Liver Tyrosine Aminotransferase Research Articles

Validation of Traditional Methods of Genotoxicity with Liver Tyrosine Aminotransferase Activity Induced by Metribuzin Treatment in Albino Rats

The genotoxicity of pesticides give a potential role in population health and ecosystem safety and here the we would like to explore genotoxicity of metribuzin herbicide. Metribuzin dosed orally in albino rats twice per week for 3 months at dose level 0, 110, 220, and 440 mg/kg. All rats were sacrificed and liver was preserved in liquid nitrogen and bone marrow cells was obtained from femur bone. It was founded that chromosomal aberrations were dose dependent with significant increase in all doses (1/20, 1/10 and ⅕ of the LD50% of metribuzin herbicide) specially higher doses represented by structural abnormalities as chromosomal break, fragments, gap, association and a centromeric chromosomes beside numerical abnormalities as polyploidy and hypoploidy. Additionally, DNA quantity was dose dependent significant increase. Notably, there was significant increase in micronuclei level in respect to control that considered as a clastogenic signal and defect in mitotic activity that founded to be decreased in bone marrow cell where the mitotic index had decreased drastically in comparison to control value. Notably, metribuzin enhanced expression of TAT gene at all doses when compared with control group. on conclusion, metribuzin herbicide had a genotoxic properties that constitute hazard and great concern to population and TAT gene expression could be a potential role in detection of toxicity.

In Pursuit of Genes of Glucose Metabolism

If you don't know where you're going, you might wind up someplace else—Yogi Berra My professional journey, once I accepted the fact that I would not play first base for the Chicago Cubs, was not accomplished in a straight line. I entered medical school intending to become a family physician but soon became interested in research. I took an internal medicine residency at the University of California, San Francisco (UCSF), then a long research fellowship in the nascent field of molecular biology at the National Institutes of Health (NIH), and followed that with training in clinical endocrinology at the University of Wisconsin. I spent the next fifteen years dividing my time between the clinic and laboratory at the University of Iowa. Finally, I decided to concentrate on research and spent the next twenty-three years at Vanderbilt University. For the past eleven years, I have been at the University of Iowa, where I helped establish a new diabetes research center. My research journey also had several different directions. Upon reflection, I guess I ended up “someplace else” by choice, and it certainly has been an interesting trip. It is one I unreservedly recommend.

In utero glucocorticoid exposure reduces fetal skeletal muscle mass in rats independent of effects on maternal nutrition

Maternal stress and undernutrition can occur together and expose the fetus to high glucocorticoid (GLC) levels during this vulnerable period. To determine the consequences of GLC exposure on fetal skeletal muscle independently of maternal food intake, groups of timed-pregnant Sprague-Dawley rats (n = 7/group) were studied: ad libitum food intake (control, CON); ad libitum food intake with 1 mg dexamethasone/l drinking water from embryonic day (ED)13 to ED21 (DEX); pair-fed (PF) to DEX from ED13 to ED21. On ED22, dams were injected with [(3)H]phenylalanine for measurements of fetal leg muscle and diaphragm fractional protein synthesis rates (FSR). Fetal muscles were analyzed for protein and RNA contents, [(3)H]phenylalanine incorporation, and MuRF1 and atrogin-1 (MAFbx) mRNA expression. Fetal liver tyrosine aminotransferase (TAT) expression was quantified to assess fetal exposure to GLCs. DEX treatment reduced maternal food intake by 13% (P < 0.001) and significantly reduced placental mass relative to CON and PF dams. Liver TAT expression was elevated only in DEX fetuses (P < 0.01). DEX muscle protein masses were 56% and 70% than those of CON (P < 0.01) and PF (P < 0.05) fetuses, respectively; PF muscles were 80% of CON (P < 0.01). Muscle FSR decreased by 35% in DEX fetuses (P < 0.001) but were not different between PF and CON. Only atrogin-1 expression was increased in DEX fetus muscles. We conclude that high maternal GLC levels and inadequate maternal food intake impair fetal skeletal muscle growth, most likely through different mechanisms. When combined, the effects of decreased maternal intake and maternal GLC intake on fetal muscle growth are additive.

