isosafrole has been researched along with Chemical-and-Drug-Induced-Liver-Injury* in 2 studies
2 other study(ies) available for isosafrole and Chemical-and-Drug-Induced-Liver-Injury
| Article | Year |
|---|---|
The prevention of ferric nitrilotriacetate-induced nephro- and hepatotoxicity by methylenedioxybenzene antioxidants.
Previously it was shown that methylenedioxybenzenes (MDBs), particularly isosafrole, were highly effective at preventing CCl4-induced liver necrosis in vivo (Z.S. Zhao, P.J. O'Brien, The prevention of CCl4-induced liver necrosis in mice by naturally occurring methylenedioxybenzenes, Toxicol. Appl. Pharmacol., 140 (1996) 411-421), probably as a result of forming metabolic intermediate complexes with cytochrome P450. In the following it was shown that pretreatment of mice with isosafrole also completely prevented ferric nitrilotriacetate (FeNTA)-induced renal necrosis and lipid peroxidation, even though metabolic activation by cytochrome P450 is not involved. The naturally occurring or synthetic MDBs that prevented CCl4 hepatotoxicity also prevented hepatocyte lipid peroxidation. induced by FeNTA, but other cytochrome P450 inhibitors were ineffective. These compounds, in decreasing order of antioxidant effectiveness, were sesamol, 4-t-butyl-methylenedioxybenzene, isosafrole, piperonyl butoxide and 4-bromo-methylenedioxybenzene and safrole, whereas, benzodioxole, 3,4-(methylenedioxy)-toluene and 1,2-(methylenedioxy)-4-nitrobenzene were ineffective. Pre-incubating the hepatocytes with P450 inhibitors decreased the protective effects of isosafrole, suggesting that the catecholic metabolites of MDBs were responsible for the antioxidant activity. A greater inhibition of FeNTA-induced lipid peroxidation by catecholic metabolites was observed. Since cytochrome P450 did not participate in FeNTA-induced hepatocyte or microsomal lipid peroxidation, it is likely that the antioxidant properties of MDBs or their catecholic metabolites also contribute to their in vivo protection against CCl4 or FeNTA-induced hepato- or nephrotoxicity. Topics: Animals; Antioxidants; Carcinogens; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Dioxoles; Ferric Compounds; Kidney; Kidney Diseases; Lipid Peroxidation; Liver; Liver Diseases; Male; Mice; Microsomes, Liver; Necrosis; Nitrilotriacetic Acid; Rats; Rats, Sprague-Dawley; Safrole | 1997 |
Polycyclic aromatic hydrocarbons cause hepatic porphyria in iron-loaded C57BL/10 mice: comparison of uroporphyrinogen decarboxylase inhibition with induction of alkoxyphenoxazone dealkylations.
Multiple doses of beta-naphthoflavone to iron-loaded C57BL/10ScSn mice for 6 weeks caused inhibition of hepatic uroporphyrinogen decarboxylase and a porphyria indistinguishable from that previously only reported for polyhalogenated aromatic chemicals. beta-Naphthoflavone and other polycyclic aromatic hydrocarbon inducers of cytochrome P1-450-mediated ethoxyphenoxazone deethylation (ethoxyresorufin deethylase), benzo[a]pyrene, benz[a]anthracene, dibenz[ah]anthracene, 3-methylcholanthrene and alpha-naphthoflavone, also gave porphyria when fed. Isosafrole was inactive but by both methods phenobarbital produced a small but significant inhibition of the decarboxylase. The results demonstrate a toxic action of polycyclic aromatic hydrocarbons which probably does not involve reactive metabolites. Topics: Animals; Benz(a)Anthracenes; Benzo(a)pyrene; Benzoflavones; beta-Naphthoflavone; Carboxy-Lyases; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System; Enzyme Induction; Iron; Male; Mice; Mice, Inbred C57BL; Oxidoreductases; Phenobarbital; Polycyclic Compounds; Porphyrias; Safrole; Uroporphyrinogen Decarboxylase | 1987 |