Brandt 2014 Chem Biol Interact
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 50ΞΌM) on rat hepatocytes to determine its cytotoxicity on non-tumor cells. SYD-1 (25 and 50 ΞΌM) 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 βΌ66% as a consequence of treatment with SYD-1 (50 ΞΌM) for 18 h. Under the same conditions, SYD-1 promoted an increase in the release of LDH by βΌ19%. The morphological changes in the cultured cells treated with SYD-1 (50 ΞΌM) 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 ΞΌM), 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 βΌ36%, whereas the lactate levels were increased by βΌ22% (for the 50 ΞΌM treatment). The basal and uncoupled states of respiration of the cultured hepatocytes were inhibited by βΌ79% and βΌ51%, respectively, by SYD-1 (50 ΞΌM). In these cells, SYD-1 (50 ΞΌM) increased the pyruvate and lactate levels by βΌ84% and βΌ16%, 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. β’ 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