DNA damage in organs of mice treated acutely with patulin, a known mycotoxin.
Patulin, a known mycotoxin, is considered a significant contaminant in apples, apple-derived products and feeds. This study investigated the genotoxic effects of patulin in multiple organs (brain, kidney, liver and urinary bladder) of mice using an in vivo comet assay. We assessed the mechanism underlying this genotoxicity by measuring the GSH content and the thiobarbituric acid-reactive species (TBARS) level. Male CF-1 mice were given 1.0-3.75 mg/kg patulin intraperitoneally. The effect of patulin was dose-dependent and the highest patulin dose induced DNA strand breaks in the brain (damage index, DI, in hippocampus increased from 36.2 in control animals to 127.5), liver (44.3-138.4) and kidneys (31.5-99); decreased levels of GSH (hippocampus--from 46.9 to 18.4 nmol/mg protein); and an increase in lipid peroxidation (hippocampus--from 5.8 to 20.3 MDA equivalents/mg protein). This finding establishes an interrelationship between the pro-oxidant and genotoxic effects of patulin. Pre-treatment administration of N-acetyl-cysteine reduced patulin-induced DNA damage (hippocampus--DI from 127.5 to 39.8) and lipid peroxidation (hippocampus--20.3 to 12.8 MDA equivalents/mg protein) by restoring cellular GSH levels, reinforcing the positive relationship between patulin-induced GSH depletion and DNA damage caused by systemic administration of this mycotoxin.
Programa de Pós-Graduação em Toxicologia Aplicada, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil.
Flávia Terezinha
FT
de Melo
Iuri Marques
IM
de Oliveira
Samuel
S
Greggio
Jaderson Costa
JC
Dacosta
Temenouga Nikolova
TN
Guecheva
Jenifer
J
Saffi
João Antonio Pêgas
JA
Henriques
Renato Moreira
RM
Rosa
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018384:Oxidative Stress; D010365:Patulin / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
D010365:Patulin; D005978:Glutathione; D000111:Acetylcysteine