Alternation between dietary protein depletion and normal feeding cause liver damage in mouse

• Published in: Journal of physiology and biochemistry 2011-03, Vol.67 (1), p.43-52
• Main Authors: Caballero, Veronica J., Mendieta, Julieta R., Giudici, Ana M., Crupkin, Andrea C., Barbeito, Claudio G., Ronchi, Virginia P., Chisari, Andrea N., Conde, Ruben D.
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Alanine Transaminase - drug effects; Alanine Transaminase - metabolism; Animal Physiology; Animals; Aspartate Aminotransferases - blood; Aspartate Aminotransferases - drug effects; Aspartate Aminotransferases - metabolism; Biomedical and Life Sciences; Biomedicine; Carbonic Anhydrase III - drug effects; Carbonic Anhydrase III - metabolism; Catalase - drug effects; Catalase - metabolism; Dietary Proteins - administration & dosage; Fatty Acid Synthases - drug effects; Fatty Acid Synthases - metabolism; Female; Glutathione Peroxidase - drug effects; Glutathione Peroxidase - metabolism; Glutathione Reductase - drug effects; Glutathione Reductase - metabolism; Glutathione Transferase - drug effects; Glutathione Transferase - metabolism; Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) - drug effects; Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) - metabolism; Human Physiology; Lipid Peroxidation; Liver - drug effects; Liver - metabolism; Liver - pathology; Malnutrition - metabolism; Mice; Mice, Inbred BALB C; Original Article; Oxidative Stress - drug effects; Protein Carbonylation - drug effects
• ISSN: 1138-7548; 1877-8755
• DOI: 10.1007/s13105-010-0047-1

The effect of frequent protein malnutrition on liver function has not been intensively examined. Thus, the effects of alternating 5 days of a protein and amino acid-free diet followed by 5 days of a complete diet repeated three times (3 PFD-CD) on female mouse liver were examined. The expression of carbonic anhydrase III (CAIII), fatty acid synthase (FAS), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and glutathione S -transferase P1 (GSTP1) in liver were assessed by proteomics, reverse transcriptase-polymerase chain reaction and Northern blotting. The activities of liver GSTs, glutathione reductase (GR) and catalase (CAT), as well as serum glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) were also tested. Additionally, oxidative damage was examined by measuring of protein carbonylation and lipid peroxidation. Liver histology was examined by light and electron microscopy. Compared with control mice, 3 PFD-CD increased the content of FAS protein (+90%) and FAS mRNA (+30%), while the levels of CAIII and CAIII mRNAs were decreased (−48% and −64%, respectively). In addition, 3 PFD-CD did not significantly change the content of GSTP1 but produced an increase in its mRNA level (+20%), while it decreased the activities of both CAT (−66%) and GSTs (−26%). After 3 PFD-CD, liver protein carbonylation and lipid peroxidation were increased by +55% and +95%, respectively. In serum, 3 PFD-CD increased the activities of both SGOT (+30%) and SGPT (+61%). In addition, 3 PFD-CD showed a histological pattern characteristic of hepatic damage. All together, these data suggest that frequent dietary amino acid deprivation causes hepatic metabolic and ultrastructural changes in a fashion similar to precancerous or cancerous conditions.