A Single Zidovudine (AZT) Administration Delays Hepatic Cell Proliferation by Altering Oxidative State in the Regenerating Rat Liver
Por:
Butanda-Ochoa, Armando, Rolando Hernandez-Espinosa, Diego, Olguin-Martinez, Marisela, Sanchez-Sevilla, Lourdes, Rodriguez, Mario R., Chavez-Renteria, Benito, Aranda-Fraustro, Alberto, Hernandez-Munoz, Rolando
Publicada:
1 ene 2017
Resumen:
The 3'-azido-3'-deoxythymidine or Zidovudine (AZT) was the first
antiretroviral drug used in the treatment of HIV patients, which has
good effectiveness but also hepatotoxic side effects that include cell
cycle arrest and oxidative/nitrative mitochondrial damage. Whether such
an oxidative damage may affect the proliferative-regenerative capacity
of liver remains to be clearly specified at doses commonly used in the
clinical practice. In this study, we described the
oxidative-proliferative effect of AZT administered at a common clinical
dose in rat liver submitted to 70% partial hepatectomy (PH). The
results indicate that AZT significantly decreased DNA synthesis and the
number of mitosis in liver subjected to PH in a synchronized way with
the promotion of organelle-selective lipid peroxidation events
(especially those observed in plasma membrane and cytosolic fractions)
and with liver enzyme release to the bloodstream. Then at the dose used
in clinical practice AZT decreased liver regeneration but stimulates
oxidative events involved during the proliferation process in a way that
each membrane system inside the cell preserves its integrity in order to
maintain the cell proliferative process. Here, the induction of large
amounts of free ammonia in the systemic circulation could become a
factor capable of mediating the deleterious effects of AZT on PH-induced
rat liver regeneration.
Filiaciones:
Butanda-Ochoa, Armando:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Mexico City 04510, DF, Mexico
Rolando Hernandez-Espinosa, Diego:
Univ Nacl Autonoma Mexico, Dept Neurodesarrollo & Fisiol, Inst Fisiol Celular, Mexico City 04510, DF, Mexico
Olguin-Martinez, Marisela:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Mexico City 04510, DF, Mexico
Sanchez-Sevilla, Lourdes:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Mexico City 04510, DF, Mexico
Rodriguez, Mario R.:
Univ Nacl Autonoma Mexico, Dept Neurodesarrollo & Fisiol, Inst Fisiol Celular, Mexico City 04510, DF, Mexico
Chavez-Renteria, Benito:
Inst Nacl Cardiol Ignacio Chavez, Dept Patol, Mexico City 14080, DF, Mexico
Aranda-Fraustro, Alberto:
Inst Nacl Cardiol Ignacio Chavez, Dept Patol, Mexico City 14080, DF, Mexico
Hernandez-Munoz, Rolando:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Mexico City 04510, DF, Mexico
|