Early toxic effects of fumonisin B1 in rat liver.
Mycotoxin fumonisin B(1) (FB(1)) is hepatotoxic and carcinogenic in experimental animals. It is known that long-term exposure of experimental animals to FB(1) causes apoptosis and lipid peroxidation. In this study, male adult Wistar rats were treated with single FB(1) doses (5, 50, and 500 microg/kg b.w.) and sacrificed 4, 24, and 48 hours after treatment. Parameters of oxidative stress, histopathological changes, and DNA damage were monitored in the liver of treated and control animals. Parameters of oxidative stress were not affected by such treatment. A significant increase in apoptotic cells appeared in animals when 5 microg/kg b.w. dose was given and sacrificed after 24 hours with further increase at higher doses. In contrast to the number of mitotic figures and karyomegaly seen mostly at lower FB(1) doses, necrosis was the prominent feature at higher doses. Significant increase in liver cells DNA mobility was observed 48 hours following treatment with 50 and 500 microg/kg b.w. as compared to control (tail length 15.2 +/- 0.3, 16.4 +/- 0.5, and 13.5 +/- 0.1 mum, respectively). Tail intensity appeared to be more sensitive parameter for detecting DNA damage even at 5 microg/kg b.w. after 48 hours (1.69 +/- 0.27% DNA; control 0.59 +/- 0.11% DNA). This study proved that FB(1)-induced DNA damage is time- and dose-dependent, and that it could be caused in Wistar rats by a single dose.
Domijan
Am
A
Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Zeljezic
D
D
Peraica
M
M
Kovacevic
G
G
Gregorovic
G
G
Krstanac
Z
Z
Horvatin
K
K
Kalafatic
M
M
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D037341:Fumonisins / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D008940:Mitotic Index; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D037341:Fumonisins; C056933:fumonisin B1