title: Modulation of balance between apoptosis and proliferation by lipid peroxidation (LPO) during rat liver regeneration.
abstract: BACKGROUND
  This work aims to investigate the role of lipid peroxidation (LPO) at early stages of liver regeneration and to evaluate the balance between apoptosis and cell proliferation during this process.
  
  
  METHODS
  Sham and partial hepatectomized (PH) male Wistar rats were randomized in seven groups: Control (untreated), E-Control (injected with vitamin E-vehicle), C-Control (injected with vitamin C-vehicle), E1 (vitamin E 100 mg/kg body weight), E2 (vitamin E 600 mg/kg body weight), C1 (vitamin C 30 mg/kg body weight), C2 (vitamin C 100 mg/kg body weight).
  
  
  RESULTS
  Vitamin treatments attenuated the increase of LPO level observed in total homogenate and microsomes at 3 and 5 hr after PH. Both antioxidant vitamins attenuated the increase in Bax pro-apoptotic protein and augmented Bcl-xL antiapoptotic protein levels (35%) at 3 and 5 hr post-PH; Bcl-xL/Bax ratio was, therefore, increased. A direct linear relationship between LPO levels and Bax mitochondrial protein levels was seen. Vitamin-treatments diminished the apoptosis index with respect to PH-Control values, so that this parameter showed a linear relationship with LPO levels. At 24 hr after PH, the vitamin treatments increased the peak of [(3) H]-thymidine incorporation into DNA and the proliferative index (PI), measured as PCNA expression; an inverse relationship between PI and LPO levels could be demonstrated.
  
  
  CONCLUSIONS
  Our data show that the diminution of LPO levels by vitamin-treatment post-PH produces both an attenuation of cellular apoptosis and a marked increase in the proliferation process, suggesting that the modulation of LPO has a role in liver regeneration process.
authors.affiliation: Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas (Universidad Nacional de Rosario), Argentina.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Ronco
authors.forename: Maria Luján
authors.initials: ML
authors.lastname: deAlvarez
authors.forename: Juan
authors.initials: J
authors.lastname: Monti
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Carrillo
authors.forename: Gerardo
authors.initials: G
authors.lastname: Pisani
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Lugano
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Carnovale
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D024502:alpha-Tocopherol / Q000494:pharmacology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D024502:alpha-Tocopherol; D001205:Ascorbic Acid