Hepatic tyrosine aminotransferase and glucocorticoid abuse in meat cattle

Besides being extensively applied as therapeutical remedies, glucocorticoids (GCs) - most notably dexamethasone or prednisolone - are also illegally used in livestock for growth-promoting purposes. This study was designed to assess the suitability of liver tyrosine aminotransferase (TAT), a gluconeogenic enzyme known to be induced by GCs, to act as a reliable candidate biomarker to screen for GC abuse in cattle. Enzyme activity was measured spectrophotometrically in liver cytosols or in cell extracts, and TAT gene expression was determined by real-time PCR. Compared with untreated veal calves, a notable scatter (20-fold) and much higher median values (3-fold) characterized TAT specific activity in liver samples from commercially farmed veal calves. A time-related increase in both enzyme activity and gene expression was detected in rat hepatoma cell lines treated with dexamethasone concentrations (10(-8) or 10(-9) m) in the range of those recorded in noncompliant samples from EU official controls. In experimental studies in which finishing bulls were administered GCs at growth-promoting dosages, however, no such changes were recorded in dexamethasone-treated animals; a statistically significant rise in liver TAT activity (+95%) only occurred in prednisolone-treated bulls. Although further research is needed to characterize the GC-mediated response in cattle liver, TAT does not appear to be a specific and sensitive biomarker of GC abuse in the bovine species.

Insights into the mechanisms mediating hyperglycemic and stressogenic outcomes in rats treated with monocrotophos, an organophosphorus insecticide

The present investigation provides mechanistic insights into the hyperglycemic and stressogenic effects of monocrotophos, an organophosphorus insecticide. Pre-treatment of rats with mifepristone (glucocorticoid receptor antagonist) prevented induction of liver tyrosine aminotransferase activity (TAT), but was ineffective in attenuating hyperglycemia induced by monocrotophos. Pre-treatment with propranolol (β-adrenergic receptor antagonist) and phentolamine (α-adrenergic receptor antagonist) were effective in abrogating monocrotophos-induced hyperglycemia. Interestingly, while propranolol offered partial protection against hyperglycemia, phentolamine completely abolished the same. However, monocrotophos-induced hyperlactacidemia was completely abolished by propranolol. Both the adrenoreceptor antagonists, however, failed to attenuate the stressogenic potential of monocrotophos. Hyperglycemia and hyperlactacidemia induced by monocrotophos were abolished by pre-treatment with atropine. Exogenous epinephrine was associated with hyperglycemia and hyperlactacidemia. The impact of adrenergic antagonists on epinephrine-induced hyperglycemia and hyperlactacidemia were remarkably similar to that of monocrotophos-induced hyperglycemia and hyperlactacidemia. Further, hydrazine sulfate (a gluconeogenesis inhibitor) abolished hyperglycemia in monocrotophos-treated rats. From our data, it can be hypothesized that excessive stimulation of adrenoreceptors, probably elicited by increased plasma epinephrine, mediates hyperglycemic outcomes induced by monocrotophos. Pattern of changes in plasma lactate suggests that β-adrenergic activation mediates monocrotophos-induced hyperlactacidemia, while α-adrenergic receptor mediates lactate utilization, leading to hyperglycemia. Induction of liver TAT activity is attributable to glucocorticoid receptor activation as a result of hypercorticosteronemia.

Hyperglycemic and stressogenic effects of monocrotophos in rats : Evidence for the involvement of acetylcholinesterase inhibition

