). On the fifth day, animals from both groups underwent resection of 70% of the liver. Twenty-four hours later, they were sacrificed and the remnant liver was removed and prepared for studied through PCNA immunohistochemistry. Data analysis for comparison between the two groups was made through the non-parametric statistical test Mann-Whitney test. Results: In all the animals studied was found most abundant nuclear immunostaining positive hepatocytes interlobular located in regions of the liver. Quantitative analysis of PCNA-positive cells revealed positivity rate significantly higher mean (p = 0.02) in HP100 group (77.1 ± 13.6) compared to the HP group (45.8 ± 12.9). Conclusion: DAdministration of aqueous extract of the leaves of Baccharis trimera 100 mg/kg of animal has a significant positive effect on liver regeneration in rats, 24 hours after hepatectomy (70%).(AU)

Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy?

Purpose: To evaluate the effects of mesenchymal stem cells on liver regeneration in rats following a 70% hepatectomy. Methods: Forty rats were subjected to 70% hepatectomy and then ~106 mesenchymal stem cells (test group), or saline solution (control group), were infused into their livers via the portal vein. Each treatment group was divided into early and late subgroups (euthanized 3 d and 5 d following the operation, respectively). Group comparisons of Albumin, aminotransaminases (AST, ALT), and Alcaline Phosphatase (AP) levels, proliferative index (ki-67+ straining), and mitotic cell counts were conducted. Results: No significant differences in liver regeneration rate, number of mitoses, proliferative index, or serum levels of albumin, AST, or AP were observed. ALT levels were higher in the test group than in the control group (p .05). Conclusions: Mesenchymal stem-cell therapy did not improve liver regeneration rate 3 d or 5 d after 70% hepatectomy in rats. Likewise, the therapy appeared not to affect liver function, proliferative index, or number of mitoses significantly.(AU)

Propofol attenuates cytokine-mediated upregulation of expression of inducible nitric oxide synthase and apoptosis during regeneration post-partial hepatectomy

Purpose: To determine the effects of propofol and ketamine anesthesia on liver regeneration in rats after partial hepatectomy (PHT). Methods: Male Wistar albino rats were assigned randomly to four groups of 10. Anesthesia was induced and maintained with propofol in groups 1 and 2, and with ketamine in groups 3 and 4. PHT was undertaken in groups 1 and 3. Rats in groups 2 and 4 (control groups) underwent an identical surgical procedure, but without PHT. At postoperative day-5, rats were killed. Regenerated liver was removed, weighed, and evaluated (by immunohistochemical means) for expression of inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), apoptosis protease-activating factor (APAF)-1, and proliferating cell nuclear antigen (PCNA). Also, blood samples were collected for measurement of levels of tumor necrosis factor (TNF)- and interleukin (IL)-6. Results: Between groups 2 and 4, there were no differences in tissue levels of iNOS, eNOS, and APAF-1 or plasma levels of TNF- and IL-6. eNOS expression was similar in group 1 and group 3. Expression of iNOS and APAF-1 was mild-to-moderate in group 1, but significantly higher in group 3. Groups 1 and 3 showed an increase in PCNA expression, but expression in both groups was comparable. Plasma levels of TNF- and IL-6 increased to a lesser degree in group 1 than in group 3. Conclusion: Propofol, as an anesthetic agent, may attenuate cytokine-mediated upregulation of iNOS expression and apoptosis in an animal model of liver regeneration after partial hepatectomy.(AU)

The effect of the aqueous extract Peumus boldus on the proliferation of hepatocytes and liver function in rats submitted to expanded hepatectomy

PURPOSE: To assess the effect of aqueous extract of Peumus Boldus (AEPB) on the liver proliferative response after parcial hepatectomy of 70% (PH) in rodents. METHODS: Twenty Wistar rats were divided in two groups: AEPB100 (whose rats received 100mg/Kg of AEPB, once a day, orally, in 4 days prior to the first surgical procedure) and Vehicle (whose rats were treated similarly with distilled water). Both groups underwent PH. After 24 hours the remaining livers were removed for studying the proliferation of hepatocytes by Ki-67 and 2mL of blood were collected for serological assessment: cholesterol, glucose, triglycerides, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total, direct and indirect bilirubin. All data were analyzed by Gaussian distribution. Statistically significant differences between mean values were analyzed using T Student's test. Non-Gaussian data were analyzed using Mann-Whitney's test. RESULTS: The liver of all these rats presented positive staining of Ki-67, indicating liver proliferation. Laboratory results showed no significant difference in serum values between the analyzed groups. The analysis of Ki-67 was significantly more positive in AEPB100 group than in Vehicle group. CONCLUSION: Aqueous extract of Peumus Boldus acute administration exerts significant positive effect on liver regeneration after 24h in rats that underwent parcial hepatectomy, while maintaining unchanged hepatic function.(AU)

