fulvotomentoside-a and Chemical-and-Drug-Induced-Liver-Injury

Fulvotomentoside alpha-hederin (H) and sapindoside B (S) are two components of the fulvotomentosides reported to decrease the toxicity of a number of hepatotoxins in mice. We studied the effects of the mixture of alpha-hederin and sapindoside B (HS) on paracetamol (Par)-induced liver injury. HS (20 mg.kg-1 sc twice) was shown to decrease the mortality produced by Par. The liver injury produced by Par was remarkably decreased as indicated by decrease of sGPT and by histopathological examination. Additionally, HS mitigated the hepatic GSH depletion caused by Par. Par excretion into urine was increased following HS.

Topics: Acetaminophen; Animals; Chemical and Drug Induced Liver Injury; Drugs, Chinese Herbal; Glutathione; Liver; Liver Diseases; Male; Mice; Oleanolic Acid; Saponins

Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effects of Ful on cadmium (CdCl2)-induced acute liver injury in mice. Ful pretreatment (150 mg.kg-1, sc x 3 d) remarkably decreased CdCl2 (3.7 mg Cd.kg-1, iv)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Distribution of Cd to 12 organs and hepatic subcellular fractions was determined 2 h after Cd challenge. Ful pretreatment did not produce a marked shift in the distribution of Cd to various organs, but markedly altered the hepatic subcellular distribution of Cd, with more Cd bound to metallothionein (MT) in the cytosol, less in the nuclear, mitochondrial, and microsomal fractions. Ful pretreatment produced a dose-dependent increase in hepatic MT as determined by the Cd.hemoglobin assay. In conclusion, Ful protected against Cd hepatotoxicity by inducing MT, which binds Cd in the cytosol and lowers the amount of Cd available to other critical organelles and proteins.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cadmium Poisoning; Chemical and Drug Induced Liver Injury; Liver; Male; Metallothionein; Mice; Oleanolic Acid; Saponins; Tissue Distribution

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.

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Glucuronosyltransferase; Inactivation, Metabolic; Male; Mice; Microsomes, Liver; Oleanolic Acid; Saponins