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[Protection against paracetamol-induced hepatic damage using total flavonoids of Astragalus]
D Q Wang1, J A Critchley, B G Ding
1Division of Clinical Pharmacology, Department of Medicine and Therapeutics, Department of Biochemistry, PLA General Hospital, Beijing 100853.
Objective:
To study the mechanism of the protection by total flavonoids of Astragalus protection against paracetamol-induced hepatic damage.
Method:
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.
Result:
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.