Effects of a high fat diet on liver mitochondria: increased ATP-sensitive K(+) channel activity and reactive oxygen species generation

High fat diets are extensively associated with health complications within the spectrum of the metabolic syndrome. Some of the most prevalent of these pathologies, often observed early in the development of high-fat dietary complications, are non-alcoholic fatty liver diseases. Mitochondrial bioenergetics and redox state changes are also widely associated with alterations within the metabolic syndrome. We investigated the mitochondrial effects of a high fat diet leading to non-alcoholic fatty liver disease in mice. We found that the diet does not substantially alter respiratory rates, ADP/O ratios or membrane potentials of isolated liver mitochondria. However, H(2)O(2) release using different substrates and ATP-sensitive K(+) transport activities are increased in mitochondria from animals on high fat diets. The increase in H(2)O(2) release rates was observed with different respiratory substrates and was not altered by modulators of mitochondrial ATP-sensitive K(+) channels, indicating it was not related to an observed increase in K(+) transport. Altogether, we demonstrate that mitochondria from animals with diet-induced steatosis do not present significant bioenergetic changes, but display altered ion transport and increased oxidant generation. This is the first evidence, to our knowledge, that ATP-sensitive K(+) transport in mitochondria can be modulated by diet.

Fatores de risco para óbito precoce em crianças e em adolescentes submetidos a tranplante hepático eletivo no Hospital de Clínicas de Porto Alegre

No próximo ano, completam-se 40 anos desde a primeira tentativa de transplante hepático (TxH) em seres humanos. Há quase 20 anos, o transplante (Tx) tornou-se uma opção terapêutica real para os pacientes portadores de doença hepática terminal. Atualmente, o TxH é o tratamento de escolha para diversas enfermidades hepáticas, agudas ou crônicas. Dos transplantes realizados na Europa ou nos EUA, em torno de 12% dos pacientes são crianças e adolescentes. No Brasil, 20,9% dos pacientes transplantados de fígado em 2001 tinham até 18 anos de idade e, destes, 60,7% tinham 5 anos ou menos. O objetivo do TxH é a manutenção da vida dos pacientes com doença hepática irreversível, e a principal forma de avaliação de sucesso é a sobrevida após o Tx. A primeira semana que se segue ao TxH, apesar dos excelentes progressos dos últimos anos, continua sendo o período mais crítico. A maioria dos óbitos ou das perdas do enxerto ocorrem nas primeiras semanas, em particular, nos primeiros 7 dias de TxH. Diversos fatores de risco para o resultado do TxH podem ser identificados na literatura, porém há poucos estudos específicos do Tx pediátrico. As crianças pequenas apresentam características particulares que os diferenciam do Tx nos adultos e nas crianças maiores. Com o objetivo de identificar fatores de risco para o óbito nos 7 primeiros dias após os transplantes hepáticos eletivos realizados em 45 crianças e adolescentes no Hospital de Clínicas de Porto Alegre entre março de 1995 e agosto de 2001, foi realizado um estudo de caso-controle. Entre os 6 casos (13,3%) e os 39 controles foram comparadas características relacionadas ao receptor, ao doador e ao procedimento cirúrgico e modelos prognósticos. Das variáveis relacionadas ao receptor, o gênero, o escore Z do peso e da estatura para a idade, a atresia de vias biliares, a cirurgia abdominal prévia, a cirurgia de Kasai, a história de ascite, de peritonite bacteriana espontânea, de hemorragia digestiva e de síndrome hepatopulmonar, a albuminemia, o INR, o tempo de tromboplastina parcial ativada e o fator V não foram associados com o óbito na primeira semana. A mortalidade inicial foi maior nas crianças com menor idade (p=0,0035), peso (p=0,0062) e estatura (p<0,0001), bilirrubinemia total (BT) (p=0,0083) e bilirrubinemia não conjugada (BNC) (p=0,0024) elevadas, e colesterolemia reduzida (p=0,0385). Os receptores menores de 3 anos tiveram um risco 25,5 vezes maior de óbito que as crianças maiores (IC 95%: 1,3–487,7). A chance de óbito após o Tx dos pacientes com BT superior a 20 mg/dL e BNC maior que 6 mg/dL foi 7,8 (IC95%: 1,2–50,1) e 12,7 (IC95%: 1,3–121,7) vezes maior que daqueles com níveis inferiores, respectivamente. Das características relacionadas ao doador e ao Tx, as variáveis gênero, doador de gênero e grupo sangüíneo ABO não idênticos ao do receptor, razão peso do doador/receptor, causa do óbito do doador, enxerto reduzido, tempo em lista de espera e experiência do Programa não foram associados com o óbito nos primeiros 7 dias. Transplantes com enxertos de doadores de idade até 3 anos, ou de peso até 12 Kg representaram risco para o óbito dos receptores 6,8 (IC95%: 1,1–43,5) e 19,3 (IC95%: 1,3–281,6) vezes maior, respectivamente. O tempo de isquemia total foi em média de 2 horas maior nos transplantes dos receptores não sobreviventes (p=0,0316). Os modelos prognósticos Child-Pugh, Rodeck e UNOS não foram preditivos do óbito. Os pacientes classificados como alto risco no modelo de Malatack apresentaram razão de chances para o óbito 18,0 (IC95%: 1,2–262,7) vezes maior que aqueles com baixo risco. A mortalidade na primeira semana foi associada a valores elevados do escore PELD. O risco de óbito foi de 11,3 (IC95%: 1,2–107,0) nas crianças com valor do PELD maior que 10. As crianças pequenas e com maior disfunção hepática apresentaram maior risco de óbito precoce. Doador de pequeno porte e prolongamento do tempo de isquemia também foram associados à mortalidade. Somente os modelos de Malatack e PELD foram preditivos da sobrevida.

