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Sidney J Stohs - One of the best experts on this subject based on the ideXlab platform.

  • Potential Chemoprotectant Activity of Mechanism‐based Glycosidase Inhibitors against Ricin Toxicity in Chinese Hamster Ovary and Macrophage J774A.1 Cell Cultures
    Journal of Applied Toxicology, 1996
    Co-Authors: E A Hassoun, Debasis Bagchi, Victoria F Roche, Sidney J Stohs
    Abstract:

    The abilities of the triacetylated galacto- and gluco-derivatives of 2-deoxy-2-fluoro-D-pyranosyl fluoride as well as α- and β-N-bromoacetyl-D-galactopyranosylamine to inhibit the cytotoxicity of ricin in vitro in macrophage J774A.1 and Chinese hamster ovary (CHO) cell lines were determined. Leakage of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) from the cells into the culture media were used as indicators of ricin cytotoxicity. The potential Chemoprotectants were used in concentrations ranging from 10 -8 to 10 -4 g ml -1 . Of the four potential mechanism-based, site-specific glycosidase inhibitors that were tested, 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-β-D-glucopyranosyl fluoride exhibited the greatest Chemoprotectant activity. The ricin-induced LDH release was inhibited in a concentration-dependent manner by this compound, with the LDH leakage returning to control values in the presence of the highest concentration of this Chemoprotectant in both cell cultures when given 4 h prior to ricin. This compound exhibitied a small but significant inhibition of AST release from both cell cultures when given simultaneously with ricin. 3,4,6-Tri-O-acetyl-2-deoxy-2-fluoro-β-D-galactopyranosyl fluoride exhibited a small but significant chemoprotective effect only at the highest concentration in both cell cultures when given simultaneously with ricin. Both the α- and β-isomers of N-bromoacetyl-D-galactopyranosylamine exhibited activity against ricin toxicity in the CHO cell line, with the β-isomer exhibiting greatest activity. The β-isomer exhibited greater cytotoxicity in the absence of ricin, as demonstrated by the release of both enzymes from the cultured CHO cells. Further studies will be required to assess the utility of these compounds as Chemoprotectants against ricin toxicity in vivo.

  • potential Chemoprotectant activity of mechanism based glycosidase inhibitors against ricin toxicity in chinese hamster ovary and macrophage j774a 1 cell cultures
    Journal of Applied Toxicology, 1996
    Co-Authors: E A Hassoun, Debasis Bagchi, Victoria F Roche, Sidney J Stohs
    Abstract:

    The abilities of the triacetylated galacto- and gluco-derivatives of 2-deoxy-2-fluoro-D-pyranosyl fluoride as well as α- and β-N-bromoacetyl-D-galactopyranosylamine to inhibit the cytotoxicity of ricin in vitro in macrophage J774A.1 and Chinese hamster ovary (CHO) cell lines were determined. Leakage of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) from the cells into the culture media were used as indicators of ricin cytotoxicity. The potential Chemoprotectants were used in concentrations ranging from 10 -8 to 10 -4 g ml -1 . Of the four potential mechanism-based, site-specific glycosidase inhibitors that were tested, 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-β-D-glucopyranosyl fluoride exhibited the greatest Chemoprotectant activity. The ricin-induced LDH release was inhibited in a concentration-dependent manner by this compound, with the LDH leakage returning to control values in the presence of the highest concentration of this Chemoprotectant in both cell cultures when given 4 h prior to ricin. This compound exhibitied a small but significant inhibition of AST release from both cell cultures when given simultaneously with ricin. 3,4,6-Tri-O-acetyl-2-deoxy-2-fluoro-β-D-galactopyranosyl fluoride exhibited a small but significant chemoprotective effect only at the highest concentration in both cell cultures when given simultaneously with ricin. Both the α- and β-isomers of N-bromoacetyl-D-galactopyranosylamine exhibited activity against ricin toxicity in the CHO cell line, with the β-isomer exhibiting greatest activity. The β-isomer exhibited greater cytotoxicity in the absence of ricin, as demonstrated by the release of both enzymes from the cultured CHO cells. Further studies will be required to assess the utility of these compounds as Chemoprotectants against ricin toxicity in vivo.

  • Release of enzymes by ricin from macrophages and chinese hamster ovary cells in culture
    Toxicology Methods, 1993
    Co-Authors: E A Hassoun, Victoria F Roche, Sidney J Stohs
    Abstract:

    Ricin selectively depletes hepatic Kupffer's cells (macrophages) in mice, and is cytotoxic in vitro to Chinese hamster ovary (CHO) cells, the L 929 (mouse fibroblast) cell line, and rat bone marrow macrophages. Therefore, the toxicity of ricin to the macrophage J-744A. 1 and CHO cell lines was assessed by determining the release of lactate dehydrogenase (LDH), aspartate aminotransfer-ase (AST), and alanine aminotransferase (ALT). Both dose- and time-dependent increases in the release of LDH and AST were observed. In macrophages, concentrations > 10-9 g ricin/ml inhibited the release of ALT at 48- and 72-h incubation times, whereas ALT release from CHO cells was inhibited by all concentrations of ricin at 24 and 48 h. The results indicate that the release of LDH and AST from macrophage and CHO cell lines may be useful in studies involving the molecular mechanism of toxicity of ricin as well as in assessing the efficacy of potential Chemoprotectant agents against ricin.

