| Abstract: | Two new 2-substituted thiazolidine-4(R)-carboxylic acids (TCAs), 2-glusosaminal-TCA (GlcNH_2Cys) 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<0.05) increases liver lipid peroxidation to 1.65 and 1.17 times that of the control 4 hr and 24 hr after APAP administration respectively. TCAs treatments can inhibit lipid peroxidation as measured by decreased malondialdehyde (MDA) contents in liver. The histopathological results also further confirm the hepatoprotective effects of TCAs. In conclusion, our data show that TCAs, GlcNAcCys particularly, have hepatoprotective and antioxidant effects. |
