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

ABSTRACT

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.