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Chemical pollutants include the harmful effects of various substances on soils, water bodies, and biodiversity. Amphibians are one of the most endangered groups of vertebrates and are impacted by chemical pollutants in various ways due to their complex life cycles. Since trace pollutant concentrations vary across environments, different frog ecomorphs (classified by their microhabitat use) may have different exposures. We aimed to determine the association between frog ecomorphs and the occurrence of histopathological hepatic lesions (HHLs) as an indicator of contaminant exposure. We focused on small forest streams near a large urban region in Brazil, heavily polluted in the 1980s. We examined 104 frog specimens from various families. All specimens exhibited HHLs, with melanomacrophages being the most common (n = 99). Arboreal frogs exhibited more vascular congestion, while terrestrial frogs showed structural hepatic damage. Higher cobalt levels were linked to increased liver necrosis in arboreal frogs and structural issues in both arboreal and terrestrial frogs. Cadmium was associated with hepatitis in terrestrial frogs. Although metal levels had no significant effects on rheophilic frogs, the prevalence of hepatitis and necrosis indicated complex exposure pathways. Iron and aluminum were linked to fewer lesions in rheophilic frogs, suggesting resilience. The high prevalence of HHLs signals an ongoing issue, with variations among ecomorphs suggesting differential exposure to pollutants and posing a complex challenge for community conservation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Roundup Transorb ® (RDT) is the most popular glyphosate-based herbicide (GHB) used in agriculture, and its impact extends to non-target organisms. The annual killifish Austrolebias charrua is an endangered species endemic to southern South America and inhabits temporary ponds. This study evaluates the effects of RDT concentrations (0.065 and 5 mg/L GAE) on A. charrua exposed for 96 h. Gene expression of cat, sod2, gstα, gclc, and ucp1 was evaluated on the liver and gills. Highlighting that even at low concentrations permitted by Brazilian legislation, the RDT can have adverse effects on A. charrua., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The accidental spill of petroleum asphalt cement (PAC) in São Raimundo (SR Harbor, located on the Rio Negro (Manaus, Amazonas, Brazil) was monitored through the analysis of polyciclic aromatic hydrocarbons (PAHs) in water and a set of biomarkers in fishes (exposure biomarkes: PAHs-type metabolites concentrations in bile; the activities of ethoxyresorufin-O-deethylase (EROD), glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in liver. Effect biomarkers: lipid peroxidation concentration (LPO) in liver, acetylcholinesterase activity in brain, and genotoxic DNA damage in erythrocytes). Two fish species, Acarichthys heckelii and Satanoperca jurupari, were collected 10, 45, and 90 days after the PAC spill in São Raimundo. At the same time, fish were collected from the Tupé Sustainable Development Reserve (Tupé) which served as a reference area. The sampling periods were related to the rising waters of the natural flood pulse of the Rio Negro. Higher concentrations of PAHs in water were observed at 10 and 45 days and returned to the values of TP 90 days after the PAC spill, a period in which harbor waters rose about 0.2 m. Unlike the PAHs in water, biomarker responses in both fish species significantly increased following the PAC spill in SR. Hepatic ethoxyresorufin-O-deethylase (EROD), PAH-like metabolites in bile, and erythrocyte DNA damage increases, together with inhibition of acetylcholinesterase (AChE) activity in the brain were the most evident responses for both fish species. The calculated pyrolytic index showed mixed sources of PAHs (petrogenic and pyrolytic). The applied PCA-FA indicated important relationships between dissolved organic carbon (DOC) and PAHs concentrations in water, where DOC and PAHs concentrations contributed to biomarkers responses for both fish species in all collection periods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Adalberto Luis Val reports financial support was provided by Foundation for Research Support of Amazonas State. Adalberto Luis Val reports financial support was provided by Coordination of Higher Education Personnel Improvement. Vera Maria Fonseca de Almeida-Val reports was provided by Foundation for Research Support of Amazonas State. Vera Maria Fonseca de Almeida-Val reports financial support was provided by Coordination of Higher Education Personnel Improvement. Adalberto Luis Val reports financial support was provided by National Council for Scientific and Technological Development. Vera Maria Fonseca de Almeida e Val reports financial support was provided by National Council for Scientific and Technological Development. Helen Sadauskas-Henrique reports financial support was provided by National Council for Scientific and Technological Development. Derek Felipe Campos reports was provided by National Council for Scientific and Technological Development. Susana Braz-Mota reports financial support was provided by National Council for Scientific and Technological Development. Daiani Kochhann reports financial support was provided by National Council for Scientific and Technological Development., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The most recent dam rupture in Brazil released tons of mining tailings into the upper course of the Paraopeba River, affecting this river in an unprecedented way. The present study aimed to evaluate the influence of heavy metals on Prochilodus costatus, an important commercial species in Brazil, four years after the dam colapse. To this end, biomarkers of heavy metals, oxidative stress, and environmental stress were analyzed, and histological analyses of target organs were performed. The results demonstrated critical contamination of fish from the Paraopeba River. Increased expression of Metallothioneins - MTs, Heat Shock Protein - HSP70, and inducible nitric oxide synthase - iNOS, as well as greater rates of histological changes in the liver, spleen, and gonads, were observed in P. costatus. These findings demonstrate that, despite past contamination, the metals present in mining tailings have significantly increased the contamination of the Paraopeba River basin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is evidence that propolis exhibits anti-inflammatory, anticancer, and antioxidant properties. We assessed the potential beneficial effects of Brazilian propolis on liver injury in nonalcoholic fatty liver disease (NAFLD). Our findings demonstrate that Brazilian propolis suppresses inflammation and fibrosis in the liver of mice with NAFLD by inhibiting the expression of genes involved in endoplasmic reticulum (ER) stress. Additionally, Brazilian propolis also suppressed the expression of ER stress-related genes in HepG2 cells treated with an excess of free fatty acids, leading to cell apoptosis. A deeper analysis revealed that kaempferol, one of the components present in Brazilian propolis, induces cell proliferation through the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and protects against oxidative stress. In conclusion, Brazilian propolis exhibits hepatoprotective properties against oxidative stress by inhibiting ER stress in NAFLD-induced model mice.

Urban sewage is a source of major contamination in aquatic systems and contributes to environmental and human health disturbances. This study investigates the effects of sewage-polluted waters from Iguaçu River on the health of juvenile Oreochromis niloticus. Two hundred four specimens were exposed to riverine water in four groups: no diluted, 25 and 50 % diluted water and a control group without tested water for 72 days. Biological samples were obtained for histopathological, neurotoxicity, antioxidant defenses, genotoxicity, metallothionines expression and polycyclic aromatic hydrocarbons (PAHs) metabolites. The results showed histopathological alterations in liver and gills, genotoxic alteration in erythrocytes, reduction of acetylcholinesterase activity in brain and muscle, activation of antioxidant defenses in the liver, recruitment of metals by metallothionein and the detection of PAHs metabolites in bile. These results demonstrate that juveniles of O. niloticus are susceptible to Iguaçu River exposure water and they can be used as indicator of water quality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Aloysia polystachya (Griseb) Moldenke (Verbenaceae), popularly known as "burrito", is a South American species widely prescribed by local Brazilian healers for the treatment of cardiovascular diseases. However, its antihypertensive and cardioprotective effects are still unknown., Aim: To evaluate the role of the ethanol-soluble fraction of A. polystachya leaves (ESAP) against hypertension in spontaneously hypertensive rats (SHRs), as well as its safety, morphoanatomical and phytochemical aspects., Materials and Methods: First, the leaves and stems of A. polystachya were analyzed by optical and scanning electron microscopy in order to provide anatomical data for quality control. Then, ESAP was obtained and its chemical profile was analyzed by LC-DAD-MS. In addition, the cytotoxic and acute toxicity potential of ESAP were evaluated in six cell lines and in female Wistar rats, respectively. Next, female spontaneously hypertensive rats (SHRs) received ESAP (30, 100, 300 mg/kg), hydrochlorothiazide (25 mg/kg), or vehicle once daily for 28 days. Weekly kidney function was monitored by analyzing urinary parameters. At the end of the 28-day treatment, the electrocardiographic profile, blood pressure, and renal and mesenteric vascular reactivity were evaluated. Relative organ (heart, kidney, and liver) weights and biochemical parameters were also evaluated. Finally, the heart, kidneys, and aorta were collected for determination of the tissue redox state, cardiac morphometry, and histopathological analysis., Results: The chemical profile of ESAP was composed by organic acids, a nucleoside, methoxylated flavones and glycosylated compounds including phenolic acids, phenylpropanoids, iridoids and monoterpenes. No signs of toxicity were observed in all cell's lines nor in female Wistar rats submitted to this trial. All SHRs from the negative control group presented a reduction in renal function, alterations in the renal and mesenteric vascular reactivity, and electrocardiographic and morphometric changes typical of ventricular hypertrophy. Oral prolonged ESAP-administration in SHRs was able to reverse renal, electrocardiographic and hemodynamic changes induced by hypertension. Moreover, ESAP-treatment was able to modulate the vascular and renal arterial reactivity and tissue redox state. The aforementioned data were accompanied by reduction of cardiac hypertrophy., Conclusion: In this study, we present important anatomical and phytochemical data that contributed to the correct identification and quality control of A. polystachya. In addition, we have shown that ESAP is safe after acute administration and present significant cardioprotective effects (at 30, 100, and 300 mg/kg doses) in SHRs after prolonged treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The wastewater contamination of urban rivers is a concern for biodiversity and a consequence from poor urban conservation policies. In the current study, the impact of urban and industrial activities was investigated in Iguaçu river (Southern Brazil) using juvenile Oreochromis niloticus, after trophic and chronic exposure (25, 50 and 100 %), over 81 days. After exposure liver, gills, gonads, brain, muscle, and blood were sampled for chemical, biochemical, histopathological, genotoxic and molecular analyses. Water levels of persistent organic pollutants such as polychlorinated biphenyls, organochlorine pesticides, polycyclic aromatics hydrocarbon (PAHs) and metals were investigated. The redox unbalance, histopathological and increase in vitellogenin expression in fish revealed both the bioavailability of micropollutants and their harmful effects. According to the results, the level of Iguaçu river pollution negatively impacts the health of O. niloticus revealing and highlighting the risk of this pollution exposure to biota and human populations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Brazilian flora is rich in plants with medicinal properties, which though popular, has contributed to the development of a range of phytotherapic products that use plants to treat and cure diseases. However, studies that use Brazilian plants in the treatment of metabolic disorders are still scarce in the literature., Objective: The aim of this study was to analyze the effect of hepatotoxicity Lafoensia pacari on the metabolism of mice with obesity induced by a high-fat diet and to verify the phytochemical difference between the Lafoensia pacari bark of the trunk, leaves, and branches., Methods: The plant material was collected from April to May in the municipality of Bonito de Minas, MG, Brazil. Qualitative tests for the presence of secondary metabolite classes were performed for leaves, branches and bark of the trunk. Through histological analysis, we evaluated hepatocytes and cell lesions in the liver., Results: The comparative phytochemical analysis of the plant did not reveal alterations between the different plant parts. The phytochemical test showed that is preferable to use the leaves to make the extract to be applied, aiming to reduce the plant aggression. After treatment, greater changes were observed in the animals that received the high-fat diet and the hydroethanolic extract; the levels of AST, ALT, albumin and creatinine that were increased, thus demonstrating a possible toxicity. There were no significant differences in body weight. In the histological analysis, the animals without plant treatment displayed decreased liver weight and reduction in the inflammatory infiltrate., Conclusion: We conclude that Lafoensia pacari should be better evaluated for oral consumption and may cause liver damage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ethnopharmacological Relevance: Passiflora edulis f. flavicarpa O. Deg. is a native Brazilian fruit known as sour or yellow passion fruit. From its peel, mainly in the northeast of Brazil, is produced a flour that is largely used as folk medicine to treat diabetes and other metabolic conditions., Aim of the Study: The aim of the study was to show the effects of P. edulis peel flour (PEPF) in metabolic disorders caused by cafeteria diet in mice., Material and Methods: The antioxidant activity in vitro of PEPF extract was determined by ferric reducing/antioxidant power, β-carotene/linoleic acid system and nitric oxide scavenging activity assay. C57BL/6 mice divided in 3 groups: Control group, fed on a standard diet (AIN); Cafeteria diet (CAF) group, fed on a cafeteria diet, and PEPF group, fed on a cafeteria diet containing 15% of PEPF, during 16 weeks. The glucose tolerance and insulin sensitivity were evaluated through the glucose tolerance test (GTT) and the insulin tolerance test (ITT). After the intervention period, blood, hepatic, pancreatic and adipose tissues were collected for biochemical and histological analysis. Cholesterol, triglyceride, interleukins and antioxidant enzymes were measured in the liver tissue., Results: PEPF extract presented antioxidant activity in the higher concentrations in the performed assays. The PEPF intake decreased the body weight gain, fat deposition, predominantly in the liver, improved the glucose tolerance and insulin sensitivity in metabolic changes caused by cafeteria diet., Conclusion: Together, the data herein obtained points out that P. edulis peel flour supplementation in metabolic syndrome condition induced by CAF-diet, prevents insulin and glucose resistance, hepatic steatosis and adiposity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Plastic waste disposal in the environment is a major issue worldwide, whose effects on different biotas are the object of several investigations. The toxicity caused by microplastics (MPs) in organisms living in freshwater environments remains little explored. Little is known about the consequences of the exposure to these pollutants on the health of amphibians. Thus, we tested the hypothesis that the exposure of Physalaemus cuvieri tadpoles to microplastic polyethylene (PE MP) causes histopathological damage to their liver. Data collected after seven days of exposure to MPs (60 mg/L) have shown that pollutant bioaccumulation in tadpoles' liver was correlated to different histopathological changes (blood vessel dilation, infiltration, congestion, hydropic degeneration, hypertrophy and hyperplasia), which showed the histopathotoxicity of MPs. Furthermore, we observed changes in hepatocyte nuclei size (area and diameter), volume and shape induced by the exposure to PE MPs, a fact that evidenced the cytotoxic effect of these pollutants. To the best of our knowledge, the current study is the first to report the histopathotoxicity of PE MPs in representatives of the amphibian group, and it contributes to improving knowledge about these pollutants and how they may affect the health of these animals., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Environmental disasters such as the rupturing of mine tailings dams are a major concern worldwide. In the present study, we assess the effects of the release of mine waste due to the rupture of the Fundão dam on two native fish species (Hoplias intermedius and Hypostomus affinis) from the Doce River basin. Two sampling sites were chosen: S1, a reference site, and S2, contaminated by mining waste. Water and sediment were collected to evaluate metals concentration. Adult fish were caught to analyse biological parameters, hepatic histopathology, and biomarkers of metal contamination. Compared to site S1, the concentration of manganese was statistically higher in water while lead, nickel, and arsenic were statistically higher in the sediment from site S2, and iron had no significant difference between sites. At site S1, fish of both species presented hepatic tissue with normal architecture. At site S2, hepatic alterations, such as cytoplasmic vacuolization and necrosis were frequently found in both species. Regarding the histopathological index, higher values were found in both species from site S2. The positive antibody reactions for cytochrome P450 1A (CYP1A) and metallothionein (MT) were statistically greater in site S2 for both species. The oxidative stress biomarkers, superoxide dismutase (SOD) and catalase (CAT) were statistically higher in H. intermedius from site S2, but only CAT was statistically greater in H. affinis at site S2. These results demonstrate that the release of mineral residues from the rupture of the Samarco mine dam is provoking hepatic damage in the fish from the Doce River besides inducing the expression of proteins and enzymes related to metal contamination., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The purpose of this study was to identify the long-term effect of chemical exposure on the liver. Laboratory tests included alanine aminotransferase (ALT) dosage and oxidative stress tests, such as thiobarbituric acid reactive substances in plasma and superoxide dismutase (SOD) and glutathione S-transferase analysis in erythrocytes. The cross-sectional study comprised 70 workers, 30 of them exposed to organic solvents and 40 not exposed. All those exposed presented at least 5 years of exposure to solvents. Hepatitis B and C, known hepatic disease, comorbidities, use of alcohol, illicit drugs or hepatotoxic medications, smoking, body mass index >30, female sex and age (<18 or >65) were excluded from the sample. Results indicated that elevated ALT was more frequent in the exposed group compared to controls: 33% vs. 10.5%, with a statistical significance (p < 0.05). Thiobarbituric acid reactive substances were significantly elevated (p < 0.01) in the exposed group in comparison to controls. Antioxidant enzymes were more elevated in the exposed group compared to controls: SOD 7.29 (4.30-8.91) USOD/mg of protein vs. 3.48 (2.98-5.28) USOD/mg of protein and GST 2.57 µmol/min/mg of protein (1.80-4.78) vs. 1.81 µmol/min/mg of protein (1.45- 2.30) µM/min/mg of protein. The results suggest an association between exposure to organic solvents and hepatotoxicity.

