The protection from hepatotoxicity of some compounds by the synthetic immunomodulator muramyl dipeptide (MDP) in rat hepatocytes and in vivo.
Muramyl dipeptide (MDP) protection from acrolein, chloroform and carbon tetrachloride toxicity was tested using isolated rat hepatocytes prepared by collagenase perfusion method. Hepatotoxin lethal effects were assessed using trypan blue exclusion and ascertained by LD leakage test. Incubation of hepatocyte suspensions with acrolein (143 mumol/ml), CHCl3 (124 mumol/ml) and CCl4 (103.5 mumol/ml) for 15 min reduced viability to 62%, 13% and 27%, respectively. Pretreatment of hepatocytes in incubation media with MDP (20.6 nmol/ml) increased viability significantly to 83%, 27% and 46%, respectively (P less than 0.01 and P less than 0.05). MDP single treatment in vivo (8.26 mumol/kg) produced a three-fold decrease in the high serum aspartate and alanine transaminases induced by CCl4 (5.2 mmol/kg). MDP modulation of CCl4 hepatotoxicity was not accompanied by reduction of lipid peroxides either in liver homogenates, microsomes or hepatocytes in the present conditions. It is suggested that MDP in certain dosages may produce nonspecific stabilization of cytoplasmic membranes towards the studied cytotoxins.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000171:Acrolein / Q000633:toxicity; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D000637:Transaminases / Q000097:blood
D008054:Lipid Peroxides; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000171:Acrolein; D002251:Carbon Tetrachloride; D000637:Transaminases; D002118:Calcium