Hepatocellular cytoprotection against the pathobiologic effects of thiacetarsamide in vitro and in vivo using N-acetyl-L-cysteine

This project investigated N-acetyl-L-cysteine (NAC) for its effect on T-induced cytotoxicity in vitro using NCTC 1465 (murine transformed hepatoma) cell culture. Sigmoid lethality concentration curves (LC) were established for T using varying times of exposure to T, incubation following exposure, and varying concentrations of T. An LC$\sb{50}$ was consistently found between the (1 to 3X) of T with 4 hours exposure and 24 hours incubation. A series of 3 experiments were performed with simultaneous of NAC and T. NAC was in the media during the exposure to T (4 hr) in the first, during the incubation (24 hr) in the second, and during both (28 hr) in the third. Cytoprotection in all three experiments was found as a shift of LC curves to the right using the (1 to 10X) of NAC.

Pretreatment effects of NAC and dextrose (D) upon hepatocellular toxicity of T in vivo, in normal dogs, were also investigated. Thiacetarsamide caused a predominance of periportal (acinar zone 1) hepatocellular necrosis with accompanying inflammation. (Abstract shortened by UMI.).