F. Atroshi et al., Fumonisin B-1-induced DNA damage in rat liver and spleen: Effects of pretreatment with coenzyme Q(10), L-carnitine, alpha-tocopherol and selenium, PHARMAC RES, 40(6), 1999, pp. 459-467
Active oxygen radical species are reported to cause organ damage. This stud
y was designed to determine whether oxidative stress contributed to the ini
tiation or progression of hepatic and splenic cell DNA damage induced by fu
monisin B-1 (FB1) in rats. Another aim was to investigate the protective ef
fects of the antioxidants coenzyme Q(10) (CoQ(10)), L-carnitine, vitamin E
(alpha-tocopherol) and selenium against DNA damage in the liver and spleen
of rats treated with FB1. Fasted rats were injected intravenously with a si
ngle dose of fumonisin B-1 at 1.55 mg kg(-1) body wt. into the tail vein. T
reatment with FB, led to splenic and hepatic DNA fragmentation in 85% of th
e test animals. DNA fragmentation was investigated as a critical event in t
oxic cell death by testing total Ca2+ in liver. FB, administration caused t
otal Ca2+ in liver to increase within 4 h (204% of control). Measurement of
liver enzyme activities showed an increase in aspartate aminotransferase (
ASAT) and alanine aminotransferase (ALAT). FB1 also markedly decreased sple
nic and hepatic glutathione (GSH) levels. Pretreatment with CoQ(10) (30 mg
CoQ(10) kg(-1) diet) together with L-carnitine (2.8 mg carnitine kg(-1) die
t), alpha-tocopherol (30 IU vitamin E kg(-1) diet) and selenium (1 mg selen
ium as sodium selenite kg(-1) diet), decreased DNA damage and the activitie
s of Ca2+, ASAT and ALAT in the liver. On the other hand, the level of GSH
was slightly increased. The CoQ(10) alone did not significantly protect aga
inst toxic cell death and glutathione depletion caused by FB1. Oxidative da
mage caused by FB1 may be one of the underlining mechanisms of FB1-induced
cell injury and DNA damage. (C) 1999 Academic Press.