The purpose of this study was to investigate the involvement of acetylcholinesterase (AChE) inhibition in hyperglycemic and stressogenic effects of monocrotophos in rats. Oral administration of monocrotophos (1.8 mg/kg b.w., 1/10 LD 50) caused reversible hyperglycemia in rats with peak increase occurring at 2 h following administration. The hyperglycemic outcome at 2 h was accompanied by significant inhibition of acetylcholinesterase (AChE) activity in brain (84%), adrenal (68%) and liver (53%) and stressogenic effects as revealed by marked increase in plasma corticosterone (102%) and liver tyrosine aminotransferase (TAT) (104%) activity. At 4 h following administration, there was normalization of hyperglycemia and hypercorticosteronemia, marginal attenuation of liver TAT activity and marked increase in liver glycogen content, without spontaneous reactivation of AChE activity in the organs studied. Interestingly, pre-treatment of rats with acetylcholine (ACh) receptor antagonists—atropine sulfate and methyl atropine nitrate offered significant protection against hyperglycemia, hypercorticosteronemia and increased liver TAT activity induced by monocrotophos. Our results clearly demonstrate the involvement of AChE inhibition in hyperglycemia and stressogenic effects of monocrotophos in rats following acute exposure. Protection offered by both, general and peripheral ACh antagonists provide further evidence for the involvement of peripheral AChE inhibition in the monocrotophos-induced effects.

Dietary protein differentially regulates the kinetic behaviour of serine dehydratase and tyrosine aminotransferase of liver and white muscle of rainbow trout (Oncorhynchus mykiss)

We have determined the kinetic behaviour of serine dehydratase (SerDH) and tyrosine aminotransferase (TyrAT) in the liver and white muscle of juvenile rainbow trout (Oncorhynchus mykiss) fed on a low-protein/high-fat (LP/HF) and control diets. The relationship between the kinetic parameters and tissue-DNA concentration has also been determined. SerDH and TyrAT showed hyperbolic kinetics in all cases. The partial replacement of protein with fat significantly increased hepatic SerDH-specific activity, maximum velocity (V(max)) and Michaelis constant (K(m)) while no significant changes were detected in the values of these parameters in white muscle. Nevertheless, hepatic and white-muscle TyrAT specific activity and V(max) decreased in trout fed on LP/HF diet with respect to control. The K(m) of hepatic TyrAT was also lower in trout fed on LP/HF diet than in control. The TyrAT kinetic parameters expressed per cell unit also changed in the same sense as previously described. These results show that, in trout, SerDH and TyrAT are two enzymes regulated by the partial replacement of dietary protein by fat.

Dual Effect of Exogenous Progesterone on the Activity of Tyrosine Aminotransferase in the Liver of Female Rats

An as yet undescribed biphasic response of liver tyrosine aminotransferase (TAT) activity to a single administration of a microcrystallic watery suspension of 25 mg of progesterone (Agolutin Depot, SPOFA Praha) is described in adult female rats subjected to immobilization stress for 150 min. Exaggeration of the stress induced increase of TAT activity 3 and 8 h after hormone administration and its suppression 20 h after it was observed. The stress induced serum corticosterone increase is not correlated with the described changes, however, in non-stressed animals an increased TAT activity at 3 and 8 h after progesterone injection tightly follows the increased plasma corticosterone values. No statistically significant changes were found with respect to liver tryptophan pyrrolase activity.

Daily variation in rat liver tyrosine transaminase activity.

Daily Variation in Rat Liver Tyrosine Transaminase Activity Get access Nutrition Reviews, Volume 27, Issue 11, November 1969, Pages 323–325, https://doi.org/10.1111/j.1753-4887.1969.tb03663.x Published: 01 November 1969

Regulation of the kinetic behavior of serine dehydratase and tyrosine aminotransferase during the development of rainbow trout ( Oncorhynchus mykiss)

Serine dehydratase (SerDH) and tyrosine aminotransferase (TyrAT) are regulatory enzymes of serine and tyrosine catabolism in trout. Here, we have studied the kinetic behavior of SerDH and TyrAT in liver and white muscle of rainbow trout ( Oncorhynchus mykiss) at different stages of development (fingerling: 14-week-old trout; juvenile: 24-, 28-, 40-week-old trout; adult: 96-week-old trout). SerDH and TyrAT showed hyperbolic kinetics in all developmental stages. A significant and progressive decrease in the specific activity, maximum velocity and catalytic efficiency of hepatic SerDH and hepatic and white-muscle TyrAT was observed during development. Nevertheless, the specific TyrAT activity per cell unit was similar in the fingerling and adult stages. No significant changes were found in the Michaelis constant of the different groups of age. This behavior is consistent with the existence of a regulation of the number of enzyme molecules. Total TyrAT activity was of similar magnitude in liver and in white muscle in the fingerling and adult stages. These results show that, in trout, SerDH and TyrAT are two inducible enzymes regulated by the development that showed their highest levels during the first stages, in which the highest whole-body growth rate was found. These results imply high serine and tyrosine requirements in fingerling and juvenile stages that should be considered in the formulation of trout diet for these stages.

