Time course of protection by N,N'-Diphenyl-p-phenylendiamine (DPPD) against carbon tetrachloride hepatotoxicity
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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
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