1. The ability of ascorbic acid to protect from prooxidant-induced tox
ic injury was investigated in isolated, intact rat hepatocytes, whose
ascorbic acid content had been restored by means of exogenous suppleme
ntation. 2. Ascorbate-supplemented and ascorbate-non-supplemented cell
s in suspension were treated with a series of different prooxidants (a
llyl alcohol, diethyl maleate, carbon tetrachloride, menadione), and t
he development of lipid peroxidation and cell injury was evaluated. 3.
With allyl alcohol and diethyl maleate, ascorbic acid was able to pro
tect cells from both lipid peroxidation and cell injury. The same prot
ection was offered by ascorbate also in hepatocytes obtained from vita
min E-deficient animals. 4. With carbon tetrachloride, ascorbate suppl
ementation did not affect the initial steps of lipid peroxidation, but
nevertheless provided a marked protection against lipid peroxidation
and cell injury at later times of incubation. The protection was unaff
ected by the vitamin E content of cells. 5. With menadione, a toxin wh
ich does not induce lipid peroxidation, ascorbic acid did not protect
cells against injury. 6. It is concluded that ascorbic acid can act as
an efficient antioxidant in isolated rat liver cells, with protection
against cell injury. The antioxidant effect appears primarily to invo
lve membrane lipids, and can be independent from the cellular content
of vitamin E, thus suggesting that ascorbic acid can play a direct and
independent role in the intact cell, in addition to its synergistic i
nteraction with vitamin E described in other models.