Inhibition of carbon tetrachloride-induced hepatotoxicity by neopterins

We investigated the inhibitory effects of neopterin (NP) and its reduced form, 5,6,7,8-tetrahydroneopterin (NPH4), on carbon tetrachloride (CCl4)-induced hepatotoxicity. In in vivo experiments, intraperitoneal administration of NP or NPH4 significantly inhibited the elevation of plasma alanine aminotransferase activity induced by CCl4 in mice. In in vitro experiments using cultured rat hepatocytes, CCl4 induced in a manner which was both time- and dose-dependent lactate dehydrogenase release, and the addition of NP or NPH4 to the culture-medium significantly inhibited its release from cells. NPH4, but not NP, reacted directly with a stable radical, 1,1-diphenyl-2-picrylhydrazyl. These results suggest that NP and NPH4 inhibit CCl4-induced hepatotoxicity through different mechanisms.