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Journal Article 2012; 33(Suppl 3): 161-165 PubMed PMID: 23353861 Citation  Keywords:  Animals, Bacterial Toxins:toxicity, Biomass, Body Weight, Carcinogens:toxicity, Chemical and Drug Induced Liver Injury:epidemiology, Coturnix, Cyanobacteria:chemistry, Dose-Response Relationship, Drug, Hepatocytes:drug effects, Lethal Dose 50, Male, Marin.   

OBJECTIVES: Previous studies using oral administration of environmentally relevant doses of cyanobacterial biomass containing microcystins (MCs) induced only sub-lethal effects in experimental birds. Therefore, the objective of this study was to obtain data on avian high-dose toxicity of MCs and compute LD50, if possible, following the natural oral route of administration.

DESIGN: Responses of birds to single high-dose exposure to MCs were evaluated in fourteen-day old Japanese quail males (Coturnix coturnix japonica) with average body weight of 50 g which were randomly divided into five groups. Birds from four experimental groups were administered 7.5 ml of cyanobacterial biomass suspension containing increasing MCs quantities of 2500, 5000, 10000, and 20000 µg/kg using oral gavage. Controls received an equal dose of drinking water instead of the test substance. Birds were observed for clinical signs of acute toxicity. Survivors were killed on day 5 to obtain body and liver weights. A five-grade semi-quantitative system for histopathological liver damage scoring was used to compare cyanobacterial-biomass-exposed birds against controls.

RESULTS: No mortality occurred during the period of five days post exposure in both control and MCs-exposed groups and this high-dose experiment failed to provide data to compute the LD50. Nevertheless, marked sub-lethal effects were recognised in the damage of liver that included dose-dependent changes in the body/liver ratios and morphological changes ranging from mild vacuolar dystrophy to focal liver necroses in the highest exposure group. Hepatic lesions were mainly observed in the pericentral area of the liver.

CONCLUSIONS: Though maximum cyanobacterial biomass dose rates that could be administered to birds of the size were used in the present experiment and more pronounced hepatic lesions than after exposure to environmentally relevant doses were observed, birds would probably have survived unless killed for histopathology on day 5 of exposure. These results provide support to previously reported data on sub-lethal effects following exposure to cyanobacterial biomass containing MCs in birds and mortality occurring only in birds under combined action with other stressors....

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Journal Article 2012; 33(Suppl 3): 113-119 PubMed PMID: 23353853 Citation  Keywords:  Animals, Chemical and Drug Induced Liver Injury:metabolism, Dose-Response Relationship, Drug, Gills:drug effects, Hepatocytes:drug effects, Herbicides:pharmacokinetics, Kidney:drug effects, Models, Biological, Thiobarbituric Acid Reactive Substances:metab.   

OBJECTIVES: Terbuthylazine belongs to the group of symmetrical triazine herbicides used extensively in agriculture and non-agricultural sites, primarily to control broadleaf and some grassy weeds that have become ubiquitous contaminants of the environment. The aim of this study was to assess the impact of terbuthylazine in surface waters on fish under experimental conditions. The effects of subchronic exposure to terbuthylazine on fish growth and the development of histopathological changes in selected organs (gill, kidney, liver), and on the activity of some biochemical parameters - glutathione S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) and on the concentration of thiobarbituric acid reactive substances (TBARS) in Danio rerio were investigated during a 28 day toxicity test.

METHODS: Juvenile growth tests were performed on Danio rerio according to OECD guideline No. 215. Fish at the age of 30 days were exposed for 28 days to a range of sublethal concentrations of terbuthylazine (0.55 - environmental concentration, 150, 400, 700 and 1000 μg/L).

RESULTS: There were no significant differences (p<0.05) between the specific growth rates (r) of the test groups and control group. Histopathological examination revealed pathological changes only in the liver in fish exposed to terbuthylazine at concentrations of 700 and 1000 μg/L. Significant differences (p<0.05) in activities of biochemical markers were found in GST (400, 700 and 1000 μg/L), GR (700 and 1000 μg/L), significant differences (p<0.05) of TBARS concentration were found at 1000 μg/L.

