Hepatoprotective and hepatotoxic activities of sophoradiol analogs on rat primary liver cell cultures

Citation
J. Kinjo et al., Hepatoprotective and hepatotoxic activities of sophoradiol analogs on rat primary liver cell cultures, BIOL PHAR B, 23(9), 2000, pp. 1118-1121
Citations number
24
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOLOGICAL & PHARMACEUTICAL BULLETIN
ISSN journal
09186158 → ACNP
Volume
23
Issue
9
Year of publication
2000
Pages
1118 - 1121
Database
ISI
SICI code
0918-6158(200009)23:9<1118:HAHAOS>2.0.ZU;2-V
Abstract
As a part of our studies of hepatoprotective drugs,,ve prepared kaikasaponi n I (2), sophoradiol monoglucuronide (SoMG, 3) and sophoradiol (4) from kai kasaponin III (1). We examined the hepatoprotective effects of these analog s, using immunologically-induced liver injury in primary cultured rat hepat ocytes and found that compound 1 was more effective than soyasaponin I (1a) while 2 was more effective than 1. On the other hand, 3 was less effective than 2 at 30-200 mu M. Further, compound 3 was strongly cytotoxic at 500 m u M while 4 exhibited hepatoprotective activity at the same dose, although less potent. When the cytotoxicity toward hepatocytes of these analogs was tested, only 3 was cytotoxic at doses of 200 and 500 mu M. This is the firs t example of an oleanene glucuronide (OG) which is cytotoxic toward hepatoc ytes. Compound 3 exhibited hepatoprotective activity at 200 mu M, while it was also cytotoxic at the same dose without antiserum. Therefore, the hepat oprotective activity of OG represents a balance between a hepatoprotective action and its cytotoxicity toward hepatocytes.