TY - JOUR
T1 - Maintenance of hepatic glutathione homeostasis and prevention of acetaminophen-induced cataract in mice by L-cysteine prodrugs
AU - Rathbun, William B.
AU - Killen, Christina E.
AU - Holleschau, Ann M.
AU - Nagasawa, Herbert T.
PY - 1996/5/3
Y1 - 1996/5/3
N2 - Administration of acetaminophen (ACP, 3.0 mmol/kg, i.p.) to β-naphthoflavone-induced C57 BL/6 mice led to the formation of bilateral cataracts with 8 hr with a 71% incidence. The hepatic glutathione (GSH) levels were reduced 99% and lenticular GSH levels reduced 42% in cataractous mice. Cataract formation was completely prevented by the co-administration 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 totalling 4.5 mmol/kg. 2-Oxo-L-thiazolidine-4-carboxylic acid (OTCA) was nearly equipotent, yielding only one cataract in 16 mice, but D-ribose-L-cysteine (Ribcys, 5/16) and N-acetyl-L-cysteine (NAC, 9/14) were much less effective. Hepatic and lenticular GSH were maintained at near normal levels by MTCA, PTCA and OTCA. These results suggest that maintenance of adequate cellular GSH levels in the presence of ACP protects against cataract induction.
AB - Administration of acetaminophen (ACP, 3.0 mmol/kg, i.p.) to β-naphthoflavone-induced C57 BL/6 mice led to the formation of bilateral cataracts with 8 hr with a 71% incidence. The hepatic glutathione (GSH) levels were reduced 99% and lenticular GSH levels reduced 42% in cataractous mice. Cataract formation was completely prevented by the co-administration 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 totalling 4.5 mmol/kg. 2-Oxo-L-thiazolidine-4-carboxylic acid (OTCA) was nearly equipotent, yielding only one cataract in 16 mice, but D-ribose-L-cysteine (Ribcys, 5/16) and N-acetyl-L-cysteine (NAC, 9/14) were much less effective. Hepatic and lenticular GSH were maintained at near normal levels by MTCA, PTCA and OTCA. These results suggest that maintenance of adequate cellular GSH levels in the presence of ACP protects against cataract induction.
KW - acetaminophen
KW - cataracts
KW - glutathione
KW - L-cysteine prodrugs
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U2 - 10.1016/0006-2952(96)00144-X
DO - 10.1016/0006-2952(96)00144-X
M3 - Article
C2 - 8645331
AN - SCOPUS:0029969554
SN - 0006-2952
VL - 51
SP - 1111
EP - 1116
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 9
ER -