Open AccessDifferent effects of nine clausenamide ennatiomers on liver glutathione biosynthesis and glutathione S‐transferase activity in mice
Author(s) -
WU Yuqun,
LIU Lide,
WEI Hualing,
LIU Gengtao
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00348.x
Subject(s) - glutathione , glutathione s transferase , transferase , biosynthesis , glutathione transferase , biology , liver enzyme , biochemistry , endocrinology , medicine , chemistry , enzyme
Aim: To study the effects of nine synthetic clausenamide with different stereo structures on liver glutathione (GSH) biosynthesis and glutathione S‐transferase (GST) activity in mice. Methods: The nine test compounds were racemic mixtures and their ennatiomers of clausenamide, neoclausenamide and epineoclausenamide. Mice were administered clausenamide 250 mg/kgonce daily for 3 consecutive days, ig, and were killed 24 h after the last dosing. The mouse liver cytosol GSH and GST were determined with related biochemical methods. Results: Nine clausenamides exhibited different effects on liver GSH and GST. Of nine clausenamides, only (+) and (±)clausenamide markedly increased liver cytosol GSH content. The mechanism of increasing liver GSH content of (+)clausenamide is mainly due to stimulating the key limiting enzyme γ‐glutamylcysteine synthetase (γ‐GCS) activity for GSH biosynthesis. The other test clausenamides had no such effect on liver GSH. All of the nine clausenamides induced a significant increase of GST activity. Conclusion: The effects of clausenamide ennatiomers on liver GST and GSH varied with the alterations of their spatial structures. (+)Clausena‐mide stimulated liver GSH biosynthesis through enhancing γ‐GCS activity.