CONCLUSIONS: Based on the results of growth rate, the histopathological examination of selected organs, and the results of biochemical parameters, it was found that the environmental concentration of terbuthylazine did not have any effects on juvenile D. rerio. The values of NOEC and LOEC for terbuthylazine for juvenile D. rerio were 150 μg/L and 400 μg/L....

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Evaluation Studies 2011; 32(Suppl 1): 89-94 PubMed PMID: 22167213 Citation  Keywords:  Animals, Behavior, Animal:drug effects, Dose-Response Relationship, Drug, Environmental Exposure, Hepatocytes:drug effects, Herbicides:pharmacology, Kidney:drug effects, Simazine:pharmacology, Survival Analysis, Toxicity Tests, Subchronic:statistics & num.   

OBJECTIVES: Simazine is a triazine herbicide which has been used for a long period in agriculture and in the aquatic environment for control of weeds and algae. The aim of this study was to investigate the effects of subchronic exposure to simazine on growth and the development of histopathological changes in selected organs (gills, kidney, liver) in Danio rerio.

METHODS: Juvenile growth tests were performed on D. rerio according to the OECD method No. 215. Fish at the age of 20 days were exposed to the environmental simazine concentration commonly detected in Czech rivers (0.06 μg.L-1) and a range of sublethal concentrations of simazine (0.6, 6.0 and 60.0 μg.L-1) for 28 days.

RESULTS: There were no significant differences (p<0.05) between the specific growth rates (r) of the test groups and those of both control groups. Histopathological examination revealed pathological changes in fish exposed to a simazine concentration of 60.0 μg.L-1. The values of NOEC and LOEC of simazine were 6.0 μg.L-1 and 60.0 μg.L-1.

CONCLUSIONS: The environmental concentration of simazine in Czech rivers did not have any effects on the growth and development of histopathological changes in D. rerio....

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Journal Article 2011; 32(Suppl 2): 41-50 PubMed PMID: 22101882 Citation  Keywords:  Animals, Cell Separation, Cell Survival:drug effects, Culture Media, DNA, Complementary:biosynthesis, Dioxoles:pharmacology, Fatty Acids:metabolism, Gene Expression:drug effects, Genistein:pharmacology, Hepatocytes:drug effects, In Vitro Techniques, Indic.   

OBJECTIVES: Effects of bioactive compounds on expression of genes involved in lipid metabolism and fatty acid composition were investigated in Atlantic salmon (Salmo salar L.) primary hepatocytes.

METHODS: Five treatments were investigated: I) genistein 0.005 mM, II) genistein 0.025 mM, III) lipoic acid 0.2 mM, IV) sesamin/episesamin 0.05 mM, V) sesamin 0.05 mM and compared to controls. The relative expression of genes involved in lipid homeostasis was analysed after 12h and 48h.

RESULTS: Incubation with lipoic acid, sesamin and episesamin/sesamin for 48h had significant effect on all analysed genes involved in lipid uptake, β-oxidation, elongation and desaturation, some effects were detected on the expression of peroxisome prolifertor-activated receptor (PPARs). Also effects on the fatty acid composition were found.

CONCLUSION: The strongest effect of bioactive copounds on hepatocyte gene expression was detected after 48 hours....

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Journal Article 2008; 29(5): 644-648 PubMed PMID: 18987600 Citation  Keywords:  Animals, Antioxidants, Apoptosis:drug effects, Cell Count, Cell Death, Cell Separation, Chitin:analogs & derivatives, Comet Assay, DNA:drug effects, DNA Damage:drug effects, Female, Glucans:pharmacology, Hepatocytes:drug effects, Hydrogen Peroxide:toxicit.   

