The mouse liver slice system as an in vitro model for testing the protective effect of n-acetylcysteine against hepatotoxic agents

Summary: An in vitro liver slice system was used to test the antidotal effect of N-acetylcysteine (NAC) against hepatotoxic agents. Incubation of mouse slices with acetaminophen (APAP) in a concentration of 6.8 mg/ml resulted in lactate dehydrogenase (LDH) leakage from the cells. NAC protected the tissue from APAP-induced hepatocellular damage in a dose-dependent manner. Maximal protection was achieved by 10 mM of the sulfhydryl compound when applied 20 min following APAP intoxication. Longer intervals, concurrent administration, or preincubation of the slices with the SH reagent were less protective against the hepatotoxin. The liver slice system has been used to test NAC antidotal activity against other hepatotoxins known to be metabolized to reactive radicals, such as carbon tetrachloride (CC1₄), bromobenzene, and furosemide. The hepatocellular damage caused by these agents was slightly reduced by the sulfhydryl agent. These findings may demonstrate the ability of the in vitro liver slice system to serve as a tool for primary assessment of the activity of various antidotes against toxic agents.