Effect of succinylacetone administration on plasma nitrate levels of lipopolysaccharide-treated mice

Groups of 6 male BALB/c mice were treated twice daily for 4 days with 1000 mg/kg succinylacetone (SA), a heme biosynthesis inhibitor. Liver cytochrome P450 levels were slightly decreased and coumarin hydroxylase activity was increased from 124 ± 35 to 276 ± 37 pmol/mg/min. Renal cytochrome P450 content was decreased by SA treatment. SA had no effect on brain nitric oxide synthase activity. Administration of lipopolysaccharide (LPS) increased plasma nitrite/nitrate levels, and pretreatment with SA for 72 h partially attenuated this effect. Plasma nitrate levels were 305 ± 67 μmol/l in LPS-injected mice and 116 ± 27 μmol/l in LPS-injected, succinylacetone pretreated mice. These results indicate that succinylacetone treatment interferes with the inducible nitric oxide synthase activity or with its activation pathway.