[Protection against paracetamol-induced hepatic damage using total flavonoids of Astragalus].
OBJECTIVE
To study the mechanism of the protection by total flavonoids of Astragalus protection against paracetamol-induced hepatic damage.


METHODS
Analysing paracetamol and its metabolites in mice urine by HPLC and studying the mechanism of anti-damage induced by paracetamol using experiment module of pentobarbital-induced sleeping time.


RESULTS
Administration of large doses of paracetamol to C57BL/6J mice produced significant hepatic injury with marked elevation in serum ALT activity and severe hepatocellular necrosis. TFA showed a good protective capability against paracetamol-induced hepatic injury. TFA had no marked effect on paracetamol and its metabolites except for the mercapturate-conjugate. The concentration of mercapturate change decreased with increasing TFA dose. TFA had no effect on the pentobarbital metabolites (P > 0.05). However, paracetamol (400 mg.kg-1) prolonged the sleeping time (by 110 min relative to the controls, P < 0.001). The TFA (P < 0.005) caused significant reduction in paracetamol-prolonged pentobarbital-induced sleep.


CONCLUSIONS
The mechanism of TFA's protective effect against the paracetamol-induced damage may be related to the inhibition of some metabolism progress of paracetamol and the reduction of the toxicity metabolite such as mercapturate-conjugate.
Wang
D Q
DQ
Division of Clinical Pharmacology, Department of Medicine and Therapeutics, Department of Biochemistry, PLA General Hospital, Beijing 100853.
Critchley
J A
JA
Ding
B G
BG
Ma
Y Q
YQ
Zhao
H L
HL
Thomas
G N
GN
Tian
Y P
YP
Tomlinson
B
B
Critchley
L A
LA
Edward
J A
JA
D000082:Acetaminophen / Q000378:metabolism; D000818:Animals; D027885:Astragalus propinquus / Q000737:chemistry*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010946:Plants, Medicinal / Q000737:chemistry*; D020011:Protective Agents / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects
D005419:Flavonoids; D020011:Protective Agents; D000082:Acetaminophen