Accession Number:

ADA218355

Title:

Comparative Toxicity of Cyclic Peptides and Depsipeptides in Cultured Rat Hepatocytes

Descriptive Note:

Corporate Author:

ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD

Report Date:

1989-01-01

Pagination or Media Count:

3.0

Abstract:

Low-molecular-weight MW, cyclic peptides peptides linked through an amide linkage and depsipeptides peptides linked through an ester linkage comprise a small group of metabolites produced by fungi, algae or bacteria. Among these cyclic peptides are cyclosporine MW 1203, gramicidin-S MW 1141 and enniatin-B MW 639 represent cyclic depsipeptides. These cyclic compounds possess varied pharmacological properties, ranging from antimicrobial activity valinomycin, enniatin-B, gramicidin-S, microcystin-LR and strong immunosuppressive activity cyclosporine, to antimalarial activity valinomycin, cyclosporine, gramicidin. The toxicity LD50 of these compounds is in the range of microgram microcystin-LR, 56 microgramskg, i.p., mice to milligram cyclosporine, 107 microgramskg, i.v., mice 2 quantities. Although mice treated with 200 microgramskg day of cyclosporine, or sublethal doses of microcystin-LR, developed hepatic vascular congestion and fatty liver, there is no information available on the hepatotoxicity of the other cyclic peptides and depsipeptides. Microcystin-LR induces liver damage in mice and necrosis of cultured hepatocytes after several hours of incubation with the toxin. This study was designed to compare cell injury induced by these cyclic peptides and depsipeptides using the release of LDH and Carbon 14 adenine nucleotides from cultured hepatocytes. Reprints.

Subject Categories:

  • Biochemistry
  • Toxicology
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE