Thiazolidinedione toxicity to isolated hepatocytes revealed by coherent multiprobe flourescence microscopy and correlated with multiparameter flow cytometry of peripheral leukocytes
dc.contributor.author | Rahbari, Ramin | en_US |
dc.contributor.author | de la Iglesia, Felix A. | en_US |
dc.contributor.author | Rowley, Jon A. | en_US |
dc.contributor.author | Haskins, Jeffrey R. | en_US |
dc.date.accessioned | 2006-09-08T19:46:46Z | |
dc.date.available | 2006-09-08T19:46:46Z | |
dc.date.issued | 2001-09 | en_US |
dc.identifier.citation | Haskins, Jeffrey R.; Rowse, Paul; Rahbari, Ramin; de la Iglesia, Felix A.; (2001). "Thiazolidinedione toxicity to isolated hepatocytes revealed by coherent multiprobe flourescence microscopy and correlated with multiparameter flow cytometry of peripheral leukocytes." Archives of Toxicology 75(7): 425-438. <http://hdl.handle.net/2027.42/41920> | en_US |
dc.identifier.issn | 0340-5761 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/41920 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=11693184&dopt=citation | en_US |
dc.description.abstract | Thiazolidinediones (TZDs) are effective for the treatment of adult-onset insulin-resistant diabetes. Unfortunately, TZDs are associated with sporadic hepatic dysfunction that is not predictable from experimental animal studies. We investigated the response of isolated rat and human hepatocytes to various TZDs using biochemical assays, coherent multiprobe fluorescence microscopy and flow cytometric analyses. The results identified direct effects of TZD on mitochondria from live human and rodent hepatocytes. The multiprobe fluorescence assays showed disruption of mitochondrial activity as an initiating event followed by increased membrane permeability, calcium influx and nuclear condensation. Other TZD-related cellular effects were increased hepatic enzyme leakage, decreased reductive metabolism and cytoplasmic adenosine triphosphate depletion. Mitochondrial effects were similar in cryopreserved hepatocytes from diabetic or non-diabetic donors. Peripheral blood mononuclear cells (PBMCs) had baseline mitochondrial energetics and metabolism comparable with isolated hepatocytes. Mitochondrial effects in isolated hepatocytes were found in human PBMCs exposed to the TZDs. The relative potency of TZDs for causing hepatocyte and PBMC effects was troglitazone >pioglitazone >rosiglitazone. These studies clearly demonstrated that hepatic alterations in vitro are characteristic of TZDs, with only quantitative differences in subcellular organelle dysfunction. Monitoring mitochondrial function in isolated PBMCs may be beneficial in diabetics undergoing TZD therapy. | en_US |
dc.format.extent | 512365 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Springer-Verlag | en_US |
dc.subject.other | Legacy | en_US |
dc.subject.other | Thiazolidinediones Peripheral Leukocytes in Vitro Comparative Toxicity Liver | en_US |
dc.title | Thiazolidinedione toxicity to isolated hepatocytes revealed by coherent multiprobe flourescence microscopy and correlated with multiparameter flow cytometry of peripheral leukocytes | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pathology, The University of Michigan Medical School, 7520 A MSRB-I, 1150 W Medical Center Drive, Ann Arbor, Michigan 48109, USA, | en_US |
dc.contributor.affiliationother | Drug Safety Evaluation, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA, | en_US |
dc.contributor.affiliationother | Drug Safety Evaluation, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA, | en_US |
dc.contributor.affiliationother | Drug Safety Evaluation, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA, | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 11693184 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/41920/1/204-75-7-425_s002040100251.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1007/s002040100251 | en_US |
dc.identifier.source | Archives of Toxicology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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