Partial hepatectomy in a calf with an omphalocele: case report / Hepatectomia parcial em bezerra portadora de onfalocele: relato de caso

An omphalocele is a defect in the closure of the abdominal wall during the embryonic stage, preventing the return of some abdominal organs to the cavity. In stillborn animals, the involvement of the liver in the omphalocele has been reported. The aim of the present study is to report the success of a partial liver resection in a female bovine at two days of age which presented an omphalocele at birth. Surgical intervention was indicated to reduce and suture the abdominal wall. During the surgical procedure, the presence of hard, reddish tissue was noted inside the sac covered by the amniotic membrane, with characteristics consistent with hepatic parenchyma. Due to the impossibility of reducing the contents added to the suggestion of tissue infection, we elected to perform a partial resection. The histopathological examination confirmed that the resected tissue was of the hepatic parenchyma. Antibiotic and systemic anti-inflammatory therapies were performed post-surgery. Fifteen days after surgery, infection was detected at the surgical site in addition to abdominal wound dehiscence; surgical reintervention was performed. On physical examination, carried out 4 months after the second operation, the heifer presented normal development for the species. In conclusion, omphalocele may contain liver. Ectopic liver is an extremely rare condition. Surgical treatment in the presented case focused on umbilicus with exploration of the abdominal cavity appeared to be sufficient.(AU)

A onfalocele é um defeito no fechamento da parede abdominal durante a fase embrionária, não permitindo o retorno de alguns órgãos abdominais à cavidade. O envolvimento do fígado em onfalocele tem sido relatado, porém em animais natimortos. Com o presente estudo, objetiva-se relatar uma ressecção parcial do fígado realizada com sucesso em uma fêmea bovina com dois dias de idade apresentando onfalocele ao nascimento. Foi indicada a intervenção cirúrgica para a redução e rafia da parede abdominal. Durante o procedimento cirúrgico, notou-se, no interior do saco recoberto pela membrana amniótica, a presença de tecido firme, de coloração avermelhada, com características compatíveis com parênquima hepático. Devido à impossibilidade de redução do conteúdo e sugestão de infecção do tecido encontrado, optou-se pela ressecção parcial dele. O exame histopatológico confirmou tratar-se de parênquima hepático o tecido resseccionado. No pós-cirúrgico, realizaram-se terapias antibiótica e antiinflamatória sistêmicas. Após 15 dias do procedimento cirúrgico, foi detectada infecção do sítio operatório e deiscência da sutura abdominal, sendo realizada reintervenção cirúrgica. No exame físico, realizado no animal após quatro meses da segunda intervenção cirúrgica, constatou-se desenvolvimento normal para a espécie. Conclui-se que o fígado pode ser conteúdo da onfalolocele, sendo uma condição extremamente rara. O tratamento cirúrgico no caso apresentado, com exploração da cicatriz umbilical e da cavidade abdominal, foi suficiente.(AU)

Partial hepatectomy in a calf with an omphalocele: case report / Hepatectomia parcial em bezerra portadora de onfalocele: relato de caso

An omphalocele is a defect in the closure of the abdominal wall during the embryonic stage, preventing the return of some abdominal organs to the cavity. In stillborn animals, the involvement of the liver in the omphalocele has been reported. The aim of the present study is to report the success of a partial liver resection in a female bovine at two days of age which presented an omphalocele at birth. Surgical intervention was indicated to reduce and suture the abdominal wall. During the surgical procedure, the presence of hard, reddish tissue was noted inside the sac covered by the amniotic membrane, with characteristics consistent with hepatic parenchyma. Due to the impossibility of reducing the contents added to the suggestion of tissue infection, we elected to perform a partial resection. The histopathological examination confirmed that the resected tissue was of the hepatic parenchyma. Antibiotic and systemic anti-inflammatory therapies were performed post-surgery. Fifteen days after surgery, infection was detected at the surgical site in addition to abdominal wound dehiscence; surgical reintervention was performed. On physical examination, carried out 4 months after the second operation, the heifer presented normal development for the species. In conclusion, omphalocele may contain liver. Ectopic liver is an extremely rare condition. Surgical treatment in the presented case focused on umbilicus with exploration of the abdominal cavity appeared to be sufficient.(AU)

