Kinetics of mRNA expression of alkaline phosphatase isoenzymes in hepatic tissues from glucocorticoid-treated dogs

Wiedmeyer, Charles E.; Solter, Philip F.; Hoffmann, Walter

doi:10.2460/ajvr.2002.63.1089

Cited by 15 publications

(15 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increases in ALP activity can be detected in the liver, kidneys, and intestinal tract as well as in the serum of dogs treated with prednisone, but the greatest increases in tissue activity (of all isoforms, including intestinal ALP) are seen in the liver 39. The steroid ALP isoform is synthesized in the canine liver, but not in the intestine or kidneys 40. Glucocorticoids are thought to influence tissue ALP activity both at the level of gene transcription and post‐transcriptionally, depending on the organ and ALP isoform involved 39…”

Section: Induction By Glucocorticoids and Anticonvulsantsmentioning

confidence: 99%

“…By day 10, bone ALP activity in serum was significantly increased, and comprised a larger proportion of total ALP activity than steroid ALP (approximately 10%). The delay in the increase of steroid ALP activity in serum as compared to liver ALP activity may reflect delayed expression of the steroid ALP gene in liver tissue in response to glucocorticoid treatment, although the mechanism responsible for the delay is not clear 40…”

Section: Induction By Glucocorticoids and Anticonvulsantsmentioning

confidence: 99%

See 1 more Smart Citation

Alkaline phosphatase: beyond the liver

Fernandez

Kidney

2007

Veterinary Clinical Pathol

215

119

View full text Add to dashboard Cite

The alkaline phosphatases comprise a heterogeneous group of enzymes that are widely distributed in mammalian cells. They often are associated with cell membranes, but their exact physiologic function is unknown. Despite this, alkaline phosphatase activity is a very useful serum biochemical indicator of liver disease, particularly cholestatic disease. However, increases in the activity of alkaline phosphatase in serum and other body fluids may reflect physiologic or pathologic changes beyond those of hepatic origin. For example, nonhepatic increases in serum alkaline phosphatase activity are found in young animals, in pregnant and lactating females, and in association with high fat diets. Bone disease, endocrine disease, neoplasia, and other disorders can result in increased alkaline phosphatase activity. In addition, alkaline phosphatase activity may be increased due to induction by certain drugs such as glucocorticoids and anticonvulsants. In this article, we will review the physiologic and pathologic factors influencing the activity of alkaline phosphatase in serum and other body fluids, with an emphasis on disorders beyond liver disease. (Vet Clin Pathol. 2007;36:223-233)

show abstract

Section: Induction By Glucocorticoids and Anticonvulsantsmentioning

confidence: 99%

Section: Induction By Glucocorticoids and Anticonvulsantsmentioning

confidence: 99%

Alkaline phosphatase: beyond the liver

Fernandez

Kidney

2007

Veterinary Clinical Pathol

215

119

View full text Add to dashboard Cite

show abstract

“…In dogs given prednisone, increases in hepatic ALP and GGT, but not ALT, activities are seen, often along with increases in serum ALP, GGT, and ALT activities (Rutgers 1995;Solter et al 1994). Increased serum activity of the liver ALP isoenzyme (LALP) can occur following a single dose of prednisone in the dog (Wiedmeyer et al 2002a); however, significant increases in serum CIALP activity do not occur before seven to ten days of prednisone administration (Solter et al 1994;Wiedmeyer et al 2002b). These differences are related in part to different regulatory mechanisms, as the onset of hepatic CIALP mRNA expression is delayed in comparison to LALP mRNA (Wiedmeyer et al 2002b).…”

Section: Corticosteroid-mediated Induction Of Hepatobiliary Biomarkermentioning

confidence: 99%

“…Increased serum activity of the liver ALP isoenzyme (LALP) can occur following a single dose of prednisone in the dog (Wiedmeyer et al 2002a); however, significant increases in serum CIALP activity do not occur before seven to ten days of prednisone administration (Solter et al 1994;Wiedmeyer et al 2002b). These differences are related in part to different regulatory mechanisms, as the onset of hepatic CIALP mRNA expression is delayed in comparison to LALP mRNA (Wiedmeyer et al 2002b). Corticosteroidmediated induction and release of both ALP and GGT into serum in the dog occurs independently of cholestasis, as both hepatic and serum bile acid concentrations are unchanged in dogs given prednisone (Solter et al 1994).…”