The prevalence of gastrointestinal disorders, such as constipation, has been increasing. Genetic factors and lifestyle are some of the etiologies of this issue, affecting the health of the population. Natural products have properties that contribute to health maintenance and health promotion, including reduction of the inflammatory process. Hancornia speciosa , popularly known as mangaba, is an abundant and native fruit in the Brazilian Cerrado, commercialized for culinary purposes and used because of its pharmacological properties. The objective of this study was to evaluate if the supplementation of different concentrations of mangaba pulp can improve intestinal motility and bowel health in Wistar rats. Forty male rats were divided into five groups. The experiment lasted 14 days and the groups were tested with water, industrialized laxative jelly made from tamarind as medication, or mangaba at 5, 10, and 15 mL/kg of body weight. Food intake, weight gain, ion balance, intestinal motility, and histopathological analysis of the small intestine, large intestine, and liver were evaluated. Supplementation of mangaba pulp at its highest concentration (15 mL/kg body weight) caused a 15% increase in the distance traveled by the charcoal meal, and a decrease in serum magnesium levels and white cells in both the small and large intestines. The results suggest that mangaba pulp presents laxative, anti-inflammatory properties and that its consumption is beneficial and should be encouraged.

Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug that is safe at therapeutic doses. However, acetaminophen overdose can be fatal. Currently, the only treatment available is the N-acetyl cysteine. The diterpene kaurenoic acid (ent-kaur-16-en-19-oic acid, KA) is the major constituent of Sphagneticola trilobata (L.) Pruski. KA presents anti-inflammatory, anti-nociceptive and antioxidant properties. In this study, we evaluated the efficacy of KA in a model of acetaminophen-induced hepatotoxicity. KA increased, in a dose-dependent manner, the survival rate after acetaminophen overdose. KA reduced acetaminophen-induced hepatic necrosis and ALT and AST levels. KA decreased acetaminophen-induced neutrophil and macrophage recruitment, oxidative stress and the production of IL-33, TNF-α and IL-1β, alongside with normalisation of IL-10 levels in the liver. Therefore, KA showed preclinical efficacy in acetaminophen-induced hepatotoxicity and lethality.

Microcystin's (MCs) are toxins produced by several groups of cyanobacteria, in water bodies throughout the world, in a process which is being intensified by human action. Among the variants of MCs, MC-LR stands out for its distribution and toxicity. MCs are potent inhibitors of protein phosphatases 1 and 2 A, which causes disruption of the cytoskeleton and consequent cell death. They can also alter the antioxidant system and induce oxidative stress in various organs of many species. There is, however, a lack of information about the effects of MCs on the antioxidant system and oxidative damage in Brazilian fishes. This study evaluated the effect of microcystin-LR on the antioxidant system in liver and gills of the Brazilian fish Brycon amazonicus, after 48 h of i.p injection of 100 μg MC-LR.kg -1 body mass. The liver exhibited increases in the activity of GST (74%) and GPx (217%), and a 47% decrease in SOD activity, with no changes in CAT values. In the gills of fish exposed to MC-LR, CAT and GPx activities did not show significant changes, while SOD and GST activity decreased by 66% and 37%, respectively. The GSH content did not change significantly in the liver, however, a decrease of 43% was observed in the gills. Oxidative damage measured by protein oxidation (PC) and lipoperoxidation (LPO) showed significant effects in both tissues. In hepatic tissue, there was no change in PC levels but LPO increased by 116%. Conversely, in the gills LPO levels did not change but PC increased by 317%. In conclusion, these data show that MC-LR induces oxidative damage in both tissues but in different ways, with being liver most sensitive to LPO and gills to PC. This also suggests that the gills are most sensitive to oxidative stress than liver, due to the inhibition of its antioxidant responses following MC-LR exposure., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Three species of freshwater Brazilian fishes (pacu, Piaractus mesopotamicus; piavussu, Leporinus macrocephalus, and curimbatá, Prochilodus lineatus) were exposed to an acute dose of 5 ppm methyl parathion organophosphate pesticide. Three to five individuals per species were exposed, one at a time, to 40 liters tap water spiked with Folidol 600. Pesticide concentrations and cholinesterase (ChE) activities were evaluated in serum, liver, brain, heart, and muscle. The bioconcentration of methyl parathion was similar for all studied fishes. Brain tissue showed the highest pesticide concentration, reaching 80 ppm after exposure for 30 min to methyl parathion. Three to 5 hours of 5 ppm methyl parathion exposure provoked the death of all P. lineatus at 92% brain AChE inhibition, whereas fish from the other two species survived for up to 78 hours with less than 80% brain AChE inhibition. Our results indicate that acute toxic effects of methyl parathion to fish are correlated with brain AChE sensitivity to methyl paraoxon.

