MAINTENANCE OF HEPATIC GLUTATHIONE HOMEOSTASIS AND PREVENTION OF ACETAMINOPHEN-INDUCED CATARACT IN MICE BY L-CYSTEINE PRODRUGS

Administration of acetaminophen (ACP, 3.0 mmol/kg, i.p.) to beta-napht hoflavone-induced C57 BL/6 mice led to the formation of bilateral cata racts within 8 hr with a 71% incidence. The hepatic glutathione (GSH) levels were reduced 99% and lenticular GSM levels reduced 42% in catar actous mice. Cataract formation was completely prevented by the co-adm inistration of the L-cysteine prodrugs 2(R,S)-methylthiazolidine-4(R)- carboxylic acid (MTCA) and 2(R,S)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA) in two divided i.p. doses totaling 4.5 mmol/kg. 2-Oxo-L-t hiazolidine-4-carboxylic acid (OTCA) was nearly equipotent, yielding o nly one cataract in 16 mice, but D-ribose-L-cysteine (RibCys, 5/16) an d N-acetyl-L-cysteine (NAC, 9/14) were much less effective. Hepatic an d lenticular GSH were maintained at near normal levels by MTCA, PTCA a nd OTCA. These results suggest that maintenance of adequate cellular G SH levels in the presence of ACP protects against cataract induction.