In vitro evaluation of the chemoprotective action mechanisms of leontopodic acid against aflatoxin B1 and deoxynivalenol-induced cell damage.
Several in vitro studies showed that free radical scavengers possess chemopreventive properties against mycotoxin-induced cell damage which are at least partially associated with the induction of phase II detoxifying enzymes and antioxidant enzymes like glutathione S-transferase (GST) and glutathione peroxidase (GPx). The aim of this project was to study the chemopreventive effects of leontopodic acid (LA), a potent natural occurring free radical scavenger isolated from the aerial parts of Leontopodium alpinum. Different mycotoxins were evaluated in two different cell lines on the basis of their specific toxicity: aflatoxin B1 (AFB1) on HepG2 cells and deoxynivalenol (DON) on U937 cells. Cell viability and reactive oxygen species concentration were determined, and the effects of pre-treatment with LA on these parameters were investigated together with the GST and GPx activity as well as the concentration of reduced glutathione. The results show that LA protects U937 cells from DON-induced cell damage but not HepG2 cells from AFB1. Moreover LA is able to enhance GPx activity in U937, but not GST activity in HepG2. We hypothesize that the increase in detoxifying enzymes is probably the main mechanism of antioxidant mediated chemoprevention.
Costa
Stefano
S
Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126, Italy. stefano.costa6@unibo.it
Schwaiger
Stefan
S
Cervellati
Rinaldo
R
Stuppner
Hermann
H
Speroni
Ester
E
Guerra
Maria Clelia
MC
D016604:Aflatoxin B1 / Q000633:toxicity*; D019659:Asteraceae / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D018197:Hepatoblastoma; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D016166:Free Radical Scavengers; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014255:Trichothecenes; C539083:leontopodic acid; D016604:Aflatoxin B1; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione; C007262:deoxynivalenol; D005937:Glucaric Acid