The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is used in the traditional medicine systems for treating bacterial, fungal, parasitic and inflammatory conditions. The aim of this study was to evaluate the antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia) in multiple rodent organs subjected to intoxication with cadmium chloride. A total of 40 Wistar rats (8 weeks old, 250 g) were distributed into eight groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium exposed group (Cd); cadmium exposure and treated with extract at 62.5 mg/kg/day; cadmium exposure and treated with extract at 125 mg/kg/day; cadmium exposure and treated with extract at 250 mg/kg/day; cadmium exposure and treated with ethyl acetate fraction at 62.5 mg/kg/day. For evaluating the toxicogenetic potential of mimosa, two groups were included in the study being treated with extract at 250 mg/kg/day and acetate fraction of mimosa at 62 mg/kg/day, only. Extract of mimosa at concentrations of 62.5 and 125 mg decreased DNA damage in animals intoxicated with cadmium when compared to cadmium group. In a similar manner, treatment with ethyl acetate fraction of mimosa at 62.5 mg concentration in animals previously exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar manner, the treatment with ethyl acetate fraction reduced DNA damage in liver cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated with 125 mg of extract as well as those intoxicated to cadmium and treated with 62.5 of acetate fraction of mimosa. Taken together, our results indicate that mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral blood cells of rats as a result of antioxidant activity.

This study evaluated the toxicity of hexavalent and trivalent compounds of chromium to the pacu, Piaractus mesopotamicus, in acute exposures of 96 h through mortality and histopathological responses. Hexavalent potassium dichromate was more toxic than trivalent compounds of chromium chloride, chromium oxide and chromium carbochelate. Sufficient mortalities occurred only with potassium dichromate to yield an LC50 value at 124.2 mg L(-1). Hexavalent chromium caused reversible and irreversible lesions, which may affect organ functionality. Histopathological evaluation showed that trivalent chromium caused lesions of lower severity. Pacu subjected to different concentrations of chromium carbochelate showed no histopathological changes in the kidneys, liver, skin and gills, being similar to those of the control fish. Among the three sources of Cr(3+), only chromium chloride at 200 mg L(-1) resulted in mortality, which reached 100 % within the first 18 h. These findings confirm that trivalent chromium, when administered within recommended levels, may be used safely in aquaculture.

The aim of this study was to evaluate the effect of yacon (Smallanthus sonchifolius) (Poepp.& Endl.) on clinical parameters under diabetic conditions. The aqueous extract of yacon tuberous roots (YRAE; 0.76 g fructan kg⁻¹ body weight) was prepared at the moment of each administration. Thirty-two male rats were divided into four groups (n=8): control group (C); group that received YRAE (Y); untreated diabetic group (DM1); and diabetic group treated with YRAE (Y-DM1). The diabetes mellitus was induced by streptozotocin (60 mg kg⁻¹ body weight). The animals from Y2 and Y-DM1 received YRAE by gavage, at 7-day intervals, for 30 days. The aqueous extract of yacon roots decreased (p<0.05) the water and food intake in diabetic rats (Y-DM1). YRAE treatment reduced (p<0.05) glycaemia, total cholesterol, VLDL-c, LDL-c and triacylglycerol levels in diabetic rats (YRAE). HDL, urea and creatinine levels did not differ (p>0.05) between the Y and Y-DM1 groups. YRAE normalised alanine aminotransferase (ALT) activity, when comparing DM1 and Y-DM1 rats, but had no effect on lactate dehydrogenase activity (LDH). In conclusion, YRAE was sufficient for controlling water and food consumption, hyperglycaemia and dyslipidaemia, and promote the reduction of the ALT, suggesting a hepatoprotective effect in rats with STZ-induced DM1., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This study investigated the relationship between contaminant body burden and the oxidative stress status of the gills and livers of two wild fish species in the Furnas Hydroelectric Power Station (HPS) reservoir (Minas Gerais, Brazil). Gills and livers presented similar pathways of metals and organochlorine bioaccumulation. During June, organochlorines were associated with lipid peroxidation (LPO), indicating oxidative stress due to the inhibition of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. In the most polluted areas, metal concentrations in the liver were associated with metallothionein. During December, contaminants in the gills and liver were associated with catalase activity and LPO. Aldrin/dieldrin was the contaminant most associated with oxidative damage in the livers of both species. This integrated approach shed light on the relationship between adverse biological effects and bioaccumulation of contaminants inputted by intensive agricultural practices and proved to be a suitable tool for assessing the environmental quality of man-made reservoirs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The relationship of NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms with mild elevation of liver biomarkers was investigated in individuals under anti-tuberculosis drug therapy. Tuberculosis outpatients (18-70 y) with (n=59) and without (n=40) mild increase of liver enzymes (MILE) at two-month treatment were selected. Blood samples were obtained for DNA extraction and evaluation of serum markers of liver function. NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms were detected by DNA sequencing, PCR-RFLP, and PCR multiplex. Frequency of NAT2*5/*5 genotype was higher in MILE than in non-MILE group (p=0.04). Patients carrying NAT2*5/*5 genotype had increased susceptibility to MILE (OR: 9.00, 95CI: 1.46-55.48, p=0.018). CYP2E1*5B allele (*1A/*5B plus *5B/*5B genotypes) carriers had a trend for reduced risk for MILE (OR: 0.34, 95CI: 0.11-1.03, p=0.056) that was confirmed by lower levels of liver markers than CYP2E1*1A/*1A carriers after treatment (p<0.05). Moreover, increased post-treatment ALT, AST and total bilirubin were associated with GSTM1*1/GSTT1*1 genotypes (p<0.05). Patients taking CYP2E1 inhibitors had increased susceptibility to MILE (OR: 7.39, 95CI: 1.93-28.29, p=0.003), which was independent of the studied polymorphisms. These results are suggestive that NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms and concomitant use of CYP2E1 inhibitors contribute to the susceptibility to mild alterations in liver enzymes in patients under anti-tuberculosis drug therapy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Glutathione S-transferase (GST) assays in non-mammalian organisms are usually conducted inappropriately, since no previous standardization of the optimal concentrations of proteins and substrates and adequate pH is conducted. Standardization is a key task to adjust enzyme assays at their kinetically correct maximal initial velocities, if one wants these velocities to indicate the amount of enzyme in a sample. In this paper GST assays were standardized in liver cytosol to compare seasonal GST levels in liver of mullet from two contaminated lagoons in the Rio de Janeiro to those from a reference bay. GST potential as a biomarker of sublethal intoxication in this species was also evaluated. Mullet liver GST levels assayed with substrates that corresponded to three different GST isoenzymes varied throughout the year. The differences indicated that mullets are suffering from sublethal intoxication from contaminants in these lagoons. Seasonal variations of activity were relevant, since these could indicate differences in xenobiotic input into the areas. An analysis of overall mullet health condition using a morphological index (the Fulton Condition Factor) and macroscopic abnormalities corroborated the differences in GST levels, with fish from one of the sites in worse overall health condition showing lower and significantly different FCF when compared to the reference site. Therefore, GST standardized activity levels are useful biomarkers of environmental contamination for mullet., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Few studies have investigated the bioaccumulation of persistent organic pollutants (POPs) in Brazilian native freshwater fish. In order to evaluate the bioavailability, potential risk to human exposure and the effects of POPs in the fish Hypostomus commersoni, muscle and liver samples of thirteen specimens were collected in a lake located in the city of Ponta Grossa (Parana State, Southern Brazil). Also, the liver and gills were considered for histopathological studies, and oxidative stress was investigated in the liver. Expressive concentrations of POPs were observed in the liver and muscle, with a total of 427 ± 78.7 and 69.2 ± 18.1 ng g(-1) dry weights of polychlorinated biphenyls (PCBs), respectively. Negative correlations between the concentration of several POPs and glutathione S-transferase and glucose-6-phosphate dehydrogenase were found. Otherwise, the cholinesterase activity in the muscle and brain presented positive correlations with the concentration of POPs. The hepatic bioaccumulation of some banned pesticides like aldrin, dieldrin and DDT was associated with various histopathological findings in the liver and gills. Necrotic areas, fibrosis, leukocyte infiltration, and the absence of macrophage centers were observed in the liver, indicating both chronic exposure and immunological suppression. Neoplasic changes were observed in the gills, confirming the carcinogenic potential reported for some of the investigated pollutants. The current work was the first to study the bioaccumulation of POPs in H. commersoni, an important species in ecological aspects and as a vehicle to human exposure to PCBs and organochlorine pesticides (OCPs).