OBJECTIVES: Utilizing primary rat hepatocytes we investigated the potential antimutagenic and anti-cytotoxic effects of carboxymethyl chitin-glucan (CM-CG) with respect to oxidative stress induced by the model free-radical-generating compounds hydrogen peroxide (H2O2) or 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). Different kinds of CM-CG action were studied by two different treatment protocols: a. pre-incubation of freshly isolated hepatocytes with the potential anti-mutagen followed by exposure to the oxidant or b. simultaneous treatment of hepatocytes with the potential anti-mutagen and the oxidant.

METHODS: As a measure of genotoxicity, the percentages of DNA in tails of comets by single cell gel electrophoresis were evaluated. The cytotoxicological endpoints analysed were the cell density (number of cells/cm2), and the percentages of apoptotic and necrotic cells.

RESULTS: H2O2 and DMNQ, causing DNA single-strand breaks via the formation of *OH radicals, have been demostrated to induce both genotoxic and cytotoxic effects in primary rat hepatocytes resulting in increased percentages of DNA in tails of comets, and increased frequencies of apoptotic and necrotic cells accompanied by a decreased cell density. Further investigations were therefore focussed on possible modifications of these parameters by CM-CG. The results obtained clearly demonstrate that CM-CG (applied before and during treatment) protects primary rat hepatocytes against the genotoxic and cytotoxic effects of oxidative stress (H2O2 or DMNQ), whereas CM-CG itself has no effect on the endpoints of genotoxicity and cytotoxicity studied.

CONCLUSION: Our results indicate that carboxymethyl chitin-glucan represents a natural fungal polysaccharide that can inhibit the genotoxicity and cytotoxicity of experimentally induced oxidative stress in primary rat hepatocytes....

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Journal Article 2002; 23(4): 335-340 PubMed PMID: 12195237 Citation  Keywords:  Animals, Anticonvulsants:pharmacology, Cell Division:drug effects, DNA:biosynthesis, Drug Interactions, Hepatocytes:drug effects, Male, Melatonin:pharmacology, Mutagens:pharmacology, Necrosis, Nitroparaffins:pharmacology, Propane:analogs & derivatives, Ra.   

OBJECTIVES: 2-Nitropropane (2-NP) is mutagenic in a number of short-term mutagenicity assays in vitro and in vivo, and is a potent hepatocarcinogen in rats. Many studies have determined that differences in the metabolism and disposition of the chemicals that produce mutagenicity were not responsible for their observed carcinogenic differences, but that carcinogenicity correlated with the ability of the respective isomer to induce cell proliferation in the target organ.

METHODS: Three groups of male rats (control, 2-NP-treated [4 mmol/kg] and 2-NP + melatonin [10 mg/kg]) were used in the current study. Cell proliferation was quantitated by incorporation of 3H-thymidine, detected by autoradiography, into newly synthesized DNA. Histopatholgical study was carried out to investigate the morphological changes.

RESULTS: Twenty four hours after 2-NP administration, there was an increase in the labelling index (LI) and grain count per labelled nucleus (GC/N) in the hepatocytes of 2-NP-injected rats versus those of control animals. The increase was 69.5% in LI and 29.4% in GC/N. Melatonin treatment, 30 minutes preceding 2-NP, reduced the increase in LI (44.4%) and GC/N (20.7%) when compared with 2-NP-treated rats. Histopathology revealed multiple focal areas of necrosis in the liver following 2-NP injection. In the lung, there was a mucinous degeneration of the bronchial epithelium. Melatonin treatment restored the histopathological changes in both the liver and lung and they are more or less normal.

CONCLUSION: Overall, these results seem to indicate that the stimulatory effect of 2-NP on the cellular proliferation and the rate of DNA synthesis in the liver may be one of mechanisms by which the carcinogen induces its carcinogenic action. Also, melatonin treatment strongly protects the studied organs against the toxic effect of 2-NP....

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