Section: Corticosteroid-mediated Induction Of Hepatobiliary Biomarkermentioning

confidence: 99%

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

et al. 2010

View full text Add to dashboard Cite

Hepatic drug-metabolizing enzyme (DME) induction is an adaptive response associated with changes in preclinical species; this response can include increases in liver weight, hepatocellular hyperplasia and hypertrophy, and upregulated tissue expression of DMEs. Effects of DME induction on clinical pathology markers of hepatobiliary injury and function in animals as well as humans are not well established. This component of a multipart review of the comparative pathology of xenobiotically mediated induction of hepatic metabolizing enzymes reviews pertinent data from retrospective and prospective preclinical and clinical studies. Particular attention is given to studies with confirmation of DME induction and concurrent evaluation of liver and/or serum hepatobiliary marker enzyme activities and histopathology. These results collectively indicate that in the rat, when histologic findings are limited to hepatocellular hypertrophy, DME induction is not expected to be associated with consistent or substantive changes in serum or plasma activity of hepatobiliary marker enzymes such as alanine aminotransferase, alkaline phosphatase, and gamma glutamyltransferase. In the dog and the monkey, published studies also do not demonstrate a consistent relationship across DME-inducing agents and changes in these clinical pathology parameters. However, increased liver alkaline phosphatase or gamma glutamyltransferase activity in dogs treated with phenobarbital or corticosteroids suggests that direct or indirect induction of select hepatobiliary injury markers can occur both in the absence of liver injury and independently of induction of DME activity. Although correlations between tissue and serum levels of these hepatobiliary markers are limited and inconsistent, increases in serum/plasma activities that are substantial or involve changes in other markers generally reflect hepatobiliary insult rather than DME induction. Extrahepatic effects, including disruption of the hypothalamic-pituitary-thyroid axis, can also occur as a direct outcome of hepatic DME induction in humans and animals. Importantly, hepatic DME induction and associated changes in preclinical species are not necessarily predictive of the occurrence, magnitude, or enzyme induction profile in humans.

show abstract

“…This is likely due to a combination of events including induction of increased de novo synthesis of cholephilic enzymes in the case of alkaline phosphatase (ALP, EC3.1.3.1) (Hatoff and Hardison, 1979;Solter et al, 1994;Wiedmeyer et al, 2002aWiedmeyer et al, , 2002b. The basolateral appearance of cholephilic enzymes is also facilitated by the fact that after synthesis, all apical enzymes are believed to first be transported to the basolateral surfaces before arriving at their final site on the bile canaliculi (Bartles et al, 1987;Schell et al, 1992;Maurice et al, 1994).…”

Section: Cellular Redistribution Of Cholephilic Enzyme Activitymentioning

confidence: 99%

Clinical Pathology Approaches to Hepatic Injury

Solter

2005

Toxicol Pathol

Self Cite

View full text Add to dashboard Cite

Testing the blood for evidence of hepatic damage and dysfunction frequently involves measuring several blood constituents simultaneously to screen for disease. While useful, this approach occasionally leads to apparent disparities between the blood test results, and the results of other diagnostic tests such as histology. In part, these perceived discrepancies may stem from a lack of appreciation for tissue, cellular, and molecular factors that affect the appearance of hepatic disease biomarkers in the blood. Further confusing the matter is that in some instances the mechanisms responsible for the appearance of diagnostic compounds in blood are only partially understood. Many of the known factors that affect hepatic biomarkers are similar to those affecting other tissue markers, while others are unique to the liver, such as those involved with cholestasis. Disease conditions can also cause misleading results by affecting tissue concentrations of test compounds, hepatic mass, and the clearance rate of compounds from the blood. Knowledge of the factors affecting the blood concentrations of biomarkers, as well as investigations into the mechanisms behind changes to hepatic biomarker concentrations, may allow for a better interpretation of blood test results and fewer inconsistencies between diagnostic results.

show abstract

Kinetics of mRNA expression of alkaline phosphatase isoenzymes in hepatic tissues from glucocorticoid-treated dogs

Abstract: The liver is the most likely source for CIALP in dogs. Analysis of kinetics of serum and hepatic LALP and CIALP mRNA suggests that after glucocorticoid treatment, both are regulated by modification of mRNA transcript concentrations, possibly through differing mechanisms.

Cited by 15 publications

References 39 publications

Alkaline phosphatase: beyond the liver

Alkaline phosphatase: beyond the liver

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

Clinical Pathology Approaches to Hepatic Injury

Contact Info

Product

Resources

About