Brandt 2014 Chem Biol Interact: Difference between revisions
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Revision as of 10:33, 8 November 2016
Brandt AP, do Rocio Andrade Pires A, Rocha ME, Noleto GR, Acco A, de Souza CE, Echevarria A, Dos Santos Canuto AV, Cadena SM (2014) Sydnone SYD-1 affects the metabolic functions of isolated rat hepatocytes. Chem Biol Interact 218C:107-14. |
Brandt AP, do Rocio Andrade Pires A, Rocha ME, Noleto GR, Acco A, de Souza CE, Echevarria A, Dos Santos Canuto AV, Cadena SM (2014) Chem Biol Interact
Abstract: Previously, we demonstrated that sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) impairs the mitochondrial functions linked to energy provision and suggested that this effect could be associated with its antitumor activity. Herein, we evaluated the effects of SYD-1 (25 and 50ฮผM) on rat hepatocytes to determine its cytotoxicity on non-tumor cells. SYD-1 (25 and 50 ฮผM) did not affect the viability of hepatocytes in suspension after 1-40 min of incubation. However, the viability of the cultured hepatocytes was decreased by โผ66% as a consequence of treatment with SYD-1 (50 ฮผM) for 18 h. Under the same conditions, SYD-1 promoted an increase in the release of LDH by โผ19%. The morphological changes in the cultured cells treated with SYD-1 (50 ฮผM) were suggestive of cell distress, which was demonstrated by the presence of rounded hepatocytes, cell fragments and monolayer impairment. Furthermore, fluorescence microscopy showed an increase in the annexin label after treatment with SYD-1 (50 ฮผM), suggesting that apoptosis had been induced in these cells. SYD-1 did not affect the states of respiration in the suspended hepatocytes, but the pyruvate levels were decreased by โผ36%, whereas the lactate levels were increased by โผ22% (for the 50 ฮผM treatment). The basal and uncoupled states of respiration of the cultured hepatocytes were inhibited by โผ79% and โผ51%, respectively, by SYD-1 (50 ฮผM). In these cells, SYD-1 (50 ฮผM) increased the pyruvate and lactate levels by โผ84% and โผ16%, respectively. These results show that SYD-1 affects important metabolic functions related to energy provision in hepatocytes and that this effect was more pronounced on cells in culture than those in suspension. โข Keywords: Sydnones, SYD-1, Hepatocytes, Respiration, Metabolism
Labels: MiParea: Respiration
Stress:Cell death Organism: Rat Tissue;cell: Liver Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
Pathway: ROX
HRR: Oxygraph-2k