Biological monitoring through animals exposed to pollutants using biomarkers provides a promising tool for the identification of pollutants that may cause damage to human health and/or to sustainability of ecosystems. The effects of pollutants in fish tissues are important tools to understand the impact of human activities in natural ecosystems. The aim of this work was to study the water quality of two estuarine lakes in Santa Catarina, Brazil (Camacho Lake and Santa Marta Lake). Geophagus brasiliensis is a species widely distributed in Brazil and was used in this work. Comet assays in peripheral red blood and kidney cells, micronucleus tests in peripheral red blood cells, measurements of acetylcholinesterase activity in axial muscle and histopathological analysis of liver were used as biomarkers. Three sampling campaigns were undertaken in November 2004, June 2005 and November 2005. Thirty adult animals were sampled from each of three different sites (P1--Santa Marta Lake, P2 and P3--Camacho Lake). A negative control was sampled in a non-polluted site at Costa Ecological Park, Paraná. The positive control for genotoxicity was obtained by treating animals with copper sulphate. The results showed that both studied lakes are impacted by potential genotoxic substances. Severe lesions in liver of G. brasiliensis were also observed. The inhibition of acetylcholinesterase activity suggests the presence of pesticides or metals in the studied sites. This work shows that the water quality of Santa Marta and Camacho Lakes have been compromised and further control source of pollutants into these ecosystems is required.

Histopathological alterations in liver have been widely used as a tool in studies for monitoring environmental quality. To evaluate the environmental quality in the Cachoeira river, five spots were monitored between the municipal districts of Itapé and Ilhéus, using liver histological analysis. The species chosen for analysis was Poecilia vivipara due to the fact that it is one of the most abundant in the sampling. The routine technique of inclusion and impregnation in paraffin was used, and the cuts were stained with Hematoxylin and Eosin (H & E). Histopathological alterations in the liver were evaluated semi-quantitatively and based on the severity of the lesions. The results of the histopathological alteration frequency together with the average taken from the Histopathological Alteration Index from points 1 (Vila de Itapé) and 2 (Fazenda Santa Amélia) showed that in this area the environment is more threatened because of some stressor agent, possibly contaminants that seem to be acting in the environment and endangering the health of fish. The statistic results demonstrated that there were no significant differences among points 1, 2 and 4, which means they are very similar to one another, and are ecologically endangered.

Diabetes mellitus promoted an overproduction of free radicals and an increased incidence of both diabetic nephropathy and liver disease. In this report, we evaluated the effects of Chinese and Brazilian propolis on streptozotocin-induced hepatorenal injury in rats. The results demonstrated that Chinese propolis-treated rats had a 7.4% reduction in the glycated hemoglobin (HbAlc) level compared with untreated diabetic rats. Additionally, Chinese propolis induced an increase in the serum superoxide dismutase (SOD) level significantly while Brazilian propolis raised serum SOD and reduced level of malonaldehyde (MDA) and nitric synthetase (NOS). Of the measurable decrease in serum alanine transaminase (ALT), aspartate transaminase (AST) and microalbuminuria demonstrated the propolis-mediated improvement of hepatorenal function, which was further confirmed by histological examination. We also observed that Chinese and Brazilian propolis increased hepatorenal glutathione peroxidase (GSH-px) level and inhibited MDA production significantly. These results suggested that propolis may prevent hepatorenal injury by inhibiting lipid peroxidation and enhancing the activities of antioxidant enzymes.

In order to investigate the potential risk of mercury and DDTs exposure to fish-eating human populations in Samuel Reservoir, not affected directly by gold-mining activities, the axial muscle of Cichla monoculus was analyzed. Twenty-nine and thirty adults individuals were collected respectively on February (rainy season) and August (dry season) 2007. The specimens were sacrificed by spinal section before sex identification, body weight and total length determination. For total mercury, DDT and DDE quantifications and cholinesterase activity samples of the axial muscle were frozen at -20°C, and for histopathological studies gill and liver were fixed in ALFAC solution for 16 h. A value of 48.2% and 33% of the individuals, respectively from rainy and dry seasons, presented mercury concentrations higher than the maximum established for safe human consumption (0.5 μg g⁻¹) by World Health Organization. A positive correlation between body weight and Hg concentration was observed only in individuals from the rainy season, but no correlation was observed to DDT and DDE from both seasons. Differently from that observed to mercury, DDT levels presented a significant difference between both studied seasons, but no correlation was observed for both mercury and DDTs and sex. The levels of DDTs in muscle of C. monoculus are under the maximum established by FAO-Alimentarius CODEX and Swedish Food Regulation for human consumption. The histopathological and neurotoxic findings showed that the wild population of fish is affected by chronic exposure to mercury, meaning risk also to fish-eating populations. Finally, the results showed that C. monoculus is an important vehicle for human exposure to mercury and DDTs in Samuel Reservoir and that it is necessary a continuous biomonitoring of the levels of both pollutants in order to manage the risk of exposure to human populations., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The aim of this study was to determine the feasibility of combining water quality analysis with different biomarkers to characterise the relationship between anthropogenic contamination and biotic response in the Sinos River, southern Brazil. Wistar rats were studied using three biomarkers combined with physical, chemical and microbiological analysis to assess the effects of pollution at four sampling sites. The induction of oxidative stress was quantified by MDA levels in peripheral blood, lymphocyte DNA damage was determined using the comet assay, and histopathological changes were analysed in the liver. After sampling, animals were allowed to drink the river water during a 48 hours period. No increase in oxidative stress and DNA damage was observed. However, liver damage was observed in the animals exposed to water samples, indicating that the Sinos River is contaminated with hepatotoxic substances. Water analyses confirmed that water quality decreased downriver.

