Comparative Toxicity of Cyclic Peptides and Depsipeptides in Cultured Rat Hepatocytes.

摘要

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 micrograms/kg, i.p., mice) to milligram (cyclosporine, 107 micrograms/kg, i.v., mice) 2 quantities. Although mice treated with 200 micrograms/kg /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. (aw)