Sydnone SYD-1 affects the metabolic functions of isolated rat hepatocytes.
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.
Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Anna Paula
AP
Brandt
Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Amanda do Rocio Andrade
Ado R
Pires
Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Maria Eliane Merlin
ME
Rocha
Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Guilhermina Rodrigues
GR
Noleto
Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Alexandra
A
Acco
Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Carlos Eduardo Alves
CE
de Souza
Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil.
Aurea
A
Echevarria
Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil.
André Vinícius dos Santos
AV
Canuto
Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. Electronic address: silvia.cadena@ufpr.br.
Sílvia Maria Suter Correia
SM
Cadena
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
C524256:3-(4-chloro-3-nitrolphenyl)-1,2,3-oxadiazolium-5-olate; D000970:Antineoplastic Agents; D010069:Oxadiazoles; D019344:Lactic Acid; D019289:Pyruvic Acid
Hepatocytes; Metabolism; Respiration; SYD-1; Sydnones