Plants have contributed over the years to the discovery of various pharmacological products. Amongst the enormous diversity of herbs with remarkable medicinal use and further pharmacological potential, here in this report we evaluated pulp extracts from Eugenia dysenterica fruits and further identified the active principle involved in such laxative activity in rats. For protein isolation, fruits were macerated with an extraction solution following precipitation with (NH(4))(2)SO(4) (100%). After dialysis, the peptide was applied onto a reversed-phase semi-preparative HPLC column, and the major fraction was eluted with 26% and 66% acetonitrile. The evaluation of molecular masses by MALDI-TOF and Tris/Tricine SDS-PAGE of HPLC fractions showed the presence of a major peptide with approximately 7 kDa. The N-terminal amino acid peptide sequence was determined and showed no similarity to other proteins deposited in the Data Bank. Peptide from E. dysenterica was able to enhance rats' intestinal motility by approximately 20.8%, probably being responsible for laxative activity. Moreover, these proteins were non-toxic to mammals, as observed in histopathology and hemolytic analyses. In conclusion, results here reported indicate that, in the near future, proteins synthesized by E. dysenterica fruits could be utilized in the development of novel biotechnological pharmaceutics with laxative properties for use in chronic constipation and irritable bowel syndrome treatment., (Copyright 2010 Elsevier Inc. All rights reserved.)

After ingesting green leaves of T. micrantha, 2 horses showed apathy, locomotor deficit, blindness, recumbency, paddling, coma and death. The main gross findings were scattered haemorrhages, enhanced lobular pattern of the liver, and cerebral oedema. Histological changes included disseminated haemorrhages, massive hepatocellular necrosis, neuronal degeneration, Alzheimer type II astrocytes and cerebral perivascular oedema. Clinicopathological findings which were comparable with those observed in Trema micrantha poisoned ruminants, associated with epidemiological evidence suggested the diagnosis.Trema micrantha poisoning should be evaluated as a possible cause in the diagnosis of equine hepatopathy and occasional secondary encephalopathy.

Propolis (bee glue) is a complex mixture of natural substances that exhibits a broad spectrum of biological activities. As the possibility exists that it may exert a chemopreventive role against cancer development, the present study aimed to evaluate the chemopreventive influence of a Brazilian aqueous propolis extract (APE) in a rat two-stage (initiation-promotion) medium-term bioassay for chemical liver carcinogenesis. Male Wistar rats were sequentially initiated with diethylnitrosamine (DEN, 200mg/kgb.w.) and, 2 weeks later, exposed to a diet containing hexachlorobenzene (HCB, 100ppm) and to APE 0.1% through drinking water for 6 weeks. Appropriate control groups were also established. The animals were sacrificed at the weeks 8th and 30th when liver samples were processed to evaluate the development of altered hepatocyte foci (AHF) identified under hematoxylin and eosin (H&E) staining and by the immunohistochemical expression of the enzyme glutathione S-transferase placental form (GST-P). The results indicate that APE 0.1% did not protect against the development of any of the differentially identified putative preneoplastic foci in DEN-initiated animals, exposed or not to the promoting agent HCB. Also, APE 0.1% by itself did not significantly induce any AHF, what is in line with its already known absence of genotoxic potential. Our results indicate that an aqueous extract of Brazilian propolis did not exert chemoprevention on the hepatocarcinogenesis process chemically induced in the rat.

Objective: To evaluate liver function and hemostatic parameters in postmenopausal women who have chronic infection with the hepatitis C virus and climacteric symptoms and are undergoing hormone therapy (HT) (standard dose of transdermal continuous combined hormone therapy)., Design: Fifty out of 336 postmenopausal patients with chronic infection with the hepatitis C virus were selected. The non-inclusion criteria were other chronic or systemic liver diseases, severe vascular diseases, autoimmune diseases or malignant tumors. The patients were randomized into two groups: the HT group with 25 patients to be given transdermal hormone therapy (50 microg estradiol plus 170 microg norethisterone/day) and the control group with the other 25 patients (no medication). Hepatic tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total alkaline phosphatase, albumin, serum bilirubin) and hemostatic parameters (prothrombin time, factor V, fibrinogen) were evaluated at baseline and at 1, 4, 7 and 9 months of treatment., Results: No significant changes in parameters were found in the comparison between the treated group and the controls, except for a decrease in total alkaline phosphatase (p = 0.002), presumably due to changes in bone remodelling., Conclusions: There were no changes in liver function after a 9-month treatment with transdermal estradiol plus norethisterone in symptomatic postmenopausal patients with hepatitis C.

This study analyzed biochemical biomarkers of freshwater and estuarine fish species from Southern Brazil. It analyzed three organs (muscle, liver and gills), in four fish species (Micropogonias furnieri, Pimelodus pintado, Loricariichthys anus and Parapimelodus nigribarbis) in order to perform an environmental diagnosis. Obtained results showed that liver of L. anus and gills of M. furnieri presented higher total antioxidant capacity against peroxyl radicals during fall, whereas a clear seasonality was found for gill reduced glutathione (GSH) levels of all studied species, with higher concentration during spring. In terms of oxidative damage (TBARS), liver of M. furnieri and gills of P. nigribarbis showed higher TBARS levels during fall, whereas P. pintado showed the lowest TBARS value. Finally, a conspicuous seasonal effect was observed for purified and non-purified glutathione-S-transferase (GST), where minimum values were registered during fall, pointing to this season as one where fish species are less competent to perform detoxifying reactions.

The Vicuña oil tanker exploded in Paranaguá Bay (South of Brazil), during methanol unloading operations in front of Paranaguá Harbour, on November 15th, 2004, releasing a large amount of bunker oil and methanol. Two weeks after the accident, the acute effects of the Vicuña Oil Spill (VOS) were evaluated in the demersal catfish Cathorops spixii, comparing a contaminated (at the spill site) and a reference site inside the Bay. Data were compared to previous measurements, taken before the accident, in the same species, from the same sites. The physiological biomarkers were the ones that best reflected acute effects of the spill: plasma osmolality, chloride, calcium, magnesium, and potassium. Morphological (liver and gill histopathology) and genetic (piscine micronucleus and DNA strand breaks) biomarkers revealed that damage was already present in fishes from both reference and contaminated sites inside the Bay. Thus, the reference site is not devoid of contamination, as water circulation tends to spread the contaminants released into other areas of the Bay. Acute field surveys of oil spill effects in harbour areas with a long history of contamination should thus be viewed with caution, and whenever possible previous evaluations should be considered for proper appraisal of biomarker sensitivity, especially in mobile bioindicators such as fish.

Purpose: To determine the frequency of N-acetyltransferase 2 (NAT2) polymorphisms, the NAT2 acetylation profile and its relation to the incidence of gastrointestinal adverse drug reactions (ADRs), anti-tuberculosis (TB) drug-induced hepatotoxicity, and the clinical risk factors for hepatotoxicity in a population from Brazil., Methods: Two hundred and fifty-four Brazilian TB patients using isoniazid (INH), rifampicin (RMP), and pirazinamide (PZA) were tested in a prospective cohort study. NAT2 genotyping was performed by direct PCR sequencing. The association between gastrointestinal ADRs/hepatotoxicity and the NAT2 profile genotype was evaluated by univariate analysis and multiple logistic regression., Results: Of the 254 patients analyzed, 69 (27.2%) were slow acetylators and 185 (72.8%) were fast acetylators. Sixty-five (25.6%) patients were human immunodeficiency virus (HIV)-positive. Thirty-three (13%) and 14 (5.5%) patients developed gastrointestinal ADR and hepatotoxicity, respectively. Of the 14 hepatotoxicity patients, nine (64.3%) were slow acetylators and five (35.7%) were fast acetylators. Sex, age, presence of hepatitis C virus, alcohol abuse, and baseline aminotransferases were not found to be risk factors for hepatotoxicity. However, logistic regression analysis revealed that slow acetylator status and the presence of HIV (p < 0.05) were independent risk factors for hepatotoxicity., Conclusions: Our findings show that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-TB drugs.

