Comparative Toxicity of Cyclic Polypeptides and Depsipeptides on Cultured Rat Hepatocytes
Abstract
Primary cultures of adult rat hepatocytes were used to investigate the comparative toxicity of three cyclic polypeptides (cyclosporine, gramicidin- s, microcystin-LR) and two depsipeptides (enniatin-b and valinomycin). Cell injury was assessed by the release of cellular (14C) adenine nucleotides and lactate dehydrogenase into the media. At Micromole, the cyclic polypeptides (cyclosporine and gramicidin-s) and depsipeptides (enniatin-b and valinomycin) did not induce a significant release of adenine nucleotides or lactate dehydrogenase from cultured rat hepatocytes as compared to controls. However, gramicidin-s, valinomycin, and cyclosporine induced significant cytotoxicity at 50 micromole. Microcystin-LR dose-response studies indicated that maximum cytotoxicity was found at 1 Micromole. Comparatively, gramicidin-s, valinomycin and cyclosporine were at least 50 times less cytotoxic to rat hepatocytes than microcystin-LR. The release of (14C) nucleotides from hepatocytes treated with microcystin-LR was distinctively different by the presence of a lag phase from that observed in hepatocytes treated with the other peptides. Cyclosporine, Valinomycin, Gramicidin-s, Enniatin-b, Microcystin-LR, Cyclic peptides, Cyclic depsipeptide, Hepatocytes, Cytotoxicity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 10, 1989
- Accession Number
- ADA205520
Entities
People
- K. A. Mereish
- R. Bhatnager
- R. Solow
- Y. Singh
Organizations
- United States Army Medical Research Institute of Infectious Diseases