Extended rat liver slice survival and stability monitored using clinical biomarkers.
Precision-cut liver slices are reportedly limited as toxicity models by their short half-life in culture. We used traditional clinical chemistry biomarkers and histology to assess a newer procedure for improved liver slice maintenance. Slices from Sprague-Dawley rat livers were well maintained in a roller culture system for up to 10 days based on protein content (60-70% or higher of initial values) and biomarker retention and verified by histological examination of the tissues showing morphological integrity and viability of hepatocyte and biliary regions. Exposure of the slices to geldanamycin (GEL) resulted in loss of slice LDH and transaminase content, with associated depression in ALP and GGT levels and elevated bilirubin, indicating that GEL affects both cell types as occurs in vivo with this hepatobiliary toxicant. Thus, we conclude that liver slices merit further investigation as a general model for chronic as well as acute toxicity studies.
Behrsing
Holger P
HP
SRI International, 333 Ravenswood Ave., Menlo Park, CA 94025, USA.
Vickers
Alison E M
AE
Tyson
Charles A
CA
D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D016227:Benzoquinones; D015415:Biomarkers / Q000032:analysis*; D002470:Cell Survival / Q000502:physiology; D046508:Culture Techniques / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D047029:Lactams, Macrocyclic; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D011809:Quinones / Q000633:toxicity; D051381:Rats; D014021:Tissue Preservation / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*
D016227:Benzoquinones; D015415:Biomarkers; D047029:Lactams, Macrocyclic; D011809:Quinones; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; C001277:geldanamycin