  • an assessment of potential Chemoprotectant activity against ricin toxicity by mechanism based glycosidase inhibitors in macrophage j744a 1 cell cultures
    Toxicon, 1992
    Co-Authors: E A Hassoun, Debasis Bagchi, Victoria F Roche, Sidney J Stohs
    Abstract:

    The abilities of potential Chemoprotectants to inhibit cytotoxicity of ricin have been determined in vitro, using the macrophage cell line J744A.1. Six compounds were tested: α-and β-galactopyranosylamine; N-bromoacetyl-α-d-galactopyranosylamine; N-bromoacetyl-β-D-galactopyranosylamine; N-bromoacetylglucopyranosylamine; and N-bromoacetylmannopyranosylamine. Of the six compounds which were tested, only N-bromoacetyl-α-D-galactopyranosylamine and N-bromoacetyl-β-D-galactopyranosylamine exhibited significant activity against ricin toxicity, as indicated by the release of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST). The α-isomer provided greater protection against ricin toxicity and also exhibited less inherent cytotoxicity in the absence of ricin, as compared to the β-isomer. Neither the α-and β-galactopyranosylamines nor the glucose and mannose analogs were promising as potential Chemoprotectants.

  • Evaluation of potential Chemoprotectants against microcystin-LR hepatotoxicity in mice.
    Journal of Applied Toxicology, 1991
    Co-Authors: S J Hermansky, Victoria F Roche, Sidney J Stohs, Z. M. Eldeen, K. A. Mereish
    Abstract:

    Microcystin-LR (MCLR) is a potent cyclic heptapeptide hepatotoxin produced by the blue-green algae, Microcystis aeruginosa. Toxic blooms of this cyanobacteria have been reported throughout the temperate world. In spite of the potential economic loss and health hazard posed by this toxin, few studies on the development of an antidote have been conducted. Thus, a number of biologically active compounds were tested in mice for effectiveness in preventing the toxicity of a lethal dose of MCLR (100 micrograms kg-1). Efficacy was evaluated based upon the percentage of surviving mice, time to death and serum lactate dehydrogenase activity 45 min after treatment with the toxin. The biologically active compounds were separated into groups based upon proposed mechanisms of action. Enzyme induction by phenobarbital but not by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in partial protection against toxicity. Calcium channel blockers, free-radical scavengers and water-soluble antioxidants produced little protection against toxicity. The membrane-active antioxidants vitamin E and silymarin, as well as glutathione and the monoethyl ester of glutathione, produced significant protection from lethality. Rifampin and cyclosporin-A, both immunosuppressive and membrane-active agents, which also block the bile acid uptake system of hepatocytes, produced complete protection from the toxicity of MCLR. Thus, lipophilic antioxidants provide partial protection against MCLR toxicity while cyclosporin-A and rifampin are highly effective and potentially useful antidotes. The toxicity of MCLR may depend upon stimulation of the immune system and may be mediated by membrane alterations.

Voravit Ratanatharathorn - One of the best experts on this subject based on the ideXlab platform.

S Cronin - One of the best experts on this subject based on the ideXlab platform.

E A Hassoun - One of the best experts on this subject based on the ideXlab platform.

  • Potential Chemoprotectant Activity of Mechanism‐based Glycosidase Inhibitors against Ricin Toxicity in Chinese Hamster Ovary and Macrophage J774A.1 Cell Cultures
    Journal of Applied Toxicology, 1996
    Co-Authors: E A Hassoun, Debasis Bagchi, Victoria F Roche, Sidney J Stohs
    Abstract:

    The abilities of the triacetylated galacto- and gluco-derivatives of 2-deoxy-2-fluoro-D-pyranosyl fluoride as well as α- and β-N-bromoacetyl-D-galactopyranosylamine to inhibit the cytotoxicity of ricin in vitro in macrophage J774A.1 and Chinese hamster ovary (CHO) cell lines were determined. Leakage of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) from the cells into the culture media were used as indicators of ricin cytotoxicity. The potential Chemoprotectants were used in concentrations ranging from 10 -8 to 10 -4 g ml -1 . Of the four potential mechanism-based, site-specific glycosidase inhibitors that were tested, 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-β-D-glucopyranosyl fluoride exhibited the greatest Chemoprotectant activity. The ricin-induced LDH release was inhibited in a concentration-dependent manner by this compound, with the LDH leakage returning to control values in the presence of the highest concentration of this Chemoprotectant in both cell cultures when given 4 h prior to ricin. This compound exhibitied a small but significant inhibition of AST release from both cell cultures when given simultaneously with ricin. 3,4,6-Tri-O-acetyl-2-deoxy-2-fluoro-β-D-galactopyranosyl fluoride exhibited a small but significant chemoprotective effect only at the highest concentration in both cell cultures when given simultaneously with ricin. Both the α- and β-isomers of N-bromoacetyl-D-galactopyranosylamine exhibited activity against ricin toxicity in the CHO cell line, with the β-isomer exhibiting greatest activity. The β-isomer exhibited greater cytotoxicity in the absence of ricin, as demonstrated by the release of both enzymes from the cultured CHO cells. Further studies will be required to assess the utility of these compounds as Chemoprotectants against ricin toxicity in vivo.

  • potential Chemoprotectant activity of mechanism based glycosidase inhibitors against ricin toxicity in chinese hamster ovary and macrophage j774a 1 cell cultures
    Journal of Applied Toxicology, 1996
    Co-Authors: E A Hassoun, Debasis Bagchi, Victoria F Roche, Sidney J Stohs
    Abstract:

    The abilities of the triacetylated galacto- and gluco-derivatives of 2-deoxy-2-fluoro-D-pyranosyl fluoride as well as α- and β-N-bromoacetyl-D-galactopyranosylamine to inhibit the cytotoxicity of ricin in vitro in macrophage J774A.1 and Chinese hamster ovary (CHO) cell lines were determined. Leakage of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) from the cells into the culture media were used as indicators of ricin cytotoxicity. The potential Chemoprotectants were used in concentrations ranging from 10 -8 to 10 -4 g ml -1 . Of the four potential mechanism-based, site-specific glycosidase inhibitors that were tested, 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-β-D-glucopyranosyl fluoride exhibited the greatest Chemoprotectant activity. The ricin-induced LDH release was inhibited in a concentration-dependent manner by this compound, with the LDH leakage returning to control values in the presence of the highest concentration of this Chemoprotectant in both cell cultures when given 4 h prior to ricin. This compound exhibitied a small but significant inhibition of AST release from both cell cultures when given simultaneously with ricin. 3,4,6-Tri-O-acetyl-2-deoxy-2-fluoro-β-D-galactopyranosyl fluoride exhibited a small but significant chemoprotective effect only at the highest concentration in both cell cultures when given simultaneously with ricin. Both the α- and β-isomers of N-bromoacetyl-D-galactopyranosylamine exhibited activity against ricin toxicity in the CHO cell line, with the β-isomer exhibiting greatest activity. The β-isomer exhibited greater cytotoxicity in the absence of ricin, as demonstrated by the release of both enzymes from the cultured CHO cells. Further studies will be required to assess the utility of these compounds as Chemoprotectants against ricin toxicity in vivo.

  • Release of enzymes by ricin from macrophages and chinese hamster ovary cells in culture
    Toxicology Methods, 1993
    Co-Authors: E A Hassoun, Victoria F Roche, Sidney J Stohs
    Abstract:

    Ricin selectively depletes hepatic Kupffer's cells (macrophages) in mice, and is cytotoxic in vitro to Chinese hamster ovary (CHO) cells, the L 929 (mouse fibroblast) cell line, and rat bone marrow macrophages. Therefore, the toxicity of ricin to the macrophage J-744A. 1 and CHO cell lines was assessed by determining the release of lactate dehydrogenase (LDH), aspartate aminotransfer-ase (AST), and alanine aminotransferase (ALT). Both dose- and time-dependent increases in the release of LDH and AST were observed. In macrophages, concentrations > 10-9 g ricin/ml inhibited the release of ALT at 48- and 72-h incubation times, whereas ALT release from CHO cells was inhibited by all concentrations of ricin at 24 and 48 h. The results indicate that the release of LDH and AST from macrophage and CHO cell lines may be useful in studies involving the molecular mechanism of toxicity of ricin as well as in assessing the efficacy of potential Chemoprotectant agents against ricin.

  • an assessment of potential Chemoprotectant activity against ricin toxicity by mechanism based glycosidase inhibitors in macrophage j744a 1 cell cultures
    Toxicon, 1992
    Co-Authors: E A Hassoun, Debasis Bagchi, Victoria F Roche, Sidney J Stohs
    Abstract:

    The abilities of potential Chemoprotectants to inhibit cytotoxicity of ricin have been determined in vitro, using the macrophage cell line J744A.1. Six compounds were tested: α-and β-galactopyranosylamine; N-bromoacetyl-α-d-galactopyranosylamine; N-bromoacetyl-β-D-galactopyranosylamine; N-bromoacetylglucopyranosylamine; and N-bromoacetylmannopyranosylamine. Of the six compounds which were tested, only N-bromoacetyl-α-D-galactopyranosylamine and N-bromoacetyl-β-D-galactopyranosylamine exhibited significant activity against ricin toxicity, as indicated by the release of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST). The α-isomer provided greater protection against ricin toxicity and also exhibited less inherent cytotoxicity in the absence of ricin, as compared to the β-isomer. Neither the α-and β-galactopyranosylamines nor the glucose and mannose analogs were promising as potential Chemoprotectants.

C Raith - One of the best experts on this subject based on the ideXlab platform.