Protective effects of fulvotomentosides on acetaminophen-induced hepatotoxicity.
Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effect of Ful on acetaminophen (AA)-induced hepatotoxicity in mice. Ful pretreatment (75-225 mg.kg-1, sc x 3 d) significantly decreased AA (500 mg.kg-1, ip)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Ful pretreatment (225 mg.kg-1, sc x 3 d) decreased hepatic cytochrome P-450, cytochrome b5, and NADPH-cytochrome c reductase by approximately 15-20%. Microsomes from Ful-pretreated mice, incubated in vitro with AA, produced less AA-glutathione. A 28% increase in urinary excretion of AA-glucuronide was observed in Ful (150 mg.kg-1, sc x 3 d) pretreated mice. Ful pretreatment had no influence on liver UDP-glucuronic acid concentration, but increased hepatic glucuronyltransferase activity towards AA. In summary, Ful pretreatment protects against AA-induced hepatotoxicity. One of the mechanisms for this protection appears to be the decreased AA toxic activation via P-450, as well as increased detoxication via glucuronidation of AA.
Liu
Y P
YP
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
Liu
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J
Jia
X S
XS
Mao
Q
Q
Madhu
C
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Klaassen
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CD
D000082:Acetaminophen / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000652:urine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000517:prevention & control*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D008658:Inactivation, Metabolic; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012503:Saponins; C061620:fulvotomentoside A; D000082:Acetaminophen; D009828:Oleanolic Acid; C037386:acetaminophen glucuronide; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase