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

Journal Article · Sat Jun 01 00:00:00 EDT 1991 · Toxicology and Applied Pharmacology; (United States)

DOI:https://doi.org/10.1016/0041-008X(91)90195-K· OSTI ID:5596020

Riley, R T; Showker, J L ^[1]

---

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

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.

• OSTI ID: 5596020
• Journal Information: Toxicology and Applied Pharmacology; (United States), Vol. 109:1; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

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