A onfalocele é um defeito no fechamento da parede abdominal durante a fase embrionária, não permitindo o retorno de alguns órgãos abdominais à cavidade. O envolvimento do fígado em onfalocele tem sido relatado, porém em animais natimortos. Com o presente estudo, objetiva-se relatar uma ressecção parcial do fígado realizada com sucesso em uma fêmea bovina com dois dias de idade apresentando onfalocele ao nascimento. Foi indicada a intervenção cirúrgica para a redução e rafia da parede abdominal. Durante o procedimento cirúrgico, notou-se, no interior do saco recoberto pela membrana amniótica, a presença de tecido firme, de coloração avermelhada, com características compatíveis com parênquima hepático. Devido à impossibilidade de redução do conteúdo e sugestão de infecção do tecido encontrado, optou-se pela ressecção parcial dele. O exame histopatológico confirmou tratar-se de parênquima hepático o tecido resseccionado. No pós-cirúrgico, realizaram-se terapias antibiótica e antiinflamatória sistêmicas. Após 15 dias do procedimento cirúrgico, foi detectada infecção do sítio operatório e deiscência da sutura abdominal, sendo realizada reintervenção cirúrgica. No exame físico, realizado no animal após quatro meses da segunda intervenção cirúrgica, constatou-se desenvolvimento normal para a espécie. Conclui-se que o fígado pode ser conteúdo da onfalolocele, sendo uma condição extremamente rara. O tratamento cirúrgico no caso apresentado, com exploração da cicatriz umbilical e da cavidade abdominal, foi suficiente.(AU)

Which is the best route of administration for cell therapy in experimental model of small-for size syndrome in rats?

PURPOSE: To evaluate which is the best route of administration for cell therapy in experimental rat model of small-for size syndrome. METHODS: A total of 40 rats underwent partial hepatectomy (70%) that induces the small-for-size syndrome and were divided into four groups of route administration: intravenous, intraperitoneal, enteral and tracheal. The small-for-size syndrome model was designed with extended partial hepatectomy (70%). The animals were divided into four groups of routes administration: intravenous (n=10) - intravenously through the dorsal vein of the penis; intraperitoneal (n=10) - intraperitoneally in the abdominal cavity; enteral (n=10) - oroenteral with the placement of a number 4 urethral probe and maintained at third duodenal portion; tracheal (n=10) - after tracheal intubation. We track the animals and monitor them for 21 days; during this follow-up we evaluated the result of cell therapy application tracking animals using ultrasound, radiography and PET-scan. Statistical analysis was performed using GraphPad Prism Software®. Differences were considered significant with the p<0.05. Data are presented as the median and variation for continuous variables. Comparisons between groups were made using analysis of the imaging test by the researchers. RESULTS: All four groups underwent partial hepatectomy of 70% liver tissue targeting the same weight of resected liver. Initially the PET-scan tests showed similarity in administered cells by different routes. However, in few days the route of intravenous administration showed to be the most appropriated to lead cells to the liver followed by enteral. The tracheal and peritoneal routes were not as much successful for this goal.(AU)

Effect of cyclosporine on liver regeneration in partial hepatectomized rats

PURPOSE: To evaluate the influence of the cyclosporine in liver regeneration in rats submitted to an experimental model of 70% hepatectomy. METHODS: Forty male rats were randomly divided in four subgroups (C.24h, C.7d, E.24h, E.7d), according to the drug used and the day of sacrifice (24 hours and 7 days). Cyclosporine (10mg/Kg/day) was given to the study subgroup and 1 ml of 0.9% sodium chloride was to the control subgroup. Resection of left lateral lobe and median lobe performing 70% of liver mass. During the animals death, KWON formula was applied. Counting of mitotic figures and percentage of positive nucleus with PCNA and Ki-67 were evaluated. RESULTS: In the 2nd, 4th PO and death days, E.7d lose more weight than C.7d. Regarding to the KWON formula, the C.7d regenerated more than the C.24h and the same with the E.7d. Comparing between the groups, only E7d subgroup was statistically significant compared with C.7d, showing the stimulating effect of cyclosporine in liver regeneration. Immunohistochemestry had significant results between the study subgroups. The mitotic index revealed statistical differences in the control subgroups. CONCLUSION: Cyclosporine, in spite of being an immunosuppressive drug, has a positive effect in liver regeneration, although reduce the animals body weight.(AU)