Methylmercury is a potent toxic present in Amazonian fish species due to gold mining activities. In the present work, we investigated the morphological effects of methylmercury in liver and kidney of Hoplias malabaricus feeding contaminated prey fish over 70 days. Two groups of nine mature fish (tested and control) were acclimatized for four weeks to laboratory conditions and then the tested group fed prey fish previously contaminated at an additional level of 0.075 microg MeHg g(-1) at 5-day intervals and over 14 successive intervals whereas control group fed uncontaminated fish. H. malabaricus specimens were then dissected for chemical and morphological analyses. The low and realistic level of MeHg in the prey fish induced a low increase of total mercury in liver (1.8-fold) and muscle (2.2-fold). The biomagnification factor (Hg in predator/Hg in prey) reached 142 in liver and 21 in muscle and was indicative of a relatively fast contamination of internal organs by dietary exposure. The liver of exposed individuals presented leukocyte infiltration, increased number of melano-macrophage centers, necrotic areas and lesions in Disse's space. Evident disorder and chaos in cytoskeleton organization suggest a strong toxic effect in hepatocytes, such as organelles positioning and movement, vesicles traffic and secretion. Head kidney showed large necrosis areas, increased number of melano-macrophages centers, phagocytic areas, intercellular space among parenquimal cells and atypical cells. Injuries and damages to tissues suggest too slow defense mechanisms to immobilize or eliminate ingested methylmercury, demonstrating that the sensitivity of fish cells to methylmercury exposure is higher than it has been previously described in the literature.

Neotropical fish traíra (Hoplias malabaricus) were used to investigate the effects of dietary doses of metals through individual exposures to either inorganic lead(II) or methylmercury, respectively, 21 microg Pb2+g(-1) w.w. and 75 ng H(3)C-Hg+g(-1) w.w., every 5 days, for 70 days (14 doses). The erythrocyte delta-aminolevulinic acid dehydratase (ALAd) activity was inhibited after 14 doses of Pb2+ and H(3)C-Hg+. The muscle cholinesterase (ChE) activity was inhibited after 14 doses of H(3)C-Hg+. Damage in cytoskeleton and nuclei were observed after exposure to inorganic lead. Individuals exposed to H(3)C-Hg+ showed the presence of atypical granules and vesicles, cytoplasm disorganization, and mitochondria damages in hepatocytes also after 14 doses. The present results demonstrate that erythrocyte ALAd and muscle ChE activities can be used as long-term biomarkers of sublethal, subchronic, and trophic exposures to Pb2+, and H(3)C-Hg+ in fish. Also the morphological aspects described in the present work confirm the toxicity of both studied metals.

Methyl parathion (MP) is an organophosphorus insecticide used worldwide in agriculture and aquaculture due to its high activity against a broad spectrum of insect pests. The effect of a single exposure to 2 mg L(- 1) of a commercial formulation of MP (MPc: Folisuper 600(R), MP 600 g L(- 1)) on catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (LPO) of the liver, white muscle and gills of Brycon cephalus was evaluated after 96 h of treatment. MPc exposure resulted in a significant induction of SOD, CAT and GST activity in all tissues. However, the GPx activity decreased significantly in white muscle and gills, whereas no alterations were observed in hepatic GPx activity. MPc also induced a significant increase in LPO values in the white muscle and gills, while hepatic LPO levels did not show any significant alteration. The current data suggest that MPc has oxidative-stress-inducing potential in fish, and that gills and white muscle are the most sensitive organs of B. cephalus, with poor antioxidant potentials. The various parameters studied in this investigation can also be used as biomarkers of exposure to MPc.

Acute intoxication by seeding Crotalaria retusa occurred during the dry season, in a flock of 80 sheep, in the semi-arid region of the state of Paraiba, northeastern Brazil. Anorexia, severe depression, mild jaundice, incoordination and recumbence were observed in 16 sheep that died within 12 h. At necropsy the liver had a nutmeg appearance. Seeds of C. retusa were found in large amounts in the rumen of the dead animals. Histologic lesions of the liver were characterized by centrilobular necrosis. Seeds of C. retusa were given to six sheep at doses of 2.5 (two sheep), 5, 10, 20 and 40 g/kg bw (one sheep for each dose). Sheep ingesting 5-40 g/kg bw were killed when moribund, 38-120 h after the start of the administration. Clinical signs and gross and histologic lesions were similar to those observed in field outbreak. The seeds used in the experiment contained 1.4% of monocrotaline. It is concluded that hungry sheep can be affected spontaneously by acute monocrotaline intoxication when they ingest large amounts of C. retusa seeds in a short period of time.

The neotropical freshwater fish matrinxã, Brycon cephalus (Günther, 1869), was exposed to 1/3 of 96 h-LC50 of Folidol 600 (methyl parathion) for 96 h and allowed to recover for 24, 48, 96, and 192 h. Acetylcholinesterase (AChE), alanine aminotransferase (ALAT), aspartate aminotransferase (AAT), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), and glutamate dehydrogenase (GDH) were assayed in brain, liver, muscle, and plasma. Plasma and brain AChE activities were strongly inhibited (64% and 87%, respectively), remaining low in the brain during recovery. Liver ALAT decreased 59.4% and plasma ALAT increased 94.2%. This response, associated with GDH reduction during the recovery period, was attributed to impairment of amino acid metabolism and to liver damage. The increase of heart and plasma AAT suggested tissue injury. Liver and plasma LDH and MDH did not change during the exposure to Folidol, but liver MDH decreased 34% during recovery, indicating a failure of oxidative metabolism in such tissue. Hepatic glycogen and glucose levels decreased 80.4 and 55%, respectively, followed by glucose mobilization to the plasma. The hepatic and muscular profile of lactate after recovery suggested gluconeogenesis without tissue hypoxia. These results revealed that methyl parathion affects the intermediary metabolism of matrinxã and that the assayed enzymes can work as good biomarkers of organophosphorus pesticide contamination.

The effects of functional cytoglucopenia provoked by 2-deoxy-D-glucose (2-DG) were studied in adult Brycon cephalus, an omnivorous fish from the Amazon Basin in Brazil. Glycogen content in liver and muscle as well as plasmatic glucose, free fatty acids (FFA), insulin, and glucagon were measured. After 48 h fasting, an intraperitoneal saline injection (NaCl 0.6 g/100 ml) was administered to control fish, whereas the experimental group received 2-DG, dissolved in saline, in the dosage of 80 mg/kg (0.487 mmol/kg) or 150 mg/kg (0.914 mmol/kg) body weight; injection volume was 5 ml in all treatments. Blood and tissue samples were taken immediately before, and 2, 8, 10, and 24 h after administration of the drug or saline. Fish injected with both doses of 2-DG showed a marked increase in glycemia levels. Liver and muscle glycogen decreased after 2-DG administration and reached their lowest values 10-24 h after injection, while in control animals no significant changes were observed. Elevation in plasma glucagon was observed only in response to the maximum dosage of 2-DG administered, especially 10 h and 24 h post-injection. Plasma insulin levels were lower in animals treated with the glucose analogue but only statistically significant 24 h after drug administration. In conclusion, the administration of the non-metabolizable glucose analogue 2-DG in B. cephalus is a stimulus to generate responses towards an increase in the glucose available to tissues, which is a characteristic of a fasting situation. All the above data support the interest of 2-DG administration as a model to study carbohydrate metabolism adjustment mechanisms in fish.

