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).

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.

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.

Influence of aqueous extract of Agaricus blazei on rat liver toxicity induced by different doses of diethylnitrosamine

The modifying potential of prior administration of an aqueous extract of the mushroom Agaricus blazei Murrill (Agaricaceae) (Ab) on hepatotoxicity induced by different doses of diethylnitrosamine (DEN) in male Wistar rats was evaluated. During 2 weeks, animals of groups G3 (Ab+DEN50), G5 (Ab+DEN100), G7 (Ab+DEN200), and G8 (Ab-treated) were treated with the A. blazei through drinking water. After this period, groups G2 (DEN50), G3 (Ab+DEN50), G4 (DEN100) G5 (Ab+DEN100), G6 (DEN200), and G7 (Ab+DEN200) were given a single i.p. injection of 50, 100 and 200 mg/kg of DEN, respectively, while groups G1 (nontreated) and G8 (Ab-treated) were treated with 0.9% NaCl only. All animals were killed 48 h after DEN or NaCl treatments. The hepatocyte replication rate was estimated by the index of the proliferating cell nuclear antigen (PCNA) positive hepatocytes and the appearance of putative preneoplastic hepatocytes through expression of the enzyme glutathione S-transferase placental form (GSTP). After DEN-treatment, ALT levels, PCNA labeling index, and the number of GST-P positive hepatocytes were lower in rats that received A. blazei treatment and were exposed to 100 mg/kg of DEN. Our findings suggest that previous treatment with A. blazei exerts a hepatoprotective effect on both liver toxicity and hepatocarcinogenesis process induced by a moderately toxic dose of DEN. (C) 2002 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.

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)

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

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

Fructose in fetal cord blood and its relationship with maternal and 48-hour-newborn blood concentrations

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

Período de absorção intestinal de macromoléculas em cabritos recém-nascidos após a ingestão de colostro bovino

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

Fruit and seed ontogeny related to the seed behaviour of two tropical species of Caesalpinia (Leguminosae)

Caesalpinia echinata and C ferrea var. ferrea have different seed behaviours and seed and fruit types. Comparison of the seed ontogeny and anatomy partly explained the differences in seed behaviour between these two species of Brazilian legumes; some differences were also related to fruit development. The seed coat in C. ferrea consisted of two layers of osteosclereids, as well as macrosclereids and fibres, to form a typical legume seed coat, whereas C. echinata had only macrosclereids and fibres. In C. echinata, the developing seed coat had paracytic stomata, a feature rarely found in legume seeds. These seed coat features may account for the low longevity of C. echinata seeds. The embryogeny was similar in both species, with no differences in the relationship between embryo growth and seed growth. The seeds of both species behaved as typical endospermic seeds, despite their different morphological classification (exendospermic orthodox seeds were described for C. echinata and endospermic orthodox seeds for C. ferrea). Embryo growth in C. ferrea accelerated when the sclerenchyma of the pericarp was developing, whereas embryonic growth in C. echinata was associated with the conclusion of spine and secretory reservoir development in the pericarp. Other features observed included an endothelial layer that secreted mucilage in both species, a nucellar summit, which grew up into the micropyle, and a placental obturator that connected the ovarian tissue to the ovule in C. ferrea. (C) 2004 the Linnean Society of London.

Somatic cell nuclear transfer is associated with altered expression of angiogenic factor systems in bovine placentomes at term

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

Sibutramine Effects on the Reproductive Performance of Pregnant Overweight and Non-Overweight rats

It is well established that sibutramine produces weight loss and is used frequently in women of childbearing age. However, the potential adverse consequences attributed to sibutramine use by women who may become pregnant is not known. It was thus of interest to determine the effects of sibutramine on the reproductive performance of pregnant rats. Overweight as well as non-overweight female Wistar rats were treated with sibutramine (6 mg/kg) orally, daily for 15 d and then mated with normal male rats. Pregnancy was confirmed and treatment continued with sibutramine until d 14 of pregnancy. on d 20 of pregnancy all rats were anesthetized for determination of various maternal and fetal parameters. There was a significant maternal weight reduction at the end of pregnancy in the non-overweight drug-treated group compared to the control (non-overweight, no drug). Sibutramine alone and overweight condition alone produced a significant increase in postimplantation loss and placental index. In the overweight with or without sibutramine groups a significant decrease in fetal weight was noted. Data suggest that sibutramine alone or the condition of excess weight in the absence of drugs produced impaired reproductive performance. However, treatment of overweight rats with sibutramine did not further exacerbate fetal loss compared to sibutramine alone or the effects noted with excess weight alone.

Effects of Gestational and Lactational Fenvalerate Exposure on Immune and Reproductive Systems of Male Rats

The aim of this study was to determine the consequent reproductive developmental and immunotoxic effects due to exposure to fenvalerate during pregnancy and lactation in male offspring of maternal-treated rats. Pregnant rats were treated daily by oral gavage with 40 or 80 mg/kg of fenvalerate or corn oil (vehicle, control), from d 12 of pregnancy to d 21 of lactation. Immune and reproductive developmental effects were assessed in male offspring at postnatal days (PND) 40 (peripuberty), 60 (postpuberty), and 90 (sexual maturity). Treatment with the higher dose (80 mg/kg) resulted in convulsive behavior, hyperexcitability, and mortality in 45% of the dams. Fenvalerate was detected in the fetus due to placental transfer, as well as in pups due to breast-milk ingestion, persisting in male offspring until PND 40 even though pesticide treatment was terminated on PND 20. However, fenvalerate did not produce marked alterations in age of testicular descent to the scrotum and prepucial separation, parameters indicative of puberty initiation. In contrast, at puberty, there was a reduction in testicular weight and sperm production in male offspring of maternal-treated rats. At adulthood, the sperm counts and fertility did not differ between control and treated groups. Testosterone levels were not changed at any time during reproductive development. Similarly, no apparent exposure-related effects were detected in the histological structures of the lymphohematopoietic system. Data indicate that fenvalerate, in this experimental model, interfered with initial development of the male reproductive system, but that these effects on sperm production or fertility did not persist into adulthood. There was no apparent evidence that fenvalerate altered testosterone levels or produced a disruption in male endocrine functions.

Maternal undernutrition and the offspring kidney: from fetal to adult life

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

Metabolic, ventilatory, and hygric physiology of a South American marsupial, the long-furred woolly mouse opossum

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)