Glutamine and ornithine alpha-ketoglutarate supplementation on malate dehydrogenases expression in hepatectomized rats

To evaluate the relative gene expression (RGE) of cytosolic (MDH1) and mitochondrial (MDH2) malate dehydrogenases enzymes in partially hepatectomized rats after glutamine (GLN) or ornithine alpha-ketoglutarate (OKG) suplementation. One-hundred and eight male Wistar rats were randomly distributed into six groups (n=18): CCaL, GLNL and OKGL and fed calcium caseinate (CCa), GLN and OKG, 0.5g/Kg by gavage, 30 minutes before laparotomy. CCaH, GLNH and OKGH groups were likewise fed 30 minutes before 70% partial hepatectomy. Blood and liver samples were collected three, seven and 14 days after laparotomy/hepatectomy for quantification of MDH1/MDH2 enzymes using the real-time polymerase chain reaction (PCR) methodology. Relative enzymes expression was calculated by the 2-ΔΔC T method using the threshold cycle (CT) value for normalization. MDH1/MDH2 RGE was not different in hepatectomized rats treated with OKG compared to rats treated with CCa. However, MDH1/MDH2 RGE was greater on days 3 (321:1/26.48:1) and 7 (2.12:1/2.48:1) while MDH2 RGE was greater on day 14 (7.79:1) in hepatectomized rats treated with GLN compared to control animals. CONCLUSION: Glutamine has beneficial effects in liver regeneration in rats by promoting an up-regulation of the MDH1 and MDH2 relative gene expression.(AU)

Evaluation of liver regeneration with use of diet supplemented with l-arginine

PURPOSE:To compare controlled liver regeneration in rats submitted to 60% hepatic resection having L-arginine supplemented diet, based on weight changes of the regenerated liver, laboratory parameters of liver function and pathological findings.METHODS:Thirty-six rats were divided into two groups, control and L- arginine. The first received standard chow and saline solution by gavage. The second had supplementation with L- arginine. Animals were killed on postoperative period at 24h, 72h and seven days. For analysis of liver regeneration was used Kwon formula for weight, laboratory tests and mitosis.RESULTS:Weight, showed no benefit with L- arginine supplementation; however, intergroup comparison in the first 24h observed positive effect on supplementation (p=0.008). Alkaline phosphatase was increased in arginine group (p<0.04). The number of mitoses showed no difference between the two groups; however, in the first 24 hours, the supplemented group had higher number of mitoses within the groups (p=0.03).CONCLUSION:Supplementation with L-arginine did not show benefits in liver regeneration; however, supplemented group in the first 24 hours showed benefits over 72 hours and seven days of the evaluation by weight gain and number of mitosis.(AU)

The ileum positively regulates hepatic regeneration in rats

To test the hypothesis that liver regeneration after partial hepatectomy can be influenced by the ileum. METHODS: Eighteen Wistar rats were distributed into groups of six animals: 1 - ileum resection+ hepatectomy 2/3; 2 - hepatectomy 2/3, and 3 - sham. Anesthesia with ketamine and xylazine i.p., aseptic technique, analgesia with meperidine (10mg/kg s.c.). On day 6, serum ALT, AST, alkaline phosphatase (AP) and albumin were measured. Liver regeneration and hepatocyte mitosis were quantified. Statistical analysis with ANOVA and Tukey tests, with significance p<0.05. RESULTS: In group hepatectomy+ileal resection, ALT, AST and AP were 180.6±24.9, 58.6±3.1 and 254.6±46.6 respectively. They were significantly higher than in the hepatectomy group, whose values were 126.0±16.5, 44.1±3.9 and 163.5±8.6, respectively (p<0.001). Albumin levels were not significantly different among groups. Liver regeneration in hepatectomy group (94.17%) was statistically higher (p<0.001) than in ileal resection+hepatectomy group (55.96%). In the latter group the mitosis of hepatocytes were significantly less frequent than in the hepatectomy group. CONCLUSION: The data confirm that the ileum positively influence on liver regeneration in rats undergoing hepatectomy.(AU)