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

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.

Serum myoglobin/carbonic anhydrase III ratio as a marker of reperfusion after myocardial infarction.

BACKGROUND: Coronary patency is important for short- and long-term outcome after myocardial infarction. Serum myoglobin concentration is a sensitive marker of myocardial damage and its specificity can be improved by simultaneous measurement of carbonic anhydrase III, a skeletal muscle marker. In the present study we evaluated the role of myoglobin/carbonic anhydrase III ratio as a non-invasive marker of reperfusion. METHODS: We measured myoglobin, carbonic anhydrase III and creatine kinase MB-fraction release serially in 29 patients with acute myocardial infarction treated with thrombolysis and in 28 patients treated with primary coronary angioplasty. RESULTS: Thrombolytic therapy was followed by a 9.1+/-2.2-fold increase in myoglobin and 10.8+/-3.3-fold increase in creatine kinase MB-fraction during the first hour of treatment, while carbonic anhydrase III remained unchanged. The peak value of myoglobin/carbonic anhydrase III ratio was found at 2 h and that of creatine kinase MB-fraction at 8 h after thrombolysis. Knowledge of the reperfusion time point during primary angioplasty and follow-up of cardiac markers revealed that cut-off points of 3 and 10 h for the peak values of myoglobin/carbonic anhydrase III ratio and creatine kinase MB-fraction can be used as indicators for reperfusion, respectively. Myoglobin/carbonic anhydrase III ratio measured before treatment and at 2 and 4 h after the onset of treatment screened 23 of those 25 patients with probable reperfusion after thrombolysis. CONCLUSIONS: We conclude that measuring myoglobin/carbonic anhydrase III ratio during the first hours after initiation of thrombolysis may be useful in evaluating the success of reperfusion after acute myocardial infarction.