scholarly journals The effect of pyridoxal-5-phosphate on serum alanine aminotransferase activity in dogs suffering from canine babesiosis

2009 ◽  
Vol 76 (3) ◽  
Author(s):  
E.C. Myburgh ◽  
A. Goddard

Accurate measurements of serum aminotransferase (ALT) activity in dogs relies on the endogenous pro-enzyme pyridoxal 5-phosphate (P5P). The purpose of this study was to determine whether the exclusion of P5P from the analytical method causes an underestimation of serum ALT activity in dogs suffering from babesiosis and in those manifesting evidence of hepatocellular damage, and to determine if anorexia causes sufficient P5P depletion to affect in vitro serum ALT activity. One-hundred-and-twenty healthy control dogs and 105 Babesia-infected dogs were included in the study. Two methods for ALT measurement were used: Method 1 included P5P, and Method 2 excluded P5P from the reaction mixture. Higher serum ALT activity was measured with Method 1 in the Babesia-infected dogs (P < 0.001), as well as in 14 dogs with suspected hepatocellular damage (P = 0.03). Duration of anorexia had no effect, irrespective of the method used. Although inclusion of P5P to the reaction mixture consistently resulted in higher measured serum ALT activity, the differences were too small to have led to incorrect diagnoses in the Babesia-infected dogs suspected of liver disease.

2001 ◽  
Vol 281 (6) ◽  
pp. G1423-G1431 ◽  
Author(s):  
Frederic Moulin ◽  
Bryan L. Copple ◽  
Patricia E. Ganey ◽  
Robert A. Roth

Bacterial endotoxin [lipopolysaccharide (LPS)] causes liver injury in vivo that is dependent on platelets, neutrophils [polymorphonuclear leukocytes (PMNs)], and several inflammatory mediators, including thrombin. We tested the hypothesis that thrombin contributes to LPS-induced hepatocellular injury through direct interactions with platelets and/or PMNs in vitro. Perfusion of isolated livers from LPS-treated rats with buffer containing thrombin resulted in a significant increase in alanine aminotransferase (ALT) activity in the perfusion medium, indicating hepatocellular damage. This effect was completely abolished by prior depletion of PMNs from the LPS-treated donor rats but not by depletion of platelets, suggesting interaction between thrombin and PMNs in the pathogenesis. Thrombin did not, however, enhance degranulation of rat PMNs in vitro, and it was not directly toxic to isolated rat hepatocytes in the presence of PMNs even after LPS exposure, suggesting that hepatocellular killing by the PMN-thrombin combination requires the intervention of an additional factor(s) within the liver. In livers from naive donors perfused with buffer containing PMNs and LPS, no injury occurred in the absence of thrombin. Addition of thrombin (10 nM) to the medium caused pronounced ALT release. These results indicate that thrombin and PMNs are sufficient extrahepatic requirements for LPS-induced hepatocellular damage in intact liver.


2013 ◽  
Vol 5 ◽  
pp. CMT.S11120
Author(s):  
Edwin K. Kuffner ◽  
Kimberly M. Cooper ◽  
Jeffrey S. Baggish ◽  
Joseph M. Lynch ◽  
Brenda A. Zimmerman ◽  
...  

Published analyses have noted elevated alanine aminotransferase (ALT) activity in patients taking up to 4000 mg/day of acetaminophen. Data from 3 osteoarthritis trials of acetaminophen 3900–4000 mg/day in which ALT and aspartate aminotransferase (AST) were recorded within approximately 2 weeks of therapy initiation were retrospectively analyzed. Patients with baseline ALT or AST above the upper limit of the reference range (ULRR) were excluded. Among 466 patients, 376 (80.7%) had no ALT elevations within approximately 2 weeks of treatment initiation. Elevations >1.5 and >3.0 times ULRR occurred in 4.5% and 0.9% of patients, respectively. Elevations were transient as most resolved (72.9%) or declined (22.4%) with continued treatment beyond 2 weeks. Within approximately 2 weeks of therapy initiation, no patient had ALT > 5 times ULRR or ALT > 3 times ULRR combined with bilirubin >2 times ULRR. ALT elevations were transient and asymptomatic; almost all resolved or declined while on continued therapy and appear not to be clinically important. Clinical trials.gov ID numbers: NCT00240799, NCT00240786


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