The mechanism of patulin's cytotoxicity and the antioxidant activity of indole tetramic acids

Riley, R T; Showker, J L

doi:10.1016/0041-008X(91)90195-K

Title: The mechanism of patulin's cytotoxicity and the antioxidant activity of indole tetramic acids

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Abstract

In LLC-PK1 cells exposed to patulin (50 microM), lipid peroxidation, abrupt calcium influx, extensive blebbing, and total LDH release appeared to be serially connected events with each representing a step in the loss of structural integrity of the plasma membrane. The aforementioned patulin-induced events were prevented by concurrent incubation with butylated hydroxytoluene, deferoxamine, and cyclopiazonic acid, a fungal metabolite. Patulin also caused depletion of nonprotein sulfhydryls, increased 86Rb+ efflux, dome collapse, and eventually the loss of cell viability. These events were not prevented by antioxidants, results consistent with the hypothesis that they were also serially connected but occurring parallel to those previously mentioned. The earliest events observed in patulin-treated cells were the decrease in nonprotein sulfhydryls and increase in 86Rb+ efflux (5 min) which occurred before statistically significant alterations in protein-bound sulfhydryls. The increased potassium efflux (86Rb+ efflux) occurred via a pathway distinct from BaCl2, quinine, or tetraethylammonium sensitive potassium channels. This is the first published report of the antioxidant activity of indole tetramic acids (cyclopiazonic acid and cyclopiazonic acid imine). The protective effect of tetramic acids in LLC-PK1 cells was restricted to indole tetramic acids, and their prevention of lipid peroxidation did not involve iron chelation. The results ofmore »« less

Authors:

Riley, R T; Showker, J L ^[1]

Toxicology and Mycotoxins Research Unit, U.S. Department of Agriculture/Agricultural Research Service, Athens, GA (USA)

Publication Date:: Sat Jun 01 00:00:00 EDT 1991

OSTI Identifier:: 5596020

Resource Type:: Journal Article

Journal Name:: Toxicology and Applied Pharmacology; (United States)

Additional Journal Information:: Journal Volume: 109:1; Journal ID: ISSN 0041-008X

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; ANTIBIOTICS; BIOLOGICAL EFFECTS; ANTIOXIDANTS; CALCIUM COMPOUNDS; MEMBRANE TRANSPORT; ANIMAL CELLS; ATP; BIOLOGICAL PATHWAYS; DEFEROXAMINE; KIDNEYS; LACTATE DEHYDROGENASE; LIPIDS; METABOLISM; METABOLITES; MUSCLES; PHARMACOLOGY; POTASSIUM; RATS; RUBIDIUM 86; TRACER TECHNIQUES; ALKALI METALS; ALKALINE EARTH METAL COMPOUNDS; AMINES; ANIMALS; ANTI-INFECTIVE AGENTS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BODY; CHELATING AGENTS; DAYS LIVING RADIOISOTOPES; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; ELEMENTS; ENZYMES; HEMIACETAL DEHYDROGENASES; INTERMEDIATE MASS NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; MAMMALS; METALS; MINUTES LIVING RADIOISOTOPES; NUCLEI; NUCLEOTIDES; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; ORGANS; OXIDOREDUCTASES; RADIOISOTOPES; RODENTS; RUBIDIUM ISOTOP; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats


                    Riley, R T, and Showker, J L. The mechanism of patulin's cytotoxicity and the antioxidant activity of indole tetramic acids.  United States: N. p., 1991. 
        Web.  doi:10.1016/0041-008X(91)90195-K.

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                    Riley, R T, & Showker, J L. The mechanism of patulin's cytotoxicity and the antioxidant activity of indole tetramic acids.  United States.  https://doi.org/10.1016/0041-008X(91)90195-K

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                    Riley, R T, and Showker, J L. 1991.  
        "The mechanism of patulin's cytotoxicity and the antioxidant activity of indole tetramic acids".  United States.  https://doi.org/10.1016/0041-008X(91)90195-K.

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@article{osti_5596020,

  title        = {The mechanism of patulin's cytotoxicity and the antioxidant activity of indole tetramic acids},

  author       = {Riley, R T and Showker, J L},

  abstractNote = {In LLC-PK1 cells exposed to patulin (50 microM), lipid peroxidation, abrupt calcium influx, extensive blebbing, and total LDH release appeared to be serially connected events with each representing a step in the loss of structural integrity of the plasma membrane. The aforementioned patulin-induced events were prevented by concurrent incubation with butylated hydroxytoluene, deferoxamine, and cyclopiazonic acid, a fungal metabolite. Patulin also caused depletion of nonprotein sulfhydryls, increased 86Rb+ efflux, dome collapse, and eventually the loss of cell viability. These events were not prevented by antioxidants, results consistent with the hypothesis that they were also serially connected but occurring parallel to those previously mentioned. The earliest events observed in patulin-treated cells were the decrease in nonprotein sulfhydryls and increase in 86Rb+ efflux (5 min) which occurred before statistically significant alterations in protein-bound sulfhydryls. The increased potassium efflux (86Rb+ efflux) occurred via a pathway distinct from BaCl2, quinine, or tetraethylammonium sensitive potassium channels. This is the first published report of the antioxidant activity of indole tetramic acids (cyclopiazonic acid and cyclopiazonic acid imine). The protective effect of tetramic acids in LLC-PK1 cells was restricted to indole tetramic acids, and their prevention of lipid peroxidation did not involve iron chelation. The results of this study demonstrate that cyclopiazonic acid is a potent inhibitor of azide-insensitive, ATP-dependent, a23187-sensitive calcium uptake by the lysate of LLC-PK1 cells. This result is consistent with the hypothesis that the endoplasmic reticulum calcium transport ATPase is a sensitive target for cyclopiazonic acid in LLC-PK1 cells.},

  doi          = {10.1016/0041-008X(91)90195-K},

  url          = {https://www.osti.gov/biblio/5596020},
  journal      = {Toxicology and Applied Pharmacology; (United States)},

  issn         = {0041-008X},

  number       = ,

  volume       = 109:1,

  place        = {United States},

  year         = {Sat Jun 01 00:00:00 EDT 1991},

  month        = {Sat Jun 01 00:00:00 EDT 1991}

}

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