Mechanism of Liver Tyrosine Aminotransferase Increase in Ethanol-Treated Mice and Its Effect on Serum Tyrosine Level

Liver tyrosine aminotransferase (TAT) activity is known to increase with ethanol treatment; however, the mechanism of this increase is unclear. Upon investigation we found that TAT activity and mRNA levels started to increase 2 h after ethanol administration and continued to increase until 6 h after ethanol administration. The increase in ethanol-induced TAT activity could not be explained by calorie loading after fasting, since ethanol loading increased TAT expression, while glucose loading decreased TAT expression. In addition, liver TAT activity was not related to serum tyrosine levels. TAT activity increased when an adenosine A2 agonist, 5'-N-ethylcarboxamide adenosine, was given. Since TAT activity is increased by cAMP, and ethanol increases cAMP production via an adenosine receptor-dependent mechanism, this increase in ethanol-induced TAT activity may occur via an adenosine receptor-dependent mechanism.

Illuminating the interrelated immune and endocrine adaptations after multiple exposures to short immobilization stress by in vivo blocking of IL-6

Intermittent psychological stress was induced in adult rats by 2 h/day of immobilization stress for 4 days, with or without blocking the function of IL-6 by using an anti-IL-6 antibody. Basal concentrations of serum corticosterone, IL-1beta, IL-6, and TNF-alpha were assessed 24 h after the last intervention, as were levels of glucocorticoid receptors (GR) and activities of glucocorticoid-inducible enzymes (tyrosine aminotransferase and glutamine synthetase) in muscle and liver. Whole blood cultures were used to assess both spontaneous and LPS-induced reactivity of peripheral blood mononuclear cells. Stress increased corticosterone concentration in a manner partially modulated by IL-6. Serum IL-1beta concentration was downregulated during stress when IL-6 was blocked (P < 0.01). LPS-induced IL-6 secretion by peripheral blood mononuclear cells in vitro correlated positively with serum IL-1beta concentration in antibody-treated groups, independently of stress (R = 0.70 in nonstressed and R = 0.78 in stressed rats; both P < 0.05), whereas serum corticosterone concentration correlated positively with LPS-induced secretion of IL-6 only in control rats (R = 0.66; P < 0.05). Reductions in liver GR levels indicated independent effects of stress (34.5%) and anti-IL-6 antibody (16.7%) and additive effects for both (62.5%). Similar results are reported for vastus muscle. Conversely, stress increased tyrosine aminotransferase and glutamine synthetase activities in muscle and liver with a significant (P < 0.05) effect of anti-IL-6 antibody only seen in stressed livers. In conclusion, IL-6 plays a role in maintaining circulating IL-1beta concentration after multiple exposures to stress, thus promoting a continued elevation of corticosterone release; in peripheral tissues, IL-6 antagonizes the effects of glucocorticoids, especially at the level of GR concentration.

Mercury influences rat liver tyrosine aminotransferase activity and induction by dexamethasone

The effects of mercury (Hg) on basal and dexamethasone-induced tyrosine aminotransferase (TAT) activity in rat liver were studied. Comparison of TAT activity after in vitro and in vivo mercury application revealed the influence of the metal only when applied in vivo, suggesting that the effects are expressed at the level of TAT gene transcription. Intraperitoneal administration of mercury at 1, 2 or 3 mg Hg kg(-1) b.w. 4 h before decapitation was shown to stimulate the basal activity of TAT. The most prominent increase was observed 4 h after the metal administration. When applied at 1 and 2 mg Hg kg(-1) b.w. mercury was also shown to reduce partially the extent of the enzyme induction by dexamethasone, which was injected intraperitoneally at 5 mg kg(-1) b.w. 5 h before death. The highest dose of mercury (3 mg Hg kg(-1) b.w.) almost completely abolished the dexamethasone effect. The finding that mercury increases basal activity of the enzyme while decreasing its induction by dexamethasone suggests that stimulatory effects of this metal on TAT activity are probably mediated by factors other than glucocorticoids.

