Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estradiol-implanted (EB) and sham-operated (SB) male rats (100-120 g Fody wt) were kept on a vitamin B6-deficient diet for 1 month along (Formula: see text) with their respective estradiol pair-fed (EPF) and sham-operated pair-fed (SPF) controls. Pyridoxine-deficient animals had higher kidney weights and increased activities of liver glycolic acid oxidase (GAO) and glycolic acid dehydrogenase (GAD) as compared to their pair-fed control animals. Kidney weights, GAO, and GAD levels in these animals are negatively correlated with erythrocyte alanine transaminase (EALT) levels, indicating that pyridoxine status regulates these two major enzymes of oxalate biosynthesis. Estradiol-treated animals showed a lower reduction in EALT levels after feeding them a pyridoxine-deficient diet for 1 month as compared to untreated animals. Estradiol administration decreased GAO levels in both normal and pyridoxine-deficient animals.
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PMID:Effect of estradiol on the oxalate metabolism in vitamin B6-deficient male rats. 639 78

Four trials involving 192 Large White X Landrace pigs were conducted to investigate the effect of wide variation of dietary methionine, lysine and caloric density on the activity of hepatic glutamate-oxalate ad glutamate-pyruvate transaminases. Results of the study show that: The activities of the two transaminases were influenced by the nutritional treatments. GOT and GPT activity exhibited significant positive and negative quadratic relationship respectively with dietary methionine levels. Both GOT and GPT activities decreased with increasing caloric density or palm oil level of the diet. In weanling pigs, both GOT and GPT exhibited significant negative quadratic relationship with dietary lysine levels and were also significantly influenced by the sex of the animals. In older pigs, only GOT activity was significantly affected by dietary lysine levels. The correlation of GOT and GPT activities to dietary essential amino acids shows that hepatic enzymatic activities could be good indices of essential amino acid utilization.
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PMID:Liver glutamate-oxalate transaminase and glutamate-pyruvate transaminase activity in pigs as influenced by dietary methionine and lysine levels. 678 54

A combined supplement of magnesium oxide (300 mg/day) and pyridoxine.HCl (10 mg/day) was given p.o. to 16 recurrent calcium oxalate (CaOx) stone formers, and its therapeutic efficacy was biochemically evaluated by measuring various parameters of blood (Na, K, Mg, urea, creatinine, calcium, phosphate, uric acid, alanine transaminase, aspartate transaminase and alkaline phosphatase) and urine (volume, pH, creatinine, Na, K, Mg, uric acid, calcium, phosphate, oxalate and citrate) at 0, 30, 60, 90 and 120 days of treatment. Serum Mg significantly (P < 0.01) increased after 30 days of treatment and remained constant thereafter while other blood parameters were unaltered. Combined treatment led to a significant increase in the urinary excretion of Mg and citrate over pretreatment values while oxalate excretion showed a gradual and significant decline during the therapy. The results confirmed the efficacy of MgO-pyridoxine supplementation in terms of changes in urinary excretion of lithogenic and inhibitory components, leading to a significant (P < 0.01) decrease in CaOx risk index from 0.09 +/- 0.04 at 0 day to 0.05 +/- 0.02 after 120 days of treatment.
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PMID:Effect of combined supplementation of magnesium oxide and pyridoxine in calcium-oxalate stone formers. 799 61

Male weanling rats were maintained on magnesium-deficient diet for 30 d and compared with pair-fed control rats fed magnesium-supplemented diet. Magnesium deficiency led to slow growth and finally to a significant decrease in body weight (P < 0.001) accompanied by a significant hypomagnesaemia, hypomagnesuria and hyperoxaluria (P < 0.001 in each case) in experimental rats as compared to the control rats. Magnesium deficiency altered the glyoxylate metabolism in the liver and kidney mitochondria by significantly decreasing glyoxylate oxidation (by 26 per cent in liver and 17 per cent in kidney) and activity of alpha-ketoglutarate:glyoxylate carboligase enzyme (by 35 per cent in liver and 27 per cent in kidney) in the experimental animals. A significant increase in the specific activities of glycolic acid oxidase (P < 0.001) and glycolic acid dehydrogenase (P < 0.01) and a significant decrease in alanine transaminase (P < 0.01) was also observed in magnesium-deficient rats. No change in liver and kidney lactate dehydrogenase was observed. Thus magnesium deficiency in rats leads to accumulation of glyoxylate in the tissues, a part of which is converted into oxalate, thereby promoting hyperoxaluria.
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PMID:Oxalate metabolism in magnesium-deficient rats. 827 58

Inadvertent ingestion of thiafentanil oxalate by a captive adult female mountain lion (Puma concolor) caused a prolonged clinical syndrome that included sedation and depression, muscle tension, and myopathy that was incompletely antagonized by naltrexone HCl. A serum chemistry profile revealed markedly elevated creatinine phosphokinase (CK; 490,450 IU/l), alanine aminotransferase (ALT; 1,896 IU/l), and aspartate aminotransferase (AST; 4,321 IU/l) 2 days after onset. The affected animal's condition gradually improved over the next 15 days in response to supportive therapy that included diazepam (5 mg as needed), Normasol R (3 l/day), dexamethasone (tapering dose starting at 1 mg/kg), and ketoprofen (1 mg/kg). She eventually recovered completely. Based on these observations, carcasses of animals immobilized with thiafentanil should be marked and disposed of properly to preclude opportunities for secondary exposure and potential intoxication in scavenging species. In addition, caution is advised when using thiafentanil in animals that could be preyed upon before full metabolism of the drug.
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PMID:Suspected secondary thiafentanil intoxication in a captive mountain lion (Puma concolor). 1645 79

This paper reports a comparative study of the antioxidative effects of black and green tea extracts in sodium oxalate-challenged rats. A dose of 10 mg/kg of body weight of sodium oxalate was used to induce lipid peroxidation in vivo. Rats treated with sodium oxalate had 42.06 +/- 3.10 nM/hour, 45.39 +/- 9.75 mg/100 mL, 10.95 +/- 1.52%, 15.95 +/- 3.19 mg/dL, 112.25 +/- 5.15 mg/dL, 59.21 +/- 2.95 IU, 39.55 +/- 2.51 IU, and 150.62 +/- 9.62 KA/unit for serum levels of malondialdehyde, reduced ascorbic acid, catalase, cholesterol, phospholipid, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), respectively. These values are significantly (P < .05) different from values obtained from normal rats. Rats pretreated with 100 mg/kg of body weight of green tea had 27.59 +/- 3.56 nM/hour, 79.11 +/- 5.13 mg/100 mL, 4.23 +/- 0.36%, 50.09 +/- 5.24 mg/dL, 97.58 +/- 4.73 mg/dL, 23.10 +/- 1.59 IU, 31.14 +/- 1.26 IU, and 96.48 +/- 2.36 KA/unit for serum levels of malondialdehyde, reduced ascorbic acid, catalase, cholesterol, phospholipid, AST, ALT, and ALP, respectively, compared with 37.28 +/- 2.07 nM/hour, 72.62 +/- 2.10 mg/100 mL, 6.23 +/- 1.52%, 37.25 +/- 2.84 mg/dL, 78.05 +/- 2.36 mg/dL, 36.08 +/- 1.80 IU, 29.00 +/- 3.02 IU, and 109.23 +/- 6.32 KA/unit recorded for the same parameters in rats treated with black tea. The cholesterol to phospholipid ratio was increased from 0.14 +/- 0.04 in control rats to 0.47 +/- 0.02 and 0.51 +/- 0.01 by black and green tea extracts, respectively. These results suggest that tea extracts have antioxidant properties and that green tea extract is more potent.
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PMID:Studies of the antioxidative effects of green and black tea (Camellia sinensis) extracts in rats. 1765 Oct 72

Nephrolithiasis has a multifactorial origin, and several disorders may coexist in the same patient. We made a basic and a specific laboratory evaluation. The complete metabolic evaluation consisted of a serum chemistry panel: blood sugar level, complete hemogram, serum electrolytes, GOT, GPT, calcium, phosphate, uric acid, and creatinine levels and RIA dosage of PTH, vitamin D3, cAMP, FT4, FT3 and TSH. The complete analyses of random urinalysis and culture are: (1) dip-stick test: pH, leukocytes/bacteria and Brand's test, and (2) 24-hour urine collection: calcium, magnesium, oxalate, phosphate, citrate, urea, urate, sodium, creatinine, chloride, potassium. It is possible with these tests to identify secondary causes of nephrolithiasis and uncover coexisting problems that may have an impact on patient management. The future for diagnosis, prevention and therapy will be the identification of genetic alterations and related specific dosage.
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PMID:Laboratory assessment. 1772 48

