Fipronil na bioenergética de mitocôndrias isoladas de figado de rato

Pós-graduação em Ciência Animal - FMVA

Chemoprevention of preneoplastic liver foci development by dietary mushroom Agaricus blazei Murrill in the rat

The chemopreventive potential of an Agaricus blazei (Ab) Murrill mushroom meal was investigated in a medium-term rat liver carcinogenesis assay. Male Wistar rats initiated for hepatocarcinogenesis with diethylnitrosamine (DEN, 200 mg/kg i.p.) were fed during a 6-week period with the dry powdered mushroom strains Ab 29 or 26, each one with opened (OB) or closed basidiocarp (CB), mixed at 10% level in a basal diet. All experimental animals and controls were subjected to partial hepatectomy at week 3 and killed at week 8. Chemopreventive activity of the mushroom meal was observed for the Ab 29 (OB and CB) and Ab 26 (CB) strains in terms of the number of putative preneoplastic altered foci of hepatocytes which express either the enzyme glutathione S-transferase, placental form (GST-P+) or the transforming growth factor-alpha, and for the Ab 29 (OB) and Ab 26 (CB) strains on the size of GST-P-divided by foci. This was associated with inhibition of foci cell proliferation in the animals fed the Ab 29 (013) and Ab 26 (CB) strains. The results suggest that the protective influence of the Ab meal against the DEN potential for rat liver carcinogenicity depends on both the strain and period of mushroom harvest. (C) 2003 Elsevier Ltd. All rights reserved.

Effects of swim training on liver carcinogenesis in male Wistar rats fed a low-fat or high-fat diet

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

Effects of fasting and intermittent fasting on rat hepatocarcinogenesis induced by diethylnitrosamine

The influences of fasting on DEN-initiation and of intermittent fasting (IF) on the rat liver chemical carcinogenesis process were evaluated in a 52-week long assay. Three groups of adult male Wistar rats were used: Groups I to 3 were treated with a single i.p. injection of 200 mg/kg of diethylnitrosamine (DEN). Group 2 was submitted to 48 h fasting prior to DEN treatment. After the 4th week, Group 3 was submitted to IF, established as 48 h weekly fasting during 48 weeks, while Groups I and 2 were fed ad libitum until the 52nd week. All animals were submitted to 70% partial hepatectomy and sacrificed at the 3rd and 52nd weeks, respectively. Fasting prior to DEN-initiation did not influence the development of altered foci of hepatocytes (AFHs) and of hepatic nodules (Group 2 vs. Group G1). IF inhibited the development of preneoplastic lesions, since this dietary regimen decreased the number and the size of glutathione S-transferase (GST-P) positive foci and the number and size of liver nodules (Group G3 vs. Group G1), the inhibitory effect of IF was also reflected in the development of clear and basophilic cell foci. These results indicate that long-term IF regimen exerts an anti-promoting effect on rat hepatocarcinogenesis induced by DEN. (C) 2002 Wiley-Liss, Inc.

Agaricus blazei (Himematsutake) does not alter the development of rat diethylnitrosamine-initiated hepatic preneoplastic foci

The modifying potential of crude extracts of the mushroom Agaricus blazei Murrill (Himematsutake) on the development and growth of glutathione S-transferase placental form (GST-P)-positive liver foci (liver preneoplastic lesion) was investigated in adult male Wistar rats. Six groups of animals were used. Groups 2 to 5 were given a single i.p. injection of 200 mg/kg b.w. of diethylnitrosamine (DEN) and groups 1 and 6 were treated with saline at the beginning of the experiment. After 2 weeks, animals of groups 3 to 6 were orally treated with three dose levels of aqueous extracts of the mushroom A. blazei (1.2, 5.6, 11.5, and 11.5 mg/ml of dry weight of solids) for 6 weeks. All animals were subjected to two-thirds partial hepatectomy at week 3 and sacrificed at week 8. Two hours before sacrifice, ten animals of each group were administered a single i.p injection of 100 mg/kg of bromodeoxyuridine (BrdU). Apoptotic bodies and BrdU-positive hepatocyte nuclei were quantified in liver sections stained for hematoxylin and eosin (H&E) (eosinophilic foci) and simultaneously stained for GST-P expression (GST-P-positive foci), respectively. The 6-week treatment with A. blazei did not alter the development (number and size) of GST-P-positive foci and did not affect the growth kinetics of liver normal parenchyma or foci in DEN-initiated animals. Our results indicate that the treatment with aqueous extracts of the mushroom A. blazei during the post-initiation stage of rat liver carcinogenesis does not exert any protective effect against the development of GST-P-positive foci induced by DEN. (Cancer Sci 2003; 94: 188-192).