Inhibition of glucocorticoid receptor binding by nitric oxide in endotoxemic rats*

Nitric oxide is an important participant in septic shock. For example, it causes profound vasodilation and hypotension. Despite their potent antiinflammatory properties, glucocorticoids are not routinely used in septic shock. Some studies show that antiinflammatory doses of glucocorticoids can be beneficial, but other studies do not indicate their use in this situation. We have previously shown the inhibitory effect of nitric oxide on glucocorticoid receptor binding in vitro. Nitric oxide donors decreased the binding of immunoprecipitated glucocorticoid receptor obtained from mouse L929 fibroblasts. These in vitro findings prompted us to study whether in vivo manipulations of the nitric oxide system would interfere with the glucocorticoid receptor binding. Prospective, experimental study. Research laboratory at a university. Female Wistar rats. Injection of bacterial lipopolysaccharide, anesthesia, cardiovascular perfusion, and organ removal for biochemical assays. Following lipopolysaccharide injection, plasma nitrate + nitrite increased and inducible nitric oxide synthase activity was stimulated in several organs, the highest rates being in the lung and spleen. If dexamethasone was injected before lipopolysaccharide, it completely blocked inducible nitric oxide synthase induction and the increase in plasma nitrate + nitrite. On the other hand, if dexamethasone was injected after lipopolysaccharide, it failed to affect both inducible nitric oxide synthase induction and increased plasma nitrate + nitrite levels. Lipopolysaccharide also caused an inhibition of glucocorticoid receptor binding in lung and spleen. Previous administration of a nitric oxide synthase inhibitor prevented both lipopolysaccharide-induced decrease in glucocorticoid receptor binding and the increase in plasma nitrate + nitrite. Injection of a nitric oxide donor into naive animals significantly decreased glucocorticoid receptor binding activity and prevented dexamethasone-induced increase in liver tyrosine aminotransferase activity. The results indicate that the failure of glucocorticoids to exhibit their antiinflammatory effects when administered to endotoxemic rats may be explained, at least in part, by the nitric oxide-induced inhibition of glucocorticoid receptor binding ability, thus precluding the expression of the antiinflammatory effects of both exogenous and endogenous corticosteroids.

Relationship between high sensitivity of suckling mice to hepatocarcinogenic and antiglucocorticoid effects of o-aminoazotoluene and diethylnitrosamine.

Suckling mice were more sensitive to the hepatocarcinogenic effect of various carcinogens compared to adult animals. After treatment with o-aminoazotoluene and diethylnitrosamine HNF3-DNA-binding capacity and glucocorticoid-induced liver tyrosine aminotransferase activity in suckling mice decreased more significantly than in adult animals.

Rat liver tyrosine aminotransferase activity and induction by dexamethasone upon cadmium intoxication

This study was focused on Cd effects on basal and dexamethasone-induced tyrosine aminotransferase (TAT) activity in the rat liver cytosol. Cadmium (Cd), applied in the dose of 2 mg/kg b.w., stimulated both TAT activity and its induction by dexamethasone, inducing the most prominent alterations 24 h after administration. Doses lower than 2 mg Cd/kg b.w. were ineffective while the higher ones (3 and 4 mg Cd/kg b.w) led to the changes similar to those reached by 2 mg Cd/kg. The in vitro application of different Cd concentrations to the liver cytosol rendered the enzyme activity unchanged suggesting that the metal acted at the level of TAT gene transcription.

