Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice

Lee, KJ You, HJ Park, SJ Kim, YS Chung, YC Jeong, TC Jeong, HG

Kj. Lee et al., Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice, CANCER LETT, 174(1), 2001, pp. 73-81

36

INGLESE

Article

Onconogenesis & Cancer Research

CANCER LETTERS

0304-3835 → ACNP

174

1

2001

73 - 81

ISI

0304-3835(200112)174:1<73:HEOPGO>2.0.ZU;2-Z

The protective effects of an aqueous extract from the roots of Platycodon g randiforum A. DC (Campanulaceae), Changkil (CK), on acetaminophen (APAP)-in duced hepatotoxicities and the possible protective mechanisms involved were investigated in mice. Pretreatment with CK prior to the administration of APAP significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. APAP-induced hepatotoxicity was also essentially p revented as evidenced by liver histopathology. Hepatic glutathione levels a nd glutathione-S-transferase activities were not affected by treatment with CK alone, but pretreatment with CK protected the APAP-induced depletion of hepatic glutathione levels. The effects of CK on cytochrome P450 (P450) 1A 2 and 2E1, the major isozymes involved in APAP bioactivation, were investig ated. In microsomal incubations, CK effectively inhibited P450 1A2-dependen t methoxyresorufin O-deethylase activities and the P450 2E1-dependent p-nit rophenol and aniline hydroxylase. The results suggest that the protective e ffects of CK against the APAP-induced hepatotoxicity may, at least in part, be due to its ability to block P450-mediated APAP bioactivation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.