Search results for "Hepatotoxin"
showing 10 items of 10 documents
Bioaccumulation of hepatotoxins : A considerable risk in the Latvian environment
2014
Abstract The Gulf of Riga, river Daugava and several interconnected lakes around the City of Riga, Latvia, form a dynamic brackish-freshwater system favouring occurrence of toxic cyanobacteria. We examined bioaccumulation of microcystins and nodularin-R in aquatic organisms in Latvian lakes, the Gulf of Riga and west coast of open Baltic Sea in 2002–2007. The freshwater unionids accumulated toxins efficiently, followed by snails. In contrast, Dreissena polymorpha and most lake fishes (except roach) accumulated much less hepatotoxins. Significant nodularin-R concentrations were detected also in marine clams and flounders. No transfer of nodularin-R and microcystins between lake and brackish …
The Biosynthesis of Rare Homo-Amino Acid Containing Variants of Microcystin by a Benthic Cyanobacterium
2019
Microcystins are a family of chemically diverse hepatotoxins produced by distantly related cyanobacteria and are potent inhibitors of eukaryotic protein phosphatases 1 and 2A. Here we provide evidence for the biosynthesis of rare variants of microcystin that contain a selection of homo-amino acids by the benthic cyanobacterium Phormidium sp. LP904c. This strain produces at least 16 microcystin chemical variants many of which contain homophenylalanine or homotyrosine. We retrieved the complete 54.2 kb microcystin (mcy) gene cluster from a draft genome assembly. Analysis of the substrate specificity of McyB1 and McyC adenylation domain binding pockets revealed divergent substrate specificity …
Separation and Biochemical Characterization of Rat Liver Parenchymal Cell Subpopulations
1988
Parenchymal cells within the hepatic lobules of the rat are morphologically and biochemically heterogeneous (Shank et al., 1959; Novikoff, 1959; Loud, 1968; Jungermann and Katz, 1982). It has been previously shown that the concentration of cytochrome P-450 and the activities of most cytochrome P-450-dependent monooxygenases are relatively higher in the centrilobular regions than in the periportal regions of the rat liver (Baron et al., 1978; Gooding et al., 1978; Baron and Kawabata, 1983); further, these studies revealed that pretreatment of the animals with phenobarbital intensified this gradation across the liver lobule, whereas after administration of 3-methylcholanthrene the concentrati…
Effect of ivermectin on the liver of gilthead sea bream Sparus aurata: a proteomic approach.
2010
23 p., 2 tablas, 4 figuras y bibliografía
Hepatoprotective Effect of Steroidal Glycosides From Dioscorea villosa on Hydrogen Peroxide-Induced Hepatotoxicity in HepG2 Cells
2018
Dioscorea villosa, commonly known as “Wild Yam” and native to North America, is well documented for its pharmacological properties due to the presence of steroidal glycosides. However, the hepatoprotective potential of these compounds has not been studied so far. The present investigation was aimed to study the hepatoprotective effect of the steroidal glycosides from D. villosa against H2O2, a known hepatotoxin, in human liver cell line (HepG2). Cytotoxicity assessment was carried out in cells exposed to various concentrations (10–50 μM) of compounds for 24 h using MTT assay and morphological changes. All tested compounds were known and among them, spirostans (zingiberensis saponin I, diosc…
Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent.
2018
Abstract Cholestasis represents a major subtype of drug-induced liver injury and novel preclinical models for its prediction are needed. Here we used primary human hepatocytes (PHH) from different donors in 2D-sandwich (2D-sw) and/or 3D-spheroid cultures to study inter-individual differences in the response towards cholestatic hepatotoxins after short-term (48–72 hours) and long-term repeated exposures (14 days). The cholestatic liabilities of drugs were determined by comparing cell viability upon exposure to the highest non-cytotoxic drug concentration in the presence and absence of a non-cytotoxic concentrated bile acid mixture. In 2D-sw culture, cyclosporine A and amiodarone presented cl…
LC-MS untargeted metabolomic analysis of drug-induced hepatotoxicity in HepG2 cells
2015
Hepatotoxicity is the number one cause for agencies not approving and withdrawing drugs for the market. Drug-induced human hepatotoxicity frequently goes undetected in preclinical safety evaluations using animal models. Human-derived in vitro models represent a common alternative to in vivo tests to detect toxic effects during preclinical testing. Most current in vitro toxicity assays rely on the measurement of nonspecific or low sensitive endpoints, which result in poor concordance with human liver toxicity. Therefore, making more accurate predictions of the potential hepatotoxicity of new drugs remains a challenge. Metabolomics, whose aim is to globally assess all the metabolites present …
Production of High Amounts of Hepatotoxin Nodularin and New Protease Inhibitors Pseudospumigins by the Brazilian Benthic Nostoc sp. CENA543
2017
Nostoc is a cyanobacterial genus, common in soils and a prolific producer of natural products. This research project aimed to explore and characterize Brazilian cyanobacteria for new bioactive compounds. Here we report the production of hepatotoxins and new protease inhibitors from benthic Nostoc sp. CENA543 isolated from a small, shallow, saline-alkaline lake in the Nhecolandia, Pantanal wetland area in Brazil. Nostoc sp. CENA543 produces exceptionally high amounts of nodularin-R. This is the first free-living Nostoc that produces nodularin at comparable levels as the toxic, bloom-forming, Nodularia spumigena. We also characterized pseudospumigins A-F, which are a novel family of linear te…
Effect of polybrominated biphenyls on bromobenzene lethality in mice.
1977
Polybrominated biphenyls (PBBs) are inducers of hepatic microsomal cytochrome P450 and P1 450 in rats and mice. The purpose of this study was to determine, in mice, the effect of PBBs on the lethality of the hepatotoxin bromobenzene. Female NMRI mice were administered a single ip injection of 150 mg/kg PBBs and other mice received phenobarbital (PB), 100 mg/kg daily for 3 days, or 3‐methylcholanthrene (MC), 20 mg/kg daily for 3 days. At 24 hr after PB or MC and 24, 48, and 96 hr after PBBs animals received 3,150 mg/kg bromobenzene ip (LD85) and the time to death was recorded. Both PB and MC enhanced bromobenzene lethality and decreased the median time to death (LT50) from 23 hr in controls …
Effects of a preparation containing a standardized ginseng extract combined with trace elements and multivitamins against hepatotoxin-induced chronic…
1987
A preparation containing a standardized ginseng extract which has been shown to exert anti-hepatotoxic activity in vitro, combined with trace elements and multi-vitamins was compared to placebo in 24 elderly out-patients with toxin-induced (alcohol and drugs) chronic liver disease in order to evaluate its effect on liver function. Each patient was blindly treated either with the preparation containing ginseng extract or placebo for 12 weeks. The preparation containing ginseng extract significantly modified bromsulphthalein retention and blood zinc levels when compared to pre-treatment levels and to placebo. Serum bile acids, and γ-glutamyl transpeptidase before and after a fatty meal were …