Rapid-onset
cataracts were induced in SPF C57 bl/6 mice by intraperitoneal administration of
naphthalene following
cytochrome P-450 isozyme induction with
phenobarbital. Several
L-cysteine prodrugs with masked sulfhydryl groups in the form of thiazolidine-4-carboxylic
acids, as well as
N-acetyl-L-cysteine, N,S-bis-acetyl-
L-cysteine and
glutathione ethyl ester, were evaluated for their ability to maintain hepatic and lenticular
glutathione at near-normal levels and to prevent
naphthalene-induced
cataract formation. Each
prodrug was administered at three specified times to a cumulative total of 1.5 mole equivalents of the single dose of
naphthalene. Three
L-cysteine prodrugs delayed but did not prevent
cataract formation in 40-60% of the mice over a 72-hr period, while eight of the 13 compounds produced
cataract yields similar to the
naphthalene control animals, i.e. 83% in 72 hr. However, two
L-cysteine prodrugs, 2(R,S)-methylthiazolidine-4(R)-carboxylic
acid (
MTCA) and 2(R,S)-n-propylthiazolidine-4(R)-carboxylic
acid (PTCA), prevented
cataract formation in 20 of 21 and 12 of 12 mice, respectively, and maintained hepatic
reduced glutathione levels at 82% and 51% of untreated controls. In contrast,
glutathione was depressed to 3% of the normal value in those animals treated with
naphthalene alone. Lenticular
glutathione values were depressed, albeit minimally, in all
naphthalene-treated mice regardless of administration of either
MTCA or PTCA. The mice protected with either
MTCA or PTCA showed no visible effects of
naphthalene toxicity or
lens opacities at any time. It can be concluded that these
L-cysteine prodrugs were effective in preventing
naphthalene-induced
cataract and maintaining near-normal hepatic
glutathione levels.