Porphyrins such as
protoporphyrin IX (PP IX) and
uroporphyrin I (UP I) can be phototoxic to human cells. To study the protective ability of
antioxidants (
beta-carotene,
lycopene,
ascorbic acid and
alpha-tocopherol), against such
porphyrin phototoxicity, membrane destruction experiments (Jurkat cells) and human cell cultures (fibroblasts) were performed. Both
beta-carotene and
lycopene and also the combination of
beta-carotene,
ascorbic acid and
alpha-tocopherol offered cell protection against PP IX
phototoxicity. Investigations of both cell membrane protection and of cell growth showed differences in terms of the protection afforded by the
anti-oxidants. Thus, for PP IX,
carotenoids alone, and in combination with
ascorbic acid and
alpha-tocopherol, showed higher protection factors in general than UP I. However, for membrane protection there was significant protection against UP I by the combination of
beta-carotene,
ascorbic acid and
alpha-tocopherol but not by any of these
anti-oxidants alone. The membrane protection against PP IX by
beta-carotene, and especially
lycopene, is significant presumably because of the high lipophilicity of all these molecules. However, the hydrophilic UP I will cause
phototoxicity mainly via H(2)O(2), radical or
singlet oxygen production in the aqueous phase, and these reactive species may be generated some distance from the cell membrane. This may lead to the little or no protection observed for UP I by the individual
antioxidants. Nevertheless, a combination of
beta-carotene,
ascorbic acid and
alpha-tocopherol offers membrane protection against the
phototoxicity of both
porphyrins. This is believed to occur as a result of synergistic processes. Our results suggest that the treatment of
porphyria cutanea tarda and
erythropoietic protoporphyria may be improved by the use of a combination of the
antioxidants studied.