Rat liver injury induced by hypoxic ischemia and reperfusion: protective action by somatostatin and two derivatives.
Natural somatostatin and two synthetic derivatives (octreotide, 008) were tested for their ability to prevent hypoxic ischemic cell injury of the isolated perfused rat liver. The cyclic octapeptide octreotide is known to have endocrine and cytoprotective activities, whereas the cyclic hexapeptide 008 exerts protective actions without any endocrine effects. In isolated perfused rat livers flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. LDH and GLDH activity as well as Ca2+ concentration was determined in the effluent. Hypoxic ischemia led to a substantial enzyme release from the liver and to a strong Ca2+ influx. Pretreatment with somatostatin, octreotide and 008 significantly reduced LDH and GLDH release (P < 0.001). The somatostatins significantly increased the Ca(2+)-influx into the hypoxic, ischemic perfused rat liver (P < 0.001). Ca(2+)-influx is known to be an essential factor in the final common pathway of cell death induced by hypoxic ischemia. Even though the administration of the somatostatins was associated with an enhanced Ca(2+)-influx, the somatostatins reduced hypoxic ischemic liver injury.
Kusterer
K
K
Center of Internal Medicine, University of Frankfurt, Frankfurt am Main, Germany.
Blöchle
C
C
Konrad
T
T
Palitzsch
K D
KD
Usadel
K H
KH
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects*; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D066298:In Vitro Techniques; D007511:Ischemia / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D008969:Molecular Sequence Data; D015282:Octreotide / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D010456:Peptides, Cyclic; C067675:cyclosomatostatin; D013004:Somatostatin; D007770:L-Lactate Dehydrogenase; D005969:Glutamate Dehydrogenase; D015282:Octreotide; D002118:Calcium