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Two new 2-substituted thiazolidine-4(R)-carboxylic acids (TCAs), 2-glusosaminal-TCA (GlcNH2Cys) and 2-N-acetyl-glucosaminal-TCA (GlcNAcCys), were synthesized. Their protective effects against liver toxicity induced by acetaminophen (APAP) were investigated in a mice model. The results demonstrate that administration of TCAs (i.p., 800 mg/kg) 30 min after APAP challenge efficiently decrease ALT, AST, and LDH levels in liver. GlcNAcCys shows the best protective effects, decreasing ALT, AST and LDH levels to 63%, 18.4% and 37% of the APAP group respectively. Comparison with the control showed that APAP greatly decreases total sulfhydryl (T-SH) levels (43%), non-protein bound sulfhydryl (NP-SH) levels (50%) and total antioxidative capabilities (57%) in the liver 24 hr after challenge. TCAs treatments 30 min after APAP challenge significantly elevate sulfhydryl levels and total antioxidative capabilities. APAP administration also markedly (P