Muramyl dipeptide and carbon tetrachloride hepatotoxicity in rats: involvement of plasma membrane and calcium homeostasis in protective effect.
The present study was carried out to investigate the effect of single and multiple doses of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) on CCl4-induced hepatotoxicity, and hence some of the mechanisms involved. MDP (8.26 mumol/kg i.v.) was administered to rats according to different protocols followed by a single dose of CCl4 (5.2 mmol/kg i.p.), and either the hepatocytes were subsequently isolated and tested for viability and lipid peroxides formation or the level of serum aminotransferases and lactate dehydrogenase (LD) was measured. The results clearly indicate that MDP pretreatment in a single dose reduced CCl4 hepatotoxicity as judged from viability tests as well as reduction of elevated lipid peroxides induced by CCl4 administration. The level of lactate dehydrogenase was also brought to normal value by single MDP administration. MDP also decreased significantly the CCl4-elevated Ca2+ content of isolated hepatocytes and postmicrosomal supernatant Ca2+. 14C-palmitic acid incorporation was increased significantly for neutral lipids and/or phospholipids in hepatocytes and certain subcellular fractions under MDP treatment in vivo. A different effect was seen after multiple MDP administration which further increased CCl4-induced elevation of aminotransferases. Even the repeated administration of MDP without CCl4 increased the level of the latter enzymes. It may be concluded that a single administration of MDP can protect liver cells from CCl4 injury by a mechanism affecting the plasma membrane.