The ileum as a determinant organ of the functional liver cell mass in rats

PURPOSE: To evaluate if the ileum resection changes the functioning liver cell mass, the hepatic metabolism and the biodistribution of radiopharmaceutical in rats. METHODS: Twelve Wistar rats weighing 285g±34g were randomly divided into the ileum resection group (n = 6) and sham group rats (n = 6). After 30 days, they were anesthetized and 0.1mL of 99m-Tc-phytate(0.66MBq) was injected via femoral vein. After 30 minutes, blood samples were collected for red blood cells radioactive labeling and serum ALT, AST and gammaGT. Liver samples were used for 99m-Tc-phytatepercentage of radioactivity/gram of tissue and histopathology. Student’s t test was used with significance 0.05. RESULTS: There was a higher uptake of 99m-Tc-phytate in the liver of sham rats, compared to the ileum resection group (p<0.05). GammaGT, ALT and AST were increased in ileum resection rats compared to sham (p<0.05). The he patocytes count was significantly lower in ileum resection group than in sham (p<0.05). Liver: body mass ratio was lower in experimental animals than in sham group (p<0.05). CONCLUSION: These data support that the ileum has important role in liver function and liver mass regulation, and they have potential clinical implications regarding the pathogenesis of liver injury following lower bowel resection.

Effect of heat stress or lipopolysaccharide (E-coli) injection on HSP70 levels in the liver and brain of adrenalectomized rats

Hsp70 content (ng Hsp70 mu g total protein(-1)) in the liver and brain of control and adrenalectomized male rats was investigated by Western Blotting after heat stress (40 degrees C) or endotoxin-induced fever (E. coli lipopolysaccharide injection). The increase in rectal temperature was higher after heat stress than after LPS injection, Heat stress affected Hsp70 content of the liver, but not of the brain; however adrenalectomy did not influence any parameter. These results suggest that, under these circumstances, there is no relationship between the hypothalamic-pituitary-adrenal axis and Hsp70 synthesis in liver and brain. (C) 2000 Elsevier B.V. Ltd. All rights reserved.

Hematological values and body, heart and liver weights of male and female broiler embryos of young and old breeder eggs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphometry of megakaryocytes in the liver of New Zealand White rabbits during intrauterine and postnatal development

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efficiency of intermittent exercise on adiposity and fatty liver in rats fed with high-fat diet

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Soy beta-Conglycinin (7S Globulin) Reduces Plasma and Liver Cholesterol in Rats Fed Hypercholesterolemic Diet

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Light microscopy and ultrastructure of the liver of Astyanax altiparanae Garutti and Britski, 2000 (Teleostei, Characidae).

Livers of thirty specimens of Astyanax altiparanae obtained from a commercial fish farm were subjected to light and transmission electron microscopy, in order to describe the hepatic parenchyma and the intrahepatic exocrine pancreatic tissue. Anatomically, the liver showed only three hepatic lobes. Histological analysis demonstrated that the hepatocytes were spread out as anastomotic cords, arranged in two cellular layers and surrounded by sinusoids. The intrahepatic exocrine pancreatic tissue exhibited an acinar arrangement and was diffused in the hepatic parenchyma. Ultrastructural analysis showed that the hepatocytes had a rounded nucleus and a rough endoplasmatic reticulum, with a parallel disposition to the nuclear membrane. The exocrine pancreatic cells showed secretion granules at the apical portion, and the rough endosplasmatic reticulum was concentrically distributed.

Healing process in anastomosis of homologous venous grafts preserved in glutaraldehyde implanted aorta of rabbits

Aim. Autologous vein (AV) is sometimes not suitable or present for a vascular restoration. Homologous vein preserved in glutaraldehyde may be an alternative to AV, but little is yet known about this graft and its healing process after implantation in arteries. The purpose of this study was to compare the initial healing process of glutaraldehyde-tanned homologous venous grafts (group 1) with fresh autologous venous grafts (group 2), at 4 or 15 days.Methods. Forty Norfolk rabbits were allocated in 2 groups of 20 animals each. The grafts was interposed in the infra-renal aorta of the rabbit. Anastomotic tensile strength (TS), hydroxyproline (HP) determination, and histology (HA) were performed.Results. TS increased in both groups, from the 4th to 15th day, (p < 0.01) in both proximal (G1: from 364.5 &PLUSMN; 98.3 g to 491.8 &PLUSMN; 107.3 g; G2: from 366.26 &PLUSMN; 85.15 g to 518.46 &PLUSMN; 82.79 g) and distal anastomosis (GI: from 363.53 &PLUSMN; 96.26 g to 507.32 &PLUSMN; 91.01 g; G2: from 352.30 &PLUSMN; 102.41 g to 528.67 &PLUSMN; 48.58 g), with no difference between the groups. HP did not change (p > 0.10) in this same period and was similar in both groups, in the proximal (GI: from 677.99 +/- 153.98 mug/100 mg to 914.92 +/- 459.83 mug/100 mg; G2: from 668.65 +/- 170.28 mug/100 mg to 669.46 +/- 319.80 mug/100 mg) as well as in the distal anastomosis (G1:from 740.07 +/- 213.53 mug/100 mg to 923.52 +/- 270.57 mug/100 mg; G2: from 737.66 +/- 266.76 mug/100 mg to 707.68 +/- 171.25 mug/100 mg). Initial inflammatory and reparative features of the anastomosis were similar in both groups.Conclusion. We can conclude that the healing process of the glutaraldehyde-tanned homologous vein graft was similar to that of the fresh autologous venous graft.