Synergistic toxicity of cyclosporin A and streptomycin in renal epithelial cell cultures.
Cyclosporin A (CSA) nephrotoxicity was examined in two renal epithelial cell cultures, the LLC-PK1 cell line and the MDCK cell line. Acute changes in cell growth and cellular DNA and protein synthesis were investigated at 2 hours, 20 hours and 5 days. The potential synergistic interaction between streptomycin (a standard additive to most culture media) and CSA was examined. CSA produced significant alterations in cell function as early as 2 hours after exposure and this became more noticeable with increased exposure to CSA. Streptomycin potentiated the toxicity effects on cellular metabolism that was seen with CSA. The use of cell culture models to investigate CSA toxicity must avoid the use of potential agents which may have a synergistic effect on the development of toxicity.
Walker
R J
RJ
Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, Australia.
Lazzaro
V A
VA
Duggin
G G
GG
Horvath
J S
JS
Tiller
D J
DJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003524:Cyclosporins / Q000008:administration & dosage / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D004848:Epithelium; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis; D013307:Streptomycin / Q000008:administration & dosage / Q000633:toxicity*
D003524:Cyclosporins; D004247:DNA; D013307:Streptomycin