Time course of protection by N,N'-Diphenyl-p-phenylendiamine (DPPD) against carbon tetrachloride hepatotoxicity
- 29 Downloads
A preliminary treatment with DPPD (N,N'-diphenyl-p-phenylendiamine) prevents liver fatty infiltration early after carbon tetrachloride poisoning. Double bond shifting in microsomal lipids appears to be depressed 30 minutes after intoxication. A more active protection takes place when low doses of CCl4 are given (25 μl per 100 g body weight) than after a large dose of the poison (250 μl). In later stages of the halogenoalkane challenge, both triglyceride accumulation and lipid peroxidation take place despite of the antioxidant treatment. However, they are less severe and more transient than in unprotected animals. Similarly, liver necrosis, as evidenced by changes in serum activity of alanine aminotransferase appears, to be prevented by DPPD. This compound does not interfere with the hepatic metabolism of carbon tetrachloride, as suggested by the findings of14C binding to liver lipids and exhalation of radioactive CO2 after administration of14CCl4.
Moreover, pretreatment with antioxidant partially inhibits the in vitro demethylation of aminopyrine by liver microsomes and significantly potentiates the hypnotic effect of hexobarbital. Further, DPPD, when injected along with phenobarbital, blocks the barbiturate stimulation of microsomal enzymes. A combined dosing with both DPPD and CCl4 causes a more severe inhibition of demethylase activity and hexobarbital metabolism.
Our results indicate that DPPD can act as an inhibitor of the enzymes bound to the endoplasmic reticulum, beside its antioxidant properties, during CCl4 intoxication.
KeywordsCCl4 Phenobarbital Carbon Tetrachloride Fatty Infiltration Aminopyrine
Unable to display preview. Download preview PDF.
- N. R. Di Luzio andF. Costales,Inhibition of the Ethanol and Carbon Tetrachloride Fatty Liver by Antioxidants, Exp. Mol. Pathol.4, 141 (1965).Google Scholar
- G. Ugazio andM. V. Torielli,Effect of Propyl Gallate on Carbon Tetrachloride Induced Fatty Liver, Biochem. Pharmac.18, 2271 (1969).Google Scholar
- M. U. Dianzani andG. Ugazio,Lipoperoxidation after Carbon Tetrachloride Poisoning in Rats Previously Treated with Antioxidants, Chem.-Biol. Interactions6, 67 (1973).Google Scholar
- M. V. Torrielli andG. Ugazio,Effect of DPPD on the Orotic Acid-Induced Fatty Liver in the Rat, Life Sci.9, 1 (1970).Google Scholar
- M. V. Torrielli, M. U. Dianzani andG. Ugazio,Behaviour of Lipoperoxidation in Rat Liver during Orotic Acid Treatment, Life Sci.10, 99 (1971).Google Scholar
- M. V. Torrielli andG. Ugazio,Biochemical Aspects of the Protective Action of Propyl Gallate on Liver Injury in Rats Poisoned with CCl 4, submitted to Tox. appl. Pharmac.Google Scholar
- S. P. Chiang, C. F. Gessert andO. H. Lowry,Colorimetric Determination of Extracted Lipids. An Adaptation for Microgram Amounts Obtained from Cerumen, Current List of Medical Literature33, Res. Rep. No. 56–113 (1957).Google Scholar
- S. Orrenius,Mechanism of Drug Hydroxylation in Rat Liver Microsomes, J. Cell. Biol.26, 113 (1965).Google Scholar
- K. Fukuzumi andN. Ikeda,Study on the Effect of Antioxidants in the Autoxidation of Methyl non Conjugated Octadecadienoates, J. Am. Oil Chem. Soc.46, 64 (1969).Google Scholar
- G. Ugazio, E. Burdino, A. M. Congiu andM. U. Dianzani,Azione protettiva degli antiossidanti in vitro a diverse temperature, Comm. 7th Int. Symp. Exp. Dermatol. Palermo, 28–30 March 1974.Google Scholar
- E. Gravela, L. Gabriel andG. Ugazio,Protection by Glutathione and Propyl Gallate on the Impaired in vitro Aminoacid Incorporation into Liver Microsomal Protein of CCl 4-Poisoned Rats, Biochem. Pharmac.20, 2065 (1971).Google Scholar
- W. S. Hartroft andE. A. Porta,Present Knowledge of Ceroid Pigment, in:Present Knowledge in Nutrition, 3rd ed. (The Nutrition Foundation Inc., N.Y. 1967), p. 28.Google Scholar
- L. Gabriel, E. Burdino, M. V. Torrielli andG. Ugazio,Interference of DPPD with Hepatic Drug Metabolizing Enzyme System, Pharmac. Res. Commun.6, 127 (1974).Google Scholar