Proteçäo funcional do rim com lovastatina após isquemia e reperfusäo renal / Renal functional protection with lovastatin after kidney ischemia-reperfusion

Introduçäo - a isquemia renal é causa de graves lesöes nesse órgäo, estando presente em diferentes situaçöes como em cirurgias renais, vasculares e no transplante renal. Assim, a procura de substâncias protetoras da funçäo renal tem amplo interesse clínico. Neste estudo o objetivo foi o de analisar o efeito da lovastatina na isquemia renal normotérmica seguida da reperfusäo.

Swelling mitocondrial em amostras teciduais de gatos submetidos à oclusäo da artéria cerebral média / Mitochondrial swelling in tissue samples of cats submited to oclusion of middle cerebral artery

A isquemia cerebral tem sido largamente estudada com intuito de se obter medidas terapêuticas eficazes que minimizem seus efeitos, visto que uma grande quantidade de pacientes, clínicos ou cirúrgicos, apresentam conseqüências freqüentemente irreversíveis da mesma. A escolha de um modelo experimental satisfatório a fim de nortear pesquisas com agentes neuroprotetores tem sido a base desses estudos. No presente trabalho foi escolhido o gato como modelo experimental de isquemia e a avaliaçäo foi realizada através do swelling mitocondrial. Os trinta e dois animais utilizados neste experimento, foram divididos em quatro grupos distintos, cada qual com dez animais sendo submetido a um tempo de isquemia, que aumentou progressivamente (15, 30 e 60 minutos), exceto no último grupo com dois animais e que näo foi submetido a nenhum procedimento isquemiante. Foram observadas alteraçöes evidentes nas curvas de swelling mitocondrial energizado nos animais submetidos a 60 minutos de isquemia, quando se comparou amostras do lado isquêmico em relaçäo ao controle, isto ficou ainda mais claro quando se adicionou o antibiótico Alameticina durante os ensaios laboratoriais do swelling mitocondrial. Foi possível chegar às seguintes conclusöes: o swelling funciona como indicador de diferenciaçäo mitocondrial entre diversos tecidos; a mitocôndria do cérebro, quando exposta ao efeito da Alameticina, apresenta uma sensibilidade diferenciada em relaçäo às dos outros tecidos; a mitocôndria do cérebro submetido a isquemia durante 60 minutos se torna mais sensível à Alameticina; e finalmente, as mitocôndrias do cérebro apresentam uma instalaçäo extremamente rápida da reversäo do swelling.

Clorpromazina e funçäo mitocondrial na isquemia-reperfusäo renal / Chlorpromazine and mitochondrial function in kidney ischemia-reperfusion

Introduçäo e objetivo - em transplante renal com doador cadáver, a funçäo do enxerto depende da manutençäo da integridade celular e subcelular, principalmente mitocondrial. Neste estudo o objetivo foi analisar a funçäo mitocondrial do rins submetidos a período prolongado de isquemia fria, seguido de reperfusäo por uma hora, empregando-se, ou näo, a clorpromazina previamente à isquemia. Métodos - utilizando autotransplante renal em cäes, subdivididos em dois grupos, foram extraidas mitocôndrias de rins submetidos à isquemia fria de 48 horas, seguida de 1 hora de reperfusäo pós-transplante. Um grupo recebeu clorpromazina antes da nefrectomia. A análise da fosforilaçäo oxidativa e do intumescimento osmótico ("swelling") mitocôndrial foi comparada com dados obtidos de rins normais, sem isquemia. Resultados - Os dados obtidos para o estado III e IV da respiraçäo näo mostraram diferença significativa entre os grupos experimentais. A primeira fase do "swelling" ocorreu em tempo semelhante em todos os grupos experimentais. Durante a reversäo, os grupos I e II se comportaram de maneira estatisticamente semelhante, com fraçöes de reversäo de 57 por cento, e 68 por cento, respectivamente, valores significativamente menores que os obtidos para o grupo normal (99 por cento) (grupo I: p = 0,0374 e grupo II: p = 0,0221). Discussäo - é conhecida a açäo protetora da clorpromazina na isquemia renal normotérmica. Entretanto, os dados aqui obtidos mostram que após 48 horas de isquemia fria, o grupo II (clorpromazina) comportou-se de maneira semelhante ao grupo I (hipotermia isolada) tanto no estudo da fosforilaçäo oxidativa, quanto no "swelling", embora os valores apresentem tendência a serem maiores no grupo II. Isto pode ser devido a alguns fatores, como: 1) a clorpromazina possui efeito protetor mínimo quando o tempo de isquemia é prolongado; 2) seu efeito pode ser afetado ou sua açäo protetora sobreposta àquela imposta pela hipotermia; 3) tempo de reperfusäo curto para manifestaçäo de seus efeitos.

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

Intramitochondrial calcium and magnesium levels in skeletal muscle submitted to total or partial limb ischemia

Sekeletal muscle temperature and mitochondrial content of Ca2 and Mg2+ were measured after 3 h of total or partial limb ischemia in male Wistar rats (250-350g). The decreases in biceps muscle temperature, measured with a needle thermistor (4.4 ñ 0.26-C (31 rats) in partial ischemia (PI, aorta clamp) and total ischemia (TI, hind leg tourniquet), respectively) were consistent with the expected extente of blood flow reduction for the two ischemic conditions. Mitochondrial calcium levels increased after partial ischemia from 2.67 ñ 0.13 (46 rats) to 4.65 ñ 0.38 (12 rats) nmol/mg protein and increased to 7.87 ñ 0.68 (14 rats) after total ischemia (P<0.05). In contrast, mitochondrial magnesium decreased after partial ischemia from 10.14 ñ 0.35 to 8.22 ñ0.28 (13 rats) but increased in the mitochondria of muscle submitted to total ischemia to 12.0 ñ 0.80 (14 rats; P < 0.05). No changes were observed in the number of binding sites for safranine which competes for calcium binding sites on the inner mitochondrial membrane (25.46 ñ 0.38 nmol/mg protein for sham (20 rats) and 25 ñ 0.68 (7 rats) for PI and 25 ñ 0.31 (5 rats) for TI). The data suggest that the greater resistance of rats muscle to total than to partial ischemia may be due at least in part to the increased mitochondrial Mg2+ content

Serum transaminase levels in the acute phase of chronic extrahepatic cholestasis

Serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) levels are normal or discretely increased in rats with chronic extrahepatic cholestasis (CEHC). During the acute phase (first 72 h after biliary obstruction), however, serum transminase values are quite elevated due to a mechanism not yet fully elucidated. Thus, this is a good experimental model, not involving hepatocellular necrosis, for the study of serum ALT and AST levels during the acute phase of CEHC. Male Wistar rats (250-350 g) were divided into two groups: group A(N = 60) was submitted to sham operation for bile duct ligation (BDL), and group B (N = 60) was submitted to BDL. Thirty and 120 min after BDL there was a 1.5-fold increase in both serum ALT and AST levels compared to sham-operated rats (P<0.05). Serum ALT levels were higher than AST levels as early as 30 min after BDL and the highest serum values for both transaminases were observed at 360 min which was also the last value measured. Serum AST levels increased 120 min after BDL, with no further significant increase thereafter

Effect of hepatic artery ligation in rats with chronic extrahepatic cholestasis

Because of the liver's dependence on arterial blood to exert metabolic functions in cirrhosis of the liver, this or without thrombosis of the portal vein, the interruption of hepatic arterial flow for the pallitive treatment of malignant tumors of the liver is counterindicated. However, the effects of arterial devascularization on the cholestatic liver are not fully understood. The objective of the present study was to investigate hepatic alterations due to hepatic artery ligation in rats with chroni extrahepatic cholestasis. Serum alkaline phosphatase, bilirubin and alanine aminotransferase were measured in rats 3 h after sham operation (group A, N = 29) or ligation of the hepatic artery (group B, N = 29). Alamine aminotransferase activity was significanty higher (P < 0.05) in group B, demonstrating acute hepatocellular damage in animals with chronic extrahepatic cholestasis

Hight chlorpromazine doses and liver function

The aim of the present study was to evaluate the in vivo effect of high chlorpromazine (CPZ) doses on hepatocellular function. Thirty male Wistar rats weighing 200 to 250 g were divided into two groups: control (C, N = 17), injected ip with saline, and CPZ (N = 13), injected ip with high chlorpromazine doses (initial dose of 30 mg/Kg body weight followed by daily doses of 10 mg/Kg for 7 days). No significant differences in serum levels of alanine-aminotransferase, alkaline phosphatase and bilirubin or in mitochondrial function (activated and basal respiration and mitochondrial respiration control(activated/basal ratio) were detected between the two groups

Effect of chlorpromazine and biliary drainage on portal blood flow and mitochondrial function during extrahepatic cholestasis

The present study examines the effect of chlorpromazine and biliary drainage in cholestatic rats. The time course of portal blood flow was studied 24,48, and 72 h and seven days after bile duct ligation. Portal blood flow decreased after 72 h. Chlorpromazine reduced biliary hydrostatic pressure in sham-operated control rats, but 24-h obstruction was sufficient to prevent this effect in cholestatic rats. The drug ameliorated the mitochondrial and cell membrane function of cholestatic rats before and after drainage. The data present further support for the role of ischemia in cholestasis