Angiotensin-converting enzyme inhibition by lisinopril enhances liver regeneration in rats

Bradykinin has been reported to act as a growth factor for fibroblasts, mesangial cells and keratinocytes. Recently, we reported that bradykinin augments liver regeneration after partial hepatectomy in rats. Angiotensin-converting enzyme (ACE) is also a powerful bradykinin-degrading enzyme. We have investigated the effect of ACE inhibition by lisinopril on liver regeneration after partial hepatectomy. Adult male Wistar rats underwent 70 percent partial hepatectomy (PH). The animals received lisinopril at a dose of 1 mg kg body weight-1 day-1, or saline solution, intraperitoneally, for 5 days before hepatectomy, and daily after surgery. Four to six animals from the lisinopril and saline groups were sacrificed at 12, 24, 36, 48, 72, and 120 h after PH. Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen using the PC-10 monoclonal antibody. The value for the lisinopril-treated group was three-fold above the corresponding control at 12 h after PH (P<0.001), remaining elevated at approximately two-fold above control values at 24, 36, 48 (P<0.001), and at 72 h (P<0.01) after PH, but values did not reach statistical difference at 120 h after PH. Plasma ACE activity measured by radioenzymatic assay was significantly higher in the saline group than in the lisinopril-treated group (P<0.001), with 81 percent ACE inhibition. The present study shows that plasma ACE inhibition enhances liver regeneration after PH in rats. Since it was reported that bradykinin also augments liver regeneration after PH, this may explain the liver growth stimulating effect of ACE inhibitors

Efeitos do pré-condicionamento hepático em ratos cirróticos, submetidos à isquemia e reperfusäo hepática: resultados preliminares / Effects of the hepatic preconditioning in rats with liver cirrhosis, submitted to ischemia of the hepatic reperfusion: preliminary result

Baseando-se nos efeitos estimuladores do metabolismo energético pelo pré-condicionamento isquêmico (PCI) no tecido hepático, estudou-se dois grupos de ratos cirróticos submetidos a isquemia de 20 min e reperfusäo de 120 min, após o PCI ou näo respectivamente, determinando assim o valor do seu uso no prolongamento da manobra de Pringle e na regeneraçäo hepática na hepatectomia. Descritores: Cirrose hepática; isquemia hepática; razäo de controle respiratório(RCR); pré-condicionamento isquêmico hepático.

Evoluçäo da fibrose biliar secundária em ratos tratados mediante derivaçäo bílio duodenal ou bíliojejunal com alça de roux medindo 5, 10 e 15 cm / Evolution of secondary biliary fibrosis in rats treated with bile-duodenal shunt or roux-en-y bile-jejunal shunt measuring 5, 10 and 15 centimeters

A modalidade de derivaçäo bílio-digestiva empregada no tratamento da colestase extra-hepática crônica pode influenciar na reparaçäo das lesöes hepáticas. Avaliou-se o desempenho das derivaçöes bílio-duodenal e bílio-jejunal em Y de Roux com alça exclusa de diferentes comprimentos na reparaçäo das lesöes morfológicas e funcionais do fígado de ratos com fibrose biliar secundária. Foram utilizados ratos Wistar, com 15 dias de obstruçäo biliar, alocados em 5 grupos de 6 animais. O grupo OB caracterizou as alteraçöes da fibrose biliar. Os animais remanescentes foram tratados mediante derivaçäo com o duodeno (grupo DBD), e com o jejuno, em alça exclusa de 5cm (grupo DBJ5), 10cm (grupo DBJ10) e 15cm (grupo DBJ15), sendo reavaliados 3 meses depois. Outros 6 animais foram submetidos à inteTodos animais foram submetidos à avaliaçäo morfométrica do fígado, análise bioquímica do sangue e microbiológica da bile, estudo da funçäo mitocondrial hepática e verificaçäo do peso úmido do fígado e do baço. Na análise estatística adotou-se o nível de significância de 5 por cento. Houve aumento significativo do peso estimado, em g/Kg de peso corporal, dos ductos biliares, da fibrose e dos hepatócitos nos animais do grupo OB (medianas de 1,30; 10,03 e 37,0) em relaçäo aos animais controles (IS) (medianas de 0,03; zero e 29,37). Após tratamento, ocorreu regressäo significativa do peso estimado dos ductos biliares e da fibrose, com valores medianos de 0,22 e 0,22 para o grupo DBD, 0,45 e 3,31 para o grupo DBJ5 e 0,22 e 5,0 para o grupo DBJ15. Houve regressäo significativa do peso estimado dos hepatócitos apenas nos grupos derivados com o jejuno, com valores medianos de 31,93; 24,46 e 28,52. Ocorreu aumento significativo do peso úmido do fígado e do baço no grupo OB (medianas em g/Kg de peso corporal de 49,85 e 5,71) em relaçäo ao grupo IS (30,0 e 3,04). Houve regressäo significativa do peso do fígado em todos os tratamentos e do peso do baço nos animais tratados com derivaçäo bílio-jejunal, (valores medianos de 35,59 e 2,53 para DBJ5, 37,54 e 2,82 para DBJ10 e 32,73 e 2,93 para DBJ15). Após o tratamento, surgiram infiltrado inflamatório misto, nos espaços portais, refluxo enterobiliar e contaminaçäo bacteriana da bile. Houve aumento significativo no consumo de oxigênio pela mitocôndrias hepáticas nos estados 3 e 4 no grupo OB (medianas de 101,55 e 31,05 nanoátomos de O2/mgprot./min), em relaçäo ao grupo IS (medianas de 57,22 e 15,51)...

Hepatic morphology changes after hepatic artery ligation in extrahepatic cholestasis

The present study was performed to correlate changes in hepatic morphology with hepatic artery ligation (HAL) in the presence of extrahepatic cholestasis (EHC). The study was conducted on 36 male Wistar rats weighing 350 to 400 g, divided at random into four groups of 9 animals each: group I, sham operation (control); group II, HAL; group III, bile duct ligation (BDL); group IV, HAL plus BDL. After seven days, liver fragments were obtained for morphiological study. The relative volume of the bile ducts was I>IIIV (P<0.05). These data indicate that arterial irrigation is important for the nutrition of the biliary tree. Seventy-six percent of the animals sumitted to HAL plus BDL showed hepatic necrosis. In general, the liver propably becomes more dependent on HA flow in the presence of EHC

Integrity of liver inner mitochondrial membrane in rats with extrahepatic cholestasis

To investigate the effect of extrahepatic cholestasis on integrity of the inner mitochondrial membrane, a study was conduced on two groups of rats: sham-operated control animals (N=10) and rats subjected to extrahepatic cholestasis (EHC, N+10) by double ligation of the hepatic duct. The animals were observed for 7 days and then sacrificed. The EHC group presented significantly hugher serum levels of alanine aminotransferase, total bilirubins and alkakine phosphatase than the controls (P<0.01). Basal mitochondrial respiration (state IV), analyzed separately using either *-ketoglutarate or *-ketoglutarate+ pyruvate as substrates, was similar in the two groups (P>0.01). ADP-activated respiration, state III, dimished significantly in the EHC group. The results show that the decrease in mitochondrial function that has been reported by several investigators to occur in EHC is due to mitochondrial a alterations not related to the ability of these organelles to maintain the proton gradient, since the inner mitochondrial membrane continued to be energized throughtout the observation period