Different effects of nine clausenamide ennatiomers on liver glutathione biosynthesis and glutathione S-transferase activity in mice.
OBJECTIVE
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/kg once 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 gamma-glutamylcysteine synthetase (gamma-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.


CONCLUSIONS
The effects of clausenamide ennatiomers on liver GST and GSH varied with the alterations of their spatial structures. (+)Clausenamide stimulated liver GSH biosynthesis through enhancing gamma-GCS activity.
Wu
Yu-Qun Wu
YQ
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
Liu
Li-De
LD
Wei
Hua-Ling
HL
Liu
Geng-Tao
GT
D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017705:Lignans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007769:Lactams; D017705:Lignans; C053048:clausenamide; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione