Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Thiazolidinedione toxicity to isolated hepatocytes revealed by coherent multiprobe fluorescence microscopy and correlated with multiparameter flow cytometry of peripheral leukocytes
Autore:
Haskins, JR; Rowse, P; Rahbari, R; de la Iglesia, FA;
Indirizzi:
Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 Dept Pathol, Ann Arbor, MI 48109 USA Pfizer Global Res & Dev, Drug Safety Evaluat, Ann Arbor, MI 48105 USA Pfizer Global Res & Dev Ann Arbor MI USA 48105 t, Ann Arbor, MI 48105 USA
Titolo Testata:
ARCHIVES OF TOXICOLOGY
fascicolo: 7, volume: 75, anno: 2001,
pagine: 425 - 438
SICI:
0340-5761(200109)75:7<425:TTTIHR>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTIDIABETIC AGENT CS-045; DIABETES-MELLITUS; HEPATIC-FAILURE; INSULIN ACTION; CELL-DEATH; IN-VITRO; TROGLITAZONE; MECHANISM; RATS; HEPATOTOXICITY;
Keywords:
thiazolidinediones; peripheral leukocytes; in vitro; comparative toxicity; liver;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: de la Iglesia, FA Univ Michigan, Sch Med, Dept Pathol, 7520 A MSRB-I,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA Univ Michigan 7520 A MSRB-I,1150 W Med Ctr Dr Ann Arbor MI USA 48109
Citazione:
J.R. Haskins et al., "Thiazolidinedione toxicity to isolated hepatocytes revealed by coherent multiprobe fluorescence microscopy and correlated with multiparameter flow cytometry of peripheral leukocytes", ARCH TOXIC, 75(7), 2001, pp. 425-438

Abstract

Thiazolidinediones (TZDs) are effective for the treatment of adult-onset insulin-resistant diabetes. Unfortunately, TZDs are associated with sporadichepatic 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 increasedhepatic 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 isolatedhepatocytes 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 hepaticalterations 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 01:15:20