Liver dysfunction in patients bitten by Crotalus durissus terrificus (Laurenti, 1768) snakes in Botucatu (State of São Paulo, Brazil)

Os autores estudaram 32 doentes picados por serpentes venenosas, sendo 16 picados por Bothrops spp. e 16 por Crotalus durissus terrificus. Trinta doentes eram do sexo masculino e dois do feminino com idades variando entre 8 e 63 anos (méda 33±15). A prova da retenção da bromosulfaleína apresentou-se aumentada na maioria dos doentes picados por serpentes Crotalus durissus terrificus. Houve correlação positiva entre a retenção da bromosulfaleína e os níveis séricos de alanina aminotransferase e entre alanina e aspartato aminotransferase apenas nos doentes do grupo Crotalus. Um dos doentes evoluiu para o óbito e apresentou no exame anatomopatológico do fígado degeneração hidrópica e lesões mitocondriais. Os autores concluem que as alterações hepáticas são causadas por pelo menos dois mecanismos a saber: lesão mitocondrial por efeito do veneno crotálico; efeito das citoquinas, especialmente a interleucina-6.

Effect of organic synthetic food colours on mitochondrial respiration

Eleven organic synthetic dyes, currently or formerly used as food colours in Brazil, were tested to determine their effect on mitochondrial respiration in mitochondria isolated from rat liver and kidney. The compounds tested were: Erythrosine, Ponceau 4R, Allura Red, Sunset yellow, Tartrazine, Amaranth, Brilliant Blue, Indigotine Blue, Fast Red E, Orange GGN and Scarlet GN. All food colours tested inhibited mitochondrial respiration (State III respiration, uncoupled) supported either by α-ketoglutarate or succinate. this inhibition varied largely, e.g. from 100% to 16% for Erythrosine and Tartrazine respectively, at a concentration of 0.1 mg food colour per mitochondrial protein. Both rat liver and kidney mitochondria showed similar patterns of inhibition among the food colours tested. This effect was dose related and the concentration to give 50% inhibition was determined for some of the dyes. The xanthene dye Erythrosine, which showed the strongest effect, was selected for further investigation on mitochondria in vivo.

Efeitos da abamectina na bioenergética de mitocôndrias isoladas de fígado de rato: Juliana Carla Castanha Zanoli. -

Pós-graduação em Ciência Animal - FMVA

Mecanismos de toxicidade dos metabólitos do fipronil, dessulfinil e sulfona, em mitocôndrias isoladas de fígado de rato

Pós-graduação em Ciência e Tecnologia Animal - FEIS

Promotion of hepatocarcinogenesis by hexachlorobenzene in energy-restricted rats

The interaction between dietary energy restriction and low dose of the fungicide hexachlorobenzene (HCB) was evaluated in a rat liver medium-term bioassay for carcinogenesis. Male Wistar rats were fed a control or a 50% energy-restricted diet, both added or not with 50 ppm HCB, for 6 weeks. HCB exposure or energy restriction separately did not exert any influence on the development of glutathione S-transferase placental form (GST-P+) foci of hepatocytes. Simultaneous HCB exposure and energy restriction induced a significant increase in liver centrilobular hypertrophy and GST-P+ foci development. Our findings suggest that energy restriction increases liver response to low dose of HCB, unmasking the promoting potential of this fungicide. (C) 2000 Elsevier B.V. Ireland Ltd. All rights reserved.

