[Susceptibility of the liver to lipid peroxidation after treatment with paracetamol]. / Suscettibilita' del fegato alla perossidazione pipidica dopo trattamento con paracetamolo.

Intoxication of rats with paracetamol (2.0 g/kg, b. wt.,os) is not followed by peroxidative decomposition of liver microsomal lipids "in vivo" but seems to interfere with ATPase and 5'-Nucleotidase activity in isolated plasmamembranes. Treatment with reduced glutathione, cys=teine and 2. mercaptopropionylglycine results in partial protection against liver injury provoked by the toxin. However, these sulphydryl compounds are not able to prevent the fall of liver GSH content occurring after paracetamol.

[Influence of pretreatment with carbon tetrachloride on paracetamol-induced hepatotoxicity]. / Influenza del pretrattamento con tetracloruro di carbonio sull'epatotossicita' del paracetamolo.

The influence of preventive treatment with a low dose of carbon tetrachloride on paracetamol-induced hepatotoxicity was evaluated in the rat. The haloalkane was given intraperitoneally (200 microliter/kg) 48 hours prior to paracetamol (PRCT; 2000 mg/kg, os). In parallel groups of rats were treated with CCl4 or PRCT alone. Twelve hours after paracetamol all the animals were killed. Liver damage was determined by evaluating total lipid and triglyceride accumulation in hepatic tissue and the serum activity of alanine-amino transferase (S.GPT). In addition, both the hepatic concentration of reduced glutathione (GSH) and the production "in vitro" of TBA-reacting compounds by liver homogenate were assayed. The results obtained indicate CCl4 "per se" induces a significant triglyceride accumulation but does not influence either the hepatic GSH level or the leakage of GPT into the blood stream. In addition, the haloalkane does not stimulate the production of TBA-reacting substances by hepatic tissue. Paracetamol, alone, produces a slight increase of hepatic triglycerides while induces a significant (+ 108%) enhancement of S.GPT activity. The drug is also able to stimulate the lipid peroxidation "in vitro", whereas provokes a marked decrease of GSH in liver tissue. Combined treatment with the two poisons results in a minor alteration of hepatocyte function as shown by the lack of GPT in serum and by the reduced fall of hepatic GSH as well as by a decreased production of TBA-reacting compounds. In our opinion, CCl4 partially protects against paracetamol-induced liver injury by interacting with enzymes which are responsible for the biotransformation of PRCT to a reactive arylating species that bind to cell molecules.

[Liver damage after paracetamol and carbon tetrachloride administration]. / Osservazioni sperimentali sul danno epatico conseguente alla somministrazione di paracetamolo e tetracloruro di carbonio.

Preliminary data on the liver damage following combined treatment with paracetamol and carbon tetrachloride in the rat are reported. Administration of a single dose of paracetamol (2000 mg/kg, os) was followed after 1 hour by an intraperitoneal injection of CCl4 (1.0 ml/Kg). Experiments in parallel were performed in rat given paracetamol or CCl4 alone. Our results indicate paracetamol induces a drastic decrease of hepatic GSH that appears in relation with a marked production of TBA-reacting compounds in liver tissue, while CCl4 does not modify the hepatic content of GSH and provokes a slight increase of TBA-reacting substances. Preventive treatment with paracetamol of rats intoxicated after 1 hour with carbon tetrachloride results in a partial protection against fatty liver and necrosis following haloalkane poisoning. On the other hand, the combined treatment with both the hepatotoxins was followed by a minor decrease of GSH. These data are discussed in considering a possible interaction of the two chemicals at the site of their activation.

[Relationship between GSH depletion and "in vitro" lipoperoxidative processes in liver of rats intoxicated with paracetamol (author's transl)]. / Rapporto fra la caduta del livello di GSH ed i processi lipoperossidativi "in vitro" nel fegato di ratti intossicati con paracetamol.

The time-course of reduced glutathione depletion in total liver homogenates from rats intoxicated with a single toxic dose of paracetamol (2000 mg/kg,os) was determined in parallel with the rate of production of TBA-reacting compounds. In addition, liver damage, as assayed by evaluation of leakage into blood stream of alanine-amino transferase and of the concentration of total hepatic lipids and triglycerides, was analysed. Our data indicate that at 4 and 6 hours after paracetamol giving GSH content of liver tissue appears reduced to about 27 and 38% of the control values, respectively. In the latter phases (8 and 24 hours) the concentration of GSH gradually tends to regain the values as estimated in untreated rats. At the same time the production of TBA-reacting substances is markedly increased. In spite of these biochemical disturbances not signs of both liver necrosis and hepatocellular degeneration was found. In fact, only at 24 hours after hepatotoxin a slight increase (P 0.05) of serum activity of alanine-amino transferase and of triglyceride content in the liver was revealed. The relationship between the hepatic GSH depletion and the increased production of TBA-reacting substances is discussed.

[The content of reduced glutathione in rat liver after poisoning with white phosphorus]. / Contenuto di glutatione ridotto nel fegato di ratto dopo intossicazione con fosforo bianco.

The content of hepatic GSH was evaluated in rats after poisoning with white phosphorus. In addition, liver damage following the administration of the hepatotoxin was assessed by determining hepatic triglyceride accumulation. Experiments in parallel were carried out in an attempt to evaluate the enhanced susceptibility of hepatic tissue to peroxidative decomposition of unsaturated lipids 'in vitro', as measured by the production of TBA-reacting substances. Our data indicate that only in the early stage of intoxication is it possible to detect a slight decrease of GSH content in the liver, while during the subsequent stages the concentration of GSH was unaffected. At 6 hours of intoxication the level of hepatic triglycerides was significantly increased. Pretreatment with GSH was followed by an amelioration of fatty infiltration, but the content of hepatic GSH was unchanged. The production of TBA-reacting products was found enhanced only at 6 hours of intoxication. These results are discussed in relation to the role of lipid peroxidation in liver injury by white phosphorus.