Contrasting effects of acute and chronic ethanol administration on rat liver tyrosine aminotransferase

We compared the effects of acute and chronic ethanol administration on the activity and synthesis of tyrosine aminotransferase (TAT) in rat liver. In acute experiments, chow-fed rats received a single dose of either ethanol (6 g/kg body wt.) or saline. In chronic studies, rats were pair-fed liquid diets containing either ethanol (36% of calories) or isocaloric maltose-dextrin for 6–8 weeks. In rats acutely fed ethanol, the relative rate of TAT synthesis was more than twofold higher than in saline-treated controls. In rats subjected to chronic ethanol administration, both the TAT activity and synthesis rate were the same as in pair-fed controls, but both these parameters in the two groups were equal to those in animals given acute ethanol acutely. These findings indicate that whereas acute ethanol administration was associated with a stimulation of TAT synthesis, long-term ethanol administration was not. The data suggest that ethanol itself does not directly induce TAT. Rather, enzyme synthesis is regulated by one or more endogenous secondary effector(s) whose production is influenced differently by acute or chronic ethanol feeding.

Correlation between the effects of retinoic acid and dexamethasone on liver tyrosine aminotransferase

A single dose of 50 μg of trans-retinoic acid administered to rats significantly raised the level of hepatic tyrosine after a few hours. This effect was compared with that of dexamethasone and a possible correlation between these effectors was also investigated. An equal increase in enzyme activity level caused by retinoic acid was observed in adrenalectomized rats, leading to the suggestion that the effect of retinoic acid on liver tyrosine aminotransferase is independent of glucocorticoids. However, the study of the binding activity of the liver nuclear glucocorticoid receptors vs dexamethasone showed that this activity is favoured by retinoic acid, whereas no variation was evidenced for retinoic acid receptors caused by dexamethasone. In the adrenalectomized rat, the synergistic effect produced by the association of retinoic acid and dexamethasone at the lowest doses used led us to conclude that retinoic acid is an efficient effector of liver tyrosine aminotransferase. It probably affects tyrosine aminotransferase activity in a dependent and an independent way, regulated respectively by the glucorticoid status and by the provision of retinoic acid.

Differences in binding of hepatic nuclear proteins from lean and obese rats to the 5'-upstream region of tyrosine aminotransferase.

The glucocorticoid effects on liver tyrosine aminotransferase mRNA levels have been studied in young, lean, and obese Zucker (fa/fa) rats and 5'-upstream regions of the tyrosine aminotransferase (TAT) gene have been used in gel retardation studies to investigate nuclear protein binding. Hepatic TAT mRNA levels were increased in obese fa/fa rats but were normalized seven days after adrenalectomy. Corticosterone replacement to adrenalectomized rats restored the increased levels of TAT mRNA in the obese animals. A 60-bp fragment of upstream TAT DNA (-2463 to -2403) was identified which showed higher levels of band shifting after incubation with hepatic nuclear proteins of obese rats compared with the proteins from lean animals. This differential level of gel retardation was substantially reduced by alkaline phosphatase treatment of nuclear proteins. Gel retardation was reduced when nuclear proteins were prepared from adrenalectomized obese rats, and increased with nuclear proteins from adrenalectomized rats replaced with corticosterone. DNA affinity chromatography and gel electrophoresis identified three proteins of approximately 58, 62, and 65 kDa in the DNA-protein complex. Increased amounts of these three proteins were purified from nuclei of obese rats. HNF3 alpha antibodies induced hypershift of the gel retardation pattern implicating HNF3 alpha as one of the proteins that binds to the 60 bp DNA fragment. The data support the hypothesis that decreased phosphorylation of nuclear proteins in obese rats is glucocorticoid-dependent and may contribute to the altered transcriptional activity of glucocorticoid-responsive genes.

Importance of cholinolytic drug selection for the efficacy of HI-6 against soman in rats

The influence of cholinolytic drugs (atropine, benactyzine, biperiden) on the efficacy of the oxime HI-6 (1-[[[(4-aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydroxyimino)methyl]pyridinium dichloride monohydrate) on soman-induced anticholinesterase and stressogenic effects was studied in rats. Soman-induced acetylcholinesterase inhibition in blood and diaphragm and the stressogenic effects of soman, i.e. an increase in plasma corticosterone level and liver tyrosine aminotransferase activity, were more significantly diminished by HI-6 in combination with benactyzine or biperiden in comparison with HI-6 plus atropine. These findings support a hypothesis that benactyzine as well as biperiden can increase the efficacy of the oxime HI-6 in comparison with atropine. They demonstrate the importance of cholinolytic drug selection in the treatment of soman poisoning in rats.