The action of a barbatimão extract on hepatic energy metabolism was investigated using isolated mitochondria and the perfused rat liver. In mitochondria the barbatimão extract inhibited respiration in the presence of ADP and succinate. Stimulation occurred, however, after ADP phosphorylation (state IV respiration). The ADP/O and respiratory control ratios were reduced. The activities of succinate-oxidase, NADH-oxidase and the oxidation of ascorbate were inhibited. The ATPase of intact mitochondria was stimulated, but the ATPases of uncoupled and disrupted mitochondria were inhibited. In perfused livers the extract caused stimulation of oxygen consumption, inhibition of gluconeogenesis and stimulation of glycolysis. Glucose release due to glycogenolysis was stimulated shortly after the introduction of the extract, but inhibition gradually developed as the infusion was continued. Apparently the barbatimão extract impairs the hepatic energy metabolism by three mechanisms: (1) uncoupling of oxidative phosphorylation, (2) inhibition of mitochondrial electron transport, and (3) inhibition of ATP-synthase.

The in vivo protective effects of methanol extracts of eight South American medicinal plants traditionally used as antiinflammatory were determined by means of spontaneous lipid peroxidation of liver tissue in rats. The production of TBARS was reduced in a dose dependent manner for A. macrocarpa (IC50 = 132 mg/kg), A. urundeuva (IC50 = 176 mg/kg), C. reticulata (IC50 = 561mg/kg) and S. obtusifolium (IC50 = 918 mg/kg). The extracts of P. peltata and U. tomentosa were only effective at a high concentration (300 mg/kg), although these values were not significant. The lyophilized latex of C. lechleri decreased the production of TBARS at a 200 mg/kg dose, although pro-oxidant effects were observed at lower doses (50 mg/kg). The extract of H. pallida was pro-oxidant at lower concentrations (50 mg/kg)., (Copyright 2003 John Wiley & Sons, Ltd.)

The in vitro antioxidant and free radical scavenging properties in bark extracts of South American tree Copaifera reticulata Ducke. (Caesalpinaceae) were studied using different bioassays. Lipid peroxidation was assessed by means of the production of thiobarbituric acid reactive substances (TBARS) in rat liver homogenate. All the extracts tested were effective in this method. The highest activity was observed in the aqueous extract, showing an IC50 of 30 micrograms/ml. DNA sugar damage induced by Fe (II) salts was also used to determine the capacity of the samples to suppress hydroxyl radical-mediated degradation of DNA. Although all the extracts tested were effective in reducing oxidation of DNA, the highest activity was observed in the methanol extract, showing an IC50 of 2 micrograms/ml. Bioassay-guided fractionation of a total methanol extract monitored by luminol-enhanced chemiluminescence, together with structural elucidation using 13C NMR and FABMS, led to the identification of profisetinidin type tannins in a semi-pure fraction. The fraction containing the active compounds also reduced the production of TBARS in rat liver homogenates (IC50 = 530 micrograms/ml) and DNA damage (IC50 = 1 microgram/ml), suggesting that profisetinidins could be responsible for the free radical scavenging and antioxidant activities observed in the extracts.

In a feedlot of about 1,000 head of cattle, 146 animals died within a period of a few months affected by a disease characterized by anorexia, icterus, hemoglobinuria, constipation, or diarrhea. The clinical course of the disease lasted a few days. Postmortem findings were generalized icterus and a yellow discolored liver. The kidneys were dark brown, and the urinary bladder was filled with urine of the same dark-brown color. The main histopathological findings were centrolobular coagulative necrosis, apoptosis, bilestasis, and proliferation of bile ducts in the portal space. Changes in the kidneys included nephrosis and the presence of bile and precipitates, and cylinders of albumin and of hemoglobin in the uriniferous tubules. Liver samples, collected from 3 animals on which postmortem examinations were performed, had 2,008, 2,783 and 4,906 ppm copper in their dry matter. Two samples of poultry litter fed to the cattle contained 362 and 323 ppm copper. The green forage that formed the rest of their feed only had 4.7 ppm copper. Copper poisoning was diagnosed, most probably caused by feeding litter from poultry that had been fed a ration treated with copper sulfate to avoid aspergillosis.

The cytotoxicity of trans-dehydrocrotonin (DHC), an antiulcerogenic diterpene from Croton cajucara (Euphorbiaceae), was assessed on a V79 fibroblast cell line and on rat hepatocytes. Three independent endpoints for cytotoxicity were evaluated: DNA content, MTT reduction and neutral red uptake (NRU). For the V79 cells IC50 values of 253 and 360 microM were obtained for the NRU and MTT tests. The cytotoxic effect of DHC was time exposure dependent and no ability to recover after treatment was observed. For the rat hepatocytes IC50 values of 8, 300 and 400 microM for the MTT, DNA and NRU assays were obtained. The greater toxicity observed for the MTT test was inhibited when the experiment was performed using non-fresh hepatocytes in an age-dependent fashion. The treatment of V79 cells with the conditioned medium resulting after hepatocyte incubation with DHC showed an enhancement of MTT reduction without any evident toxic effects on fibroblasts. These results suggest that DHC has basal cytotoxic effects as observed on V79 fibroblasts and expresses a selective cytotoxicity after its metabolization by the hepatocytes. The bioactivation of DHC is mediated by cytochrome P450 and could generate metabolites that have no toxicity for V79 fibroblasts.

Myoporum laetum was collected in the municipalities of Rio Grande and Capao do Leao in winter and in Santa Vitoria in summer, autumn, winter and spring, in the state of Rio Grande do Sul, Brazil, and in the Department of Rocha, Uruguay, in winter and spring. The fresh green plant was fed to 17 sheep. All sheep developed clinical signs, except 1 that consumed only 4 g/kg bw daily during 10 d. Five of the 9 sheep dosed with 40 g/kg died. Four sheep dosed with plants from Uruguay at 40 g/kg, 6 sheep dosed with 20 g/kg, and 1 sheep dosed with 2 daily doses of 8 g/kg survived. Clinical signs were anorexia, restlessness, ruminal stasis, jaundice and dry feces with mucus or blood. All surviving sheep had photodermatitis in the face, ears, eyes and lips. Histologic lesions were characterized by periportal liver necrosis. Serum levels of AST, GGT and bilirubin were increased. M laetum from Uruguay was less toxic, suggesting a variation in toxicity among plants from different regions.

Riedeliella graciflora is a plant mainly found in southeast South America and related to bovine mortality in Sao Paulo State, Brazil. Our laboratory showed that cattle intoxicated with 10 g R graciflora leaves/kg had organ congestion, edema and hemorrhage. The aim of this study was to determine which laboratory animal species would present the same lesions found in cattle. We also studied the effects of administering parts of the fruits or leaves po, sc, ip or im. All the laboratory species developed organ congestion, edema and hemorrhage and severe nephrosis regardless which plant part was given or the route of administration used. The effects were more intense in animals dosed with R graciflora fruits ip.