Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure.

Coffee and Caffeine Protect against Liver Injury Induced by Thioacetamide in Male Wistar Rats

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

Protective effects of Ginkgo biloba against rat liver carcinogenesis

Ginkgo biloba (EGb) has been proposed as a promising candidate for cancer chemoprevention and has shown protective effects on the liver against chemically induced oxidative injury and fibrosis. The potential beneficial effects of EGb were investigated in two rat liver carcinogenesis bioassays induced by diethylnitrosamine (DEN). In a short-term study for anti-initiating screening, male Wistar rats were fed a basal diet or supplemented diet with 500 or 1000 ppm EGb and initiated 14 days later with a single dose of DEN (100 mg/kg i.p.). The respective groups were killed 24 h or 2 weeks after DEN-initiation. Liver samples were collected for the analysis of proliferating cell nuclear antigen (PCNA), transforming growth factor alpha (TGF-alpha), p53, apoptosis and induction of single hepatocytes and minifoci positive for the enzyme glutathione S-transferase P-form (GST-P). In a medium-term study for anti-promoting screening, the animals received a single dose of DEN (200 mg/kg i.p.) and, 2 weeks later, were fed a basal diet or supplemented diet with 500 or 1000 ppm EGb for 6 weeks. All animals underwent 70% partial hepatectomy (PH) at week 3 and killed at week 8. Liver samples were colleted to analyze development of preneoplastic foci of altered hepatocytes (FAH) expressing GST-P. In the short-term study, pretreatment of rats with 1000 ppm EGb significantly reduced the rates of cell proliferation, apoptosis and p53, TGF-a immunoreactivity and the number of GST-P-positive hepatocytes. In the medium-term study, EGb treatment during the post-initiation stage failed to reduce the development of DEN-induced GST-P-positive foci. Thus, EGb presented inhibitory actions during initiation but not promotion of rat liver carcinogenesis induced by DEN. (C) 2008 Elsevier B.V. All rights reserved.

Metalloproteinases 2 and-9 activity during promotion and progression stages of rat liver carcinogenesis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Mitochondrial Alterations in Nonalcoholic Fatty Liver Disease. Pediatric Case Description of Three Submitted Sequential Biopsies

Nonalcoholic fatty liver disease (NAFLD) is a clinical-pathological syndrome that encompasses a wide spectrum of morphologic alterations, ranging from simple hepatic steatosis to a more severe stage, known as nonalcoholic steatohepatitis (NASH). The purpose of this clinical report was to contribute to the understanding of mitochondrial alterations in NAFLD. The child (13-month-old) underwent initial biopsy in the year 2000 and was diagnosed with diffuse macro and microvesicular steatosis. Two additional biopsies were performed in 2001 and 2004. A high percentage of microvesicular steatosis was observed in the biopsies performed in 2000 and 2001. Mitochondrial size was slightly increased in the biopsy performed in the year 2000, significantly increased in 2001 and decreased in 2004. The presence of "mitochondrial hypertrophy" in the hepatocytes of an asymptomatic pediatric patient whose disease presentation was typical of NAFLD, excluding other pathological processes, allowed us to suspect that such a defect was considered the primary mitochondrial disorder.

Absence of chemopreventive influence of propolis on the rat liver altered foci development

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

An acqueous extract of Bidens pilosa L. protects liver from cholestatic disease: experimental study in young rats

OBJETIVO: Testar o efeito hepatoprotetor do extrato aquoso de Bidens pilosa L. (EBP) na doença hepática induzida pela ligadura e ressecção do ducto biliar comum (LRDBC) em ratos jovens. MÉTODOS: Estudamos ratos Wistar com 21º. dia de vida (P21) divididos em quatro grupos de 10 animais, Grupo SA: operação simulada e água; Grupo SD: operação simulada e EBP (160mg de folhas frescas/100g de peso corporal/dia); Grupo LA: LRDBC e água e Grupo LD: LRDBC e EBP diariamente. O tempo de sono por pentobarbital (TSP), aspartato (AST) e alanina (ALT) aminotransferase foram determinadas após o sacrifício (P70). O Score de Ruwart (SR) para fibrose hepática foi atribuído para cada animal. Foi realizada análise de variância com dois fatores e pelo teste de Tukey para comparações múltiplas ou por teste não paramétrico. RESULTADOS: Houve diferença estatisticamente significativa entre LA e LD nas variáveis: TSP (médias LA=390; LD=173), AST (médias LA=8, LD=5), ALT (medianas LA=2; LD=1) e SR (medianas LA=2; LD=1). CONCLUSÃO: EBP poderá ser empregado na fitoterapia da doença hepática induzida pela colestase obstrutiva crônica, pois protege a função hepática, diminui a velocidade de necrose e a intensidade da fibrose hepática na obstrução biliar extra-hepática.

Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected synchronously or metachronously in patients with GISTs may represent histogenetically distinct lesions and should be sampled to confirm or exclude metastatic GISTs. (C) 2008 WJG. All rights reserved.

Sequencing and expression analysis of hepcidin mRNA in donkey (Equus asinus) liver

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

Lipopolysaccharide infusion up-regulates hepcidin mRNA expression in equine liver

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

Mycobacterium DNA detection in liver and skin of a horse with generalized sarcoidosis

Sarcoidosis is a rare equine skin disease characterized primarily by an exfoliative and granulomatous dermatitis but also presenting granulomatous inflammation of multiple systems. The current report presents the clinical and histopathological findings of sarcoidosis in a 16-year-old American Quarter Horse gelding with nested polymerase chain reaction Mycobacterium spp. DNA detection within hepatic and skin samples. Mycobacterium spp. may play a role in the pathogenesis of equine sarcoidosis as has been proposed for human sarcoidosis.

Aplicações clínicas da suplementação de L-carnitina

A carnitina, uma amina quaternária (3-hidroxi-4-N-trimetilamino-butirato), é sintetizada no organismo (fígado, rins e cérebro) a partir de dois aminoácidos essenciais: lisina e metionina, exigindo para sua síntese a presença de ferro, ácido ascórbico, niacina e vitamina B6. Tem função fundamental na geração de energia pela célula, pois age nas reações transferidoras de ácidos graxos livres do citosol para mitocôndrias, facilitando sua oxidação e geração de adenosina Trifosfato. A concentração orgânica de carnitina é resultado de processos metabólicos - como ingestão, biossíntese, transporte dentro e fora dos tecidos e excreção - que, quando alterados em função de diversas doenças, levam a um estado carencial de carnitina com prejuízos relacionados ao metabolismo de lipídeos. A suplementação de L-carnitina pode aumentar o fluxo sangüíneo aos músculos devido também ao seu efeito vasodilatador e antioxidante, reduzindo algumas complicações de doenças isquêmicas, como a doença arterial coronariana, e as conseqüências da neuropatia diabética. Por esse motivo, o objetivo do presente trabalho foi descrever possíveis benefícios da suplementação de carnitina nos indivíduos com necessidades especiais e susceptíveis a carências de carnitina, como os portadores de doenças renais, neuropatia diabética, síndrome da imunodefeciência adquirida e doenças cardiovasculares.