Stereocontrolled Elaboration of Natural (−)-Polycavernoside A, a Powerfully Toxic Metabolite of the Red AlgaPolycavernosatsudai

2000 ◽  
Vol 122 (4) ◽  
pp. 619-631 ◽  
Author(s):  
Leo A. Paquette ◽  
Louis Barriault ◽  
Dmitri Pissarnitski ◽  
Jeffrey N. Johnston
Keyword(s):  
Toxic Metabolite ◽  
Polycavernoside A

ChemInform Abstract: Stereocontrolled Elaboration of Natural (-)-Polycavernoside A, a Powerfully Toxic Metabolite of the Red Alga Polycavernosa tsudai.

ChemInform ◽  
2010 ◽  
Vol 31 (19) ◽  
pp. no-no
Author(s):  
Leo A. Paquette ◽  
Louis Barriault ◽  
Dmitri Pissarnitski ◽  
Jeffrey N. Johnston
Keyword(s):  
Red Alga ◽  
Toxic Metabolite ◽  
Polycavernoside A

scholarly journals Peroxisome Senescence in Human Fibroblasts

2002 ◽  
Vol 13 (12) ◽  
pp. 4243-4255 ◽  
Author(s):  
Julie E. Legakis ◽  
Jay I. Koepke ◽  
Chris Jedeszko ◽  
Ferdous Barlaskar ◽  
Laura J. Terlecky ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Protein Import ◽  
Human Fibroblasts ◽  
Toxic Metabolite ◽  
Age Related ◽  
Peroxisomal Targeting ◽  
Targeting Signal ◽  
Effects Of Aging ◽  
Antioxidant Enzyme Catalase ◽  
Import Receptor

The molecular mechanisms of peroxisome biogenesis have begun to emerge; in contrast, relatively little is known about how the organelle functions as cells age. In this report, we characterize age-related changes in peroxisomes of human cells. We show that aging compromises peroxisomal targeting signal 1 (PTS1) protein import, affecting in particular the critical antioxidant enzyme catalase. The number and appearance of peroxisomes are altered in these cells, and the organelles accumulate the PTS1-import receptor, Pex5p, on their membranes. Concomitantly, cells produce increasing amounts of the toxic metabolite hydrogen peroxide, and we present evidence that this increased load of reactive oxygen species may further reduce peroxisomal protein import and exacerbate the effects of aging.

ChemInform Abstract: Total Synthesis of the Marine Toxin Polycavernoside A (I) via Selective Macrolactonization of a Trihydroxy Carboxylic Acid.

ChemInform ◽  
2010 ◽  
Vol 32 (52) ◽  
pp. no-no
Author(s):  
James D. White ◽  
Paul R. Blakemore ◽  
Cindy C. Browder ◽  
Jian Hong ◽  
Christopher M. Lincoln ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Total Synthesis ◽  
Marine Toxin ◽  
Polycavernoside A

Total Synthesis of (−)-Polycavernoside A: Suzuki–Miyaura Coupling Approach

2012 ◽  
Vol 14 (12) ◽  
pp. 3186-3189 ◽  
Author(s):  
Yusuke Kasai ◽  
Takanori Ito ◽  
Makoto Sasaki
Keyword(s):  
Total Synthesis ◽  
Polycavernoside A ◽  
Coupling Approach

Intranasal Toxicity of BMS-181885, A Novel 5-HT1 Agonist

1999 ◽  
Vol 18 (5) ◽  
pp. 285-296
Author(s):  
Gene E. Schulze ◽  
Jim E. Proctor ◽  
Mark A. Dominick ◽  
Amy E. Weiss ◽  
Oliver P. Flint ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nasal Mucosa ◽  
Olfactory Epithelium ◽  
Mucosal Injury ◽  
Separate Experiment ◽  
Toxic Metabolite ◽  
Respiratory Epithelial Cells ◽  
Nasal Injury ◽  
Respiratory Epithelial ◽  
Dose Dependent

One-month intranasal toxicity studies were conducted with BMS-181885 at doses of 1.5, 9, or 15 mg/animal/day in rats and 4, 24, or 40 mg/animal/day in monkeys. A 1-month intermittent intranasal toxicity study was also conducted in monkeys at doses of 3, 6, and 12 mg/animal 3 days per week. BMS-181885 was generally well tolerated in rats but resulted in dose-dependent nasal mucosal injury, primarily characterized by subacute inflammation of the nasal mucosa, and degeneration, single-cell necrosis, and/or erosion of the olfactory epithelium and, to a lesser extent, the respiratory epithelium. In monkeys, daily BMS-181885 administration was well tolerated and produced similar dose-dependent nasal injury primarily characterized by subacute inflammation of the nasal mucosa with degeneration and erosion of the olfactory epithelium. In a separate experiment, intermittent administration also resulted in dose-dependent nasal injury. In cultured rat nasal mucosal cells, BMS-181885 was toxic to olfactory epithelial cells with a range of mean IC50s between 44 and 291 μM. In contrast, BMS-181885 had no effect on respiratory epithelial cells up to its maximum solubility. Cytochrome P450 inhibition had no effect on the toxicity of BMS-181885 in olfactory epithelial cells but produced dose-dependent toxicity in respiratory epithelial cells, which was not present previously. The in vitro data suggest that parent drug, rather than a toxic metabolite, caused the drug-associated nasal mucosal injury.

