EFFECT OF POLYSACCHARIDE PEPTIDE (PSP) ON GLUTATHIONE AND PROTECTION AGAINST PARACETAMOL-INDUCED HEPATOTOXICITY IN THE RAT

The protective effects of polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, on paracetamol-induced hepatotoxicity was i nvestigated in this study. The effect of PSP on hepatic glutathione st atus was also studied. PSP (300 mg/kg, i.p.) caused a 40% depletion of hepatic reduced glutathione (GSH) with a concomitant 50% increase in oxidized glutathione (GSSG), thus producing a 3-fold increase in the G SSG/GSH ratio. The PSP-induced GSH depletion itself had no hepatotoxic effects. PSP-protected against paracetamol-induced hepatotoxicity by decreasing the paracetamol-induced elevation of serum glutamic-pyruvic transaminase (SGPT) activity from 511 +/- 71 U/ml to 187 +/- 58 U/ml( controls without paracetamol 105 +/- 4 U/ml) and serum glutamic-oxaloa cetic transaminase (SGOT) activity from 462 +/- 63 to 152 +/- 48 U/ml (controls without paracetamol 54 +/- 6 U/ml). PSP did not reverse the depletion of total glutathione (GSH + GSSG) by the toxic dose of parac etamol. The GSSG/GSH ratio, which is a measure of oxidative stress, wa s significantly (p <0.05) decreased when PSP was coadministered with p aracetamol. PSP dose-dependently decreased the covalent binding of[C-1 4]-paracetamol to microsomal proteins in vitro. When PSP was given to rats subchronically for 7 days (300 mg/kg/day, i.p.), the subsequent m icrosomes obtained also showed a 25% decrease in covalent binding to [ C-14]-paracetamol, suggesting that PSP interacted with the microsomal proteins rather than the chemically reactive metabolite of paracetamol . The changes in the binding affinity and capacity of the microsomal p roteins by PSP may be related to its ability to alter the redox potent ial as indicated by the effects of PSP on the GSSG/GSH status.