Sydnone SYD-1 affects the metabolic functions of isolated rat hepatocytes.

Autor: Brandt AP; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., Pires Ado R; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., Rocha ME; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., Noleto GR; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., Acco A; Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., de Souza CE; Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., Echevarria A; Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil., Canuto AV; Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil., Cadena SM; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. Electronic address: silvia.cadena@ufpr.br.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2014 Jul 25; Vol. 218, pp. 107-14. Date of Electronic Publication: 2014 May 15.
DOI: 10.1016/j.cbi.2014.05.002
Abstrakt: 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 50 μM) on rat hepatocytes to determine its cytotoxicity on non-tumor cells. SYD-1 (25 and 50 μM) 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 ∼66% as a consequence of treatment with SYD-1 (50 μM) for 18 h. Under the same conditions, SYD-1 promoted an increase in the release of LDH by ∼19%. The morphological changes in the cultured cells treated with SYD-1 (50 μM) 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 μM), 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 ∼36%, whereas the lactate levels were increased by ∼22% (for the 50 μM treatment). The basal and uncoupled states of respiration of the cultured hepatocytes were inhibited by ∼79% and ∼51%, respectively, by SYD-1 (50 μM). In these cells, SYD-1 (50 μM) increased the pyruvate and lactate levels by ∼84% and ∼16%, 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.
(Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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