Molecular cytotoxic mechanisms of chlorpromazine in isolated rat hepatocytes

2013 ◽  
Vol 91 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Stephanie L. MacAllister ◽  
Cheryl Young ◽  
Anna Guzdek ◽  
Nickholas Zhidkov ◽  
Peter J. O'Brien
Keyword(s):  
First Generation ◽  
Rat Hepatocytes ◽  
Antipsychotic Agents ◽  
Toxic Metabolite ◽  
Quinone Oxidoreductase ◽  
Metabolite Formation ◽  
Isolated Rat Hepatocytes ◽  
Electron Reduction ◽  
Catalyzed Oxidation ◽  
Isolated Rat

Chlorpromazine (CPZ), a member of the largest class of first-generation antipsychotic agents, is known to cause hepatotoxicity in the form of cholestasis and hepatocellular necrosis in some patients. The mechanism of CPZ hepatotoxicity is unclear, but is thought to result from reactive metabolite formation. The goal of this research was to assess potential cytotoxic mechanisms of CPZ using the accelerated cytotoxicity mechanism screening (ACMS) technique with freshly isolated rat hepatocytes. This study identified CPZ cytotoxicity and inhibition of mitochondrial membrane potential (MMP) to be concentration-dependent. Furthermore, inhibition of cytochrome P450s (CYPs), including CYP2D1 and 1A2, delayed CPZ cytotoxicity, suggesting a role for CYP activation of CPZ to a toxic metabolite(s) in this model. Metabolism studies also demonstrated glucuronide and glutathione (GSH) requirement for CPZ detoxification in hepatocytes. Inactivating the 2-electron reduction pathway, NAD(P)H quinone oxidoreductase (NQO1), caused a significant increase in hepatocyte susceptibility to CPZ, indicating quinoneimine contribution to CPZ cytotoxicity. Nontoxic concentrations of peroxidase/H2O2 (inflammatory model) increased cytotoxicity in CPZ-treated hepatocytes and caused additional mitochondrial toxicity. Inflammation further depleted GSH and increased oxidized glutathione (GSSG) levels. Results suggest activation of CPZ to reactive metabolites by 2 pathways in hepatocytes: (i) a CYP-catalyzed quinoneimine pathway, and (ii) a peroxidase-catalyzed oxidation of CPZ to CPZ radicals.

New LC method using radioactivity detection for analysis of toxic metabolite of acetaminophen (Paracetamol)

2002 ◽  
Vol 56 (1) ◽  
pp. S75-S78
Author(s):  
E. Hazai ◽  
E. Simon-Trompler ◽  
G. Czira ◽  
L. Vereczkey ◽  
K. Monostory
Keyword(s):  
Toxic Metabolite

scholarly journals Cross-Feeding of a Toxic Metabolite in a Synthetic Lignocellulose-Degrading Microbial Community

2021 ◽  
Vol 9 (2) ◽  
pp. 321
Author(s):  
Jessica A. Lee ◽  
Alyssa C. Baugh ◽  
Nicholas J. Shevalier ◽  
Brandi Strand ◽  
Sergey Stolyar ◽  
...  
Keyword(s):  
Resource Competition ◽  
Plant Biomass ◽  
Lignocellulose Degradation ◽  
Toxic Metabolite ◽  
Growth Requirements ◽  
Mutualistic Interaction ◽  
Metabolite Exchange ◽  
Future Work ◽  
Biomass Transformation ◽  
Complex Organic

The recalcitrance of complex organic polymers such as lignocellulose is one of the major obstacles to sustainable energy production from plant biomass, and the generation of toxic intermediates can negatively impact the efficiency of microbial lignocellulose degradation. Here, we describe the development of a model microbial consortium for studying lignocellulose degradation, with the specific goal of mitigating the production of the toxin formaldehyde during the breakdown of methoxylated aromatic compounds. Included are Pseudomonas putida, a lignin degrader; Cellulomonas fimi, a cellulose degrader; and sometimes Yarrowia lipolytica, an oleaginous yeast. Unique to our system is the inclusion of Methylorubrum extorquens, a methylotroph capable of using formaldehyde for growth. We developed a defined minimal “Model Lignocellulose” growth medium for reproducible coculture experiments. We demonstrated that the formaldehyde produced by P. putida growing on vanillic acid can exceed the minimum inhibitory concentration for C. fimi, and, furthermore, that the presence of M. extorquens lowers those concentrations. We also uncovered unexpected ecological dynamics, including resource competition, and interspecies differences in growth requirements and toxin sensitivities. Finally, we introduced the possibility for a mutualistic interaction between C. fimi and M. extorquens through metabolite exchange. This study lays the foundation to enable future work incorporating metabolomic analysis and modeling, genetic engineering, and laboratory evolution, on a model system that is appropriate both for fundamental eco-evolutionary studies and for the optimization of efficiency and yield in microbially-mediated biomass transformation.

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