Immunotoxicity of nivalenol after subchronic dietary exposure to rats.
Immunobiological effects of nivalenol (NIV), a trichothecene mycotoxin produced by Fusarium nivale, were examined in male F344 rats after 90-day dietary exposure at doses of 0, 0.4, 1.5, and 6.9 mg/kg body weight/day (0, 6.25, 25 and 100 ppm, respectively) in a subchronic toxicity study. With regards to the serum immunoglobulin levels, a slight increase of IgM was observed only at 6.9 mg/kg (26% increase), while levels of IgG and IgA did not fluctuate at any dose. Flow cytometric analysis of splenic cells revealed a dose-dependent decrease of T lymphocyte/B lymphocyte (CD3(+)/B220(+)) ratio from 1.5mg/kg and an elevated CD4(+)helper/CD8(+)cytotoxic T lymphocyte ratio at 6.9 mg/kg. Furthermore, increases of natural killer (NK) activity of splenic lymphocytes against YAC-1 target cells were observed at all doses, while the magnitude of changes was similar between 1.5 and 6.9 mg/kg. At 6.9 mg/kg, the reduction of the ratio of NKR-P1A(+) splenic cells, which is an indicator of NK cells in the spleen, was apparent. As with other previous studies of NIV, decreased body weight was observed from 1.5 mg/kg during the experiment in the present study. In summary, NIV affected immune function in rats after 90-day dietary exposure, the effects being apparent from 0.4 mg/kg judging from the increase of NK activity, although nutritional suppression might have influenced the immunological changes appeared from 1.5mg/kg.
Kubosaki
Atsutaka
A
Division of Microbiology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Aihara
Maki
M
Park
Bong Joo
BJ
Sugiura
Yoshitsugu
Y
Shibutani
Makoto
M
Hirose
Masao
M
Suzuki
Yoshihiko
Y
Takatori
Kosuke
K
Sugita-Konishi
Yoshiko
Y
D000818:Animals; D016516:CD4-CD8 Ratio; D004032:Diet; D005260:Female; D005434:Flow Cytometry; D005670:Fusarium / Q000737:chemistry; D007109:Immunity / Q000187:drug effects*; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D009183:Mycotoxins / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014255:Trichothecenes / Q000633:toxicity*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009183:Mycotoxins; D014255:Trichothecenes; C038405:nivalenol