These studies were conducted to investigate whether ascorbic acid prot
ected guinea pigs from aflatoxin B1 (AFB(1)) toxicity. Young guinea pi
gs, fed either 0 (AA) or 25 mg (25 AA) or gavaged 300 mg ascorbic acid
(300 AA) per day for 21 days, were gavaged with the LD50 dose of AFB(
1) on the 22nd day. Seven out of 10 animals in the AA group died withi
n 72 hr of AFB(1) administration. The livers of the animals showed reg
ional massive necrosis and multilobular degeneration. There was no mor
tality in the 25 AA group. Their livers, however, showed changes simil
ar to those seen in AA group. Serum alanine amino transferase (ALAT) a
nd aspartate amino transferase (ASAT) levels were elevated. There was
neither mortality nor pathological changes in livers in the 300 AA gro
up. Their ALAT and ASAT levels were unaffected. in vitro production of
AFM(1) by liver microsomes tended to be higher than that in the other
two groups. Three animals saved from the 300 AA group and continued w
ith their supplementation were administered a second, intraperitoneal
(ip) LD50 dose of AFB(1) 1 month after the first AFB(1) dose. One anim
al died. Livers of the animals showed centrilobular degeneration and m
oderate necrosis in scattered hepatocytes. Liver microsomal cytochrome
P450 and cytosolic glutathione S-transferase (GST) levels and AFM(1)
production were drastically reduced. ALAT and ASAT activities were rai
sed. The results indicated that intake of 300 mg of ascorbic acid almo
st protected the animals from acute toxicity of AFB(1) when given by g
avage, but not When administered as a second dose ip. (C) 1997 Academi
c Press.