Cocaine mutagenicity and hepatocarcinogenicity evaluations in rodents

The mutagenicity (clastogenicity) and the carcinogenicity (promoting potential) of cocaine were evaluated, respectively, by the mouse bone marrow micronucleus test (study I) and by the initiated rat liver bioassay (study II). In study I, two administration routes (i.p. and i.v.) and two sampling times (24 and 48 hours) after cocaine treatment were studied. Swiss male mice were treated with cocaine at doses of 0, 18, 37, and 75 mg/kg and 0, 2, 4, and 8 mg/kg by i.p. and i.v. routes, respectively. No significant differences were observed between treated and negative control groups regarding the frequencies of micronuclei and the polichromatic/normochromatic erythrocyte (PCE/NCE) ratios. In study II, the development of putative preneoplastic foci of hepatocytes expressing the enzyme glutathione S-transferase placental form (GST-P+) was utilized as the end-point marker in a 8-week rat liver bioassay. The animals were initiated for carcinogenesis by a single i.p. sub-carcinogenic dose of diethylnitrosamine (DEN). After a 6-week exposure to 5 or 10 mg/kg of cocaine i.v. twice a week there was no enhancement of GST-P+ foci development above the values of the control DEN-only treated animals. Also, cocaine did not induce any toxicity as evidenced by the absence of alterations of rat body and liver weights and of liver biochemical function and morphology. The results suggest that cocaine does not have a mutagenic effect on the mouse bone marrow cells or promoting activity on the rat hepatocarcinogenesis process. Teratogenesis Carcinog. Mutagen. 18:199-208, 1998. (C) 1998 Wiley-Liss, Inc.

Steatosis of indeterminate cause in a pediatric group: is it a primary mitochondrial hepatopathy?

CONTEXTO E OBJETIVO: em crianças, a esteatose hepática pode se relacionar a erros inatos do metabolismo (EIMs) ou à doença hepática gordurosa não-alcoólica (DHGNA). O objetivo deste estudo foi avaliar e caracterizar esteatose de causa indeterminada por meio de análises morfológica e morfométrica em tecido hepático. TIPO DE ESTUDO E LOCAL: Estudo transversal nos Departamentos de Patologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas (FCM-Unicamp) e Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (FMB-Unesp). MÉTODOS: Foram utilizadas 18 biópsias hepáticas consecutivas obtidas de 16 pacientes com idade variando de 3 meses a 12 anos e 9 meses, inseridas num banco de dados no período do estudo, que foram analisadas por microscopia óptica e eletrônica. Na microscopia eletrônica, foi realizada determinação da densidade mitocondrial e da área superficial média das mitocôndrias nos hepatócitos. Dez pacientes com idade variando de 1 a 14 anos foram usados como grupo controle. RESULTADOS: Foi detectada esteatose pura, não acompanhada por fibrose ou outra alteração histológica. Foi verificado que, na predominância de esteatose microvesicular, houve aumento significativo da área mitocondrial média. CONCLUSÃO: A esteatose microvesicular pode estar relacionada à hepatopatia mitocondrial primária, principalmente devido à redução na β-oxidação ou parcial estagnação da fosforilação oxidativa. Por essas razões, esta forma de esteatose (que não pode ser chamada de pura) possivelmente represente uma fase inicial no amplo espectro da DHGNA. Chamamos a atenção para casos de esteatose no grupo pediátrico com predomínio da forma microvesicular, uma vez que pode haver associação com desordens mitocondriais.

Mecanismos da intoxicação do fígado de rato causada pelo gossipol

O fígado desempenha uma função central no metabolismo devido à sua interposição entre o trato digestivo e a circulação geral do organismo. Ele é também o principal órgão envolvido na biotransformação de substâncias exógenas (xenobióticos), com capacidade de converter compostos hidrofóbicos em hidrossolúveis, mais facilmente eliminados pelo organismo. O gossipol é uma substância fenólica tóxica presente na semente de algodão (Gossypium sp). Com o objetivo de estudar os mecanismos envolvidos na hepatotoxicidade do gossipol avaliou-se os seus efeitos no sistema antioxidante do fígado de ratos no que diz respeito ao estresse oxidativo e aspectos histopatológicos. Foram utilizados ratos machos da linhagem Wistar, separados em dois grupos, sendo que um recebeu óleo de canola (veículo, grupo Controle) e o outro recebeu gossipol na dosagem de 40 mg/kg de peso vivo do animal por 15 dias (grupo Tratado). O tratamento com gossipol promoveu alterações na atividade sérica das enzimas marcadoras de dano hepático e um significativo estresse oxidativo caracterizado pela diminuição nos níveis da glutationa reduzida (GSH) e consequente aumento da glutationa oxidada (GSSG), incluindo, ainda, danos à membrana plasmática e de organelas demonstrados pela peroxidação lipídica. O resultado da avaliação histopatológica demonstrou degeneração dos hepatócitos.

Efeitos do treinamento aeróbio na hepatocarcinogênese química em ratos Wistar alimentados com dieta basal ou hiperlipídica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Hepatoprotective Effect of Arctium lappa Root Extract on Cadmium Toxicity in Adult Wistar Rats

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