S-ADENOSYLMETHIONINE DEFICIENCY AND TNF-ALPHA IN LIPOPOLYSACCHARIDE-INDUCED HEPATIC-INJURY

S-adenosylmethionine (Adomet) is a substrate for de novo synthesis of choline. Adomet deficiency occurs in certain types of liver injury, an d the injury is attenuated by exogenous Adomet. Tumor necrosis factor- alpha (TNF-alpha) is also a mediator of these models of hepatotoxicity . We investigated the role of Adomet in lipopolysaccharide (LPS)-induc ed liver injury in rats made deficient in both Adomet and choline. Rat s were maintained on either a methionine-restricted and choline-defici ent (MCD) diet or a diet containing sufficient amounts of all nutrient s [methionine and choline sufficient (MCS)] and then administered eith er LPS or saline. MCS-LPS rats had normal liver histology and no chang e in serum transaminases compared with the MCS-saline control group. M CD-saline rats had hepatosteatosis but no necrosis, and a five- to sev enfold increase in transaminases vs. the MCS-saline group. MCD-LPS rat s additionally had hepatonecrosis and a 30- to 50-fold increase in tra nsaminases. Exogenous Adomet administration to MCD-LPS rats corrected the hepatic deficiency of Adomet but not of choline, prevented necrosi s but not steatosis, and attenuated transaminases. Serum TNF-alpha was sixfold higher in MCD rats even without LPS challenge and 300-fold hi gher with LPS challenge. Exogenous Adomet attenuated increased serum T NF-alpha in MCD-LPS rats.