Evaluation of phospholipid and liposomal S-adenosyl methionine for the treatment of liver injury in a murine model.
We have used a murine model of Acetaminophen induced hepatoxicity to determine if S-adenosyl methionine 1,4 butanedisulfonate (SD4) in liposomes can prevent liver injury when administered immediately prior to acetaminophen, as judged by serum aspartate aminotransferase and alanine aminotransferase levels, and histological evidence of liver necrosis. No protection was observed when mice received 1 g/kg unencapsulated SD4. Partial protection was observed with 5 or 0.5 mg/kg SD4 in unextruded distearoylphosphatidylglycerol (DSPG) liposomes. Protection comparable to that seen in mice receiving encapsulated SD4 is achieved when mice received lipid alone in equivalent amounts, suggesting that the contribution of encapsulated SD4 to the efficacy of the liposomes may be minimal. Unextruded distearoylphosphatidylcholine (DSPC) liposomes show only slight effects even at 50 mg/kg SD4. This is likely caused by the size of unextruded DSPC lipsomes, because extruded DSPC liposomes, whose size is smaller, are of comparable efficacy to unextruded DSPG liposomes.
Wagner
Eric J
EJ
School of Pharmacy and Veterinary Medicine, University of Wisconsin Madison, 777 Highland Avenue, Madison, Wisconsin, USA.
Brown
Carolyn S
CS
Mather
Jennifer R
JR
Scholcoff
Cecilia
C
Krugner-Higby
Lisa
L
Heath
Timothy D
TD
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D008081:Liposomes / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010715:Phosphatidylglycerols / Q000737:chemistry; D012436:S-Adenosylmethionine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D008081:Liposomes; D010715:Phosphatidylglycerols; C468227:adenosyl-methionine 1,4-butanedisulfonate; C084352:distearoyl phosphatidylglycerol; D012436:S-Adenosylmethionine