Mario V. Torrielli

Behaviour of lipoperoxidation in rat liver during orotic acid treatment.

Abstract The non-enzymatic production of malonyldialdehyde by liver homogenate is enhanced during the earliest stages of dietary administration of orotic acid. These alterations are prevented by injecting either DPPD or adenine. However, the ultraviolet absorption spectrum of total lipids and the concentration of plyunsaturated fatty acids of phospholipids of the mitochondrial and microsomal fractions were unchanged during the steatogenic treatment. These findings are not consistent with the hypothesis which envisions a direct attack by lipoperoxidation, induced by the metabolism of orotic acid, on the unsaturated lipids of the cell membranes.

Further observation on the effects of 3-methylcholanthrene and phenobarbital on carbon tetrachloride hepatotoxicity.

Abstract The behavior of PB and 3-MC, inducers of the enzymatic chain of the hepatic DMES, was studied in relation to their effects upon CCl 4 -hepatotoxicity. The secretion of triglycerides from liver into the plasma compartment was inhibited in CCl 4 -poisoned rats, as well, in the animals pretreated with PB and 3-MC. The lipid peroxidative phenomena (diene conjugation absorption), evidenced in rats intoxicated with the halogenated hydrocarbon, were enhanced by pretreatment with PB, while 3-MC, in this respect, had no effect. At 60 min after poisoning, the severe polysomal damage was not modified either by 3-MC or PB, while the recovery process (25 hr of intoxication) was at its highest in rats treated with CCl 4 alone, slower in 3-MC or PB pretreated rats. Cell necrosis, as measured by S-GOT and S-GPT, was protected in CCl 4 -intoxicated rats by pretreating the animals with 3-MC.

Effect of a cholesterol-rich diet on cholesterol content and phagocytic activity of rat macrophages

Treatment for 11–13 weeks with a cholesterol-rich diet induced increases in free and esterified serum cholesterol. There was also an increase in free cholesterol of peritoneal macrophages. A 2.2 times rise in the cholesterol to phospholipid ratio of plasma membranes occurred in cholesterol-enriched macrophages. No changes were observed in phagolysosomes. Cholesterol-enriched macrophages showed a 35.8% inhibition of latex particles phagocytosis. When lipid droplets were substituted for latex the inhibition was 81.7%.

Effect of drug pretreatment on CBrCl3-induced liver injury☆

Abstract This study deals with the interaction of administered drugs with CBrCl3- induced toxicity. In vivo lipoperoxidation, fatty infiltration and necrosis of the liver were followed after poisoning with CBrCl3 in animals pretreated with phenobarbital, 2-diethylaminoethyl-2,2-diphenylvalerate (SKF-525A) or N, N′-diphenyl-p-phenylanediamine (DPPD). Double-bond shifting in liver microsomal lipids appeared to be enhanced by administration of barbiturate, whereas SKF-525A and DPPD lowered the extent of the peroxidative attack. Both hepatic triglyceride accumulation and leakage of liver enzymes (alanine aminotransferase [GPT] and aspartate aminotransferase [GOT]) into the plasma behaved similarly in the animals dosed orally with CBrCl3 (10 μl per 100 g body wt.). Lethality by CBrCl3 was reduced in rats pretreated with a small dose of CCl4 (25 μl per 100 g body wt.) which protects against an otherwise lethal dose of CCl4. In our opinion, this phenomenon indicates that the lethal effect of CBrCl3 also depends on the actual efficiency of the drug-metabolizing enzyme systems in the liver.

Interference of DPPD with hepatic drug metabolizing enzyme system

Summary The direct effects by in vivo administered DPPD on hepatic microsomal enzyme activities have been investigated with the aim to elucidate the mechanism of protection by this compound against toxic liver injuries. The efficiency of hepatic drug metabolizing system has been evaluated both in vitro and in vivo . Furthermore, liver necrosis (serum GPT activity) was estimated in rats poisoned with carbon tetrachloride after DPPD treatment. The administration of DPPD lowers down the activity of liver aminopyrine demethylase and enlarges the hexobarbital sleeping time. CCl 4 alone inhibits the microsomal enzymes, while a preliminary treatment with DPPD fails in preventing but renders more remarkable the block induced by the halogenoalkane. However, the antioxidant completely protects against liver necrosis in CCl 4 -poisoned rats. These findings support the hypothesis that the biological activities of DPPD can be mediated also by inhibition of drug metabolizing enzymes bound to the endoplasmic reticulum.