Kidney stones are known to haunt humanity for centuries and increase in oxalate is a predominant risk factor for stone formation. The present study was initiated with a notion to study the oxidative and nitrosative stress on erythrocytes under oxalate stress and the putative role of sulphated polysaccharides. Hyperoxaluria was induced in two groups by the administration of 0.75% ethylene glycol in drinking water for 28 days and one of them was treated with sulphated polysaccharides from Fucus vesiculosus from the 8th day to the end of the experimental period of 28 days at a dose of 5 mg/kg body weight subcutaneously. Control and drug control (sulphated polysaccharides alone) were also included in the study. Glycolic and glyoxylic acid levels of urine were analyzed as an index of hyperoxaluria. The plasma enzymic markers of cellular integrity, redox status of red blood cells, osmotic fragility, and (14)C-oxalate binding were investigated. Urine and plasma nitric oxide metabolites, expression of inducible nitric oxide synthase protein, and mRNA were assessed in kidney to evaluate the nitrosative stress. Increased levels of glycolic and glyoxylic acid in urine indicated the prevalence of hyperoxaluria in ethylene glycol-administered groups. Plasma aspartate and alanine transaminase were not altered, but alkaline phosphatase and lactate dehydrogenase of hyperoxaluric group were increased indicating tissue damage. Activities of antioxidant enzymes were decreased, whereas erythrocyte membrane lipid peroxidation was increased in hyperoxaluric rats. Moreover, an altered fragility with an increase in oxalate binding activity was observed in hyperoxaluric group. Increase in nitric oxide metabolites levels in urine and plasma along with an increase in expression of inducible nitric oxide synthase protein and mRNA in kidney were observed in hyperoxaluric rats. Administration of sulphated polysaccharides to hyperoxaluric rats averted the abnormal increase in urinary glycolic and glyoxylic acid levels and enzyme activities, decreased lipid peroxidation, and increased the activities of antioxidant enzymes. Furthermore, increased nitrosative stress accompanying hyperoxaluria was also normalized on sulphated polysaccharides treatment. To conclude, sulphated polysaccharide administration was able to maintain the integrity of erythrocyte membrane and decrease the damage to erythrocytes in hyperoxaluria.
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PMID:Effect of sulphated polysaccharides on erythrocyte changes due to oxidative and nitrosative stress in experimental hyperoxaluria. 1837 35

PH1 (primary hyperoxaluria type 1) is a severe inborn disorder of glyoxylate metabolism caused by a functional deficiency of the peroxisomal enzyme AGXT (alanine-glyoxylate aminotransferase), which converts glyoxylate into glycine using L-alanine as the amino-group donor. Even though pre-genomic studies indicate that other human transaminases can convert glyoxylate into glycine, in PH1 patients these enzymes are apparently unable to compensate for the lack of AGXT, perhaps due to their limited levels of expression, their localization in an inappropriate cell compartment or the scarcity of the required amino-group donor. In the present paper, we describe the cloning of eight human cytosolic aminotransferases, their recombinant expression as His6-tagged proteins and a comparative study on their ability to transaminate glyoxylate, using any standard amino acid as an amino-group donor. To selectively quantify the glycine formed, we have developed and validated an assay based on bacterial GO (glycine oxidase); this assay allows the detection of enzymes that produce glycine by transamination in the presence of mixtures of potential amino-group donors and without separation of the product from the substrates. We show that among the eight enzymes tested, only GPT (alanine transaminase) and PSAT1 (phosphoserine aminotransferase 1) can transaminate glyoxylate with good efficiency, using L-glutamate (and, for GPT, also L-alanine) as the best amino-group donor. These findings confirm that glyoxylate transamination can occur in the cytosol, in direct competition with the conversion of glyoxylate into oxalate. The potential implications for the treatment of primary hyperoxaluria are discussed.
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PMID:Recombinant production of eight human cytosolic aminotransferases and assessment of their potential involvement in glyoxylate metabolism. 1954 38

Drug safety research is frequently faced with the challenge of the selection of appropriate vehicles for use in in vivo non-clinical safety assessment studies. Reported here are the results of blend Labrasol, Labrafil and Transcutol, [L/L/T, (4/4/2, v/v/v)], excipients used as bioavailability enhancer and solubilizer for poorly water-soluble compounds and tested daily for 4 weeks by oral route in Wistar rats (10/sex/group) at dose volumes of 5, 10 or 20 mL/kg/day and compared to controls given 20 mL/kg/day of 1% (w/v) hydroxyethylcellulose in purified water. L/L/T was broadly well tolerated at 5 mL/kg/day and lethal at 20 mL/kg/day in 1 of 20 rats treated at this level. Changes in appearance and behaviour were observed from 10 mL/kg/day with volume-related incidence, severity and duration. Reduced feed intake observed from 5 (females) or 10 mL/kg/day (males) resulted in low bodyweights for high volume males only (-11% of controls). There was a volume-related induction of hepatic CYP 1A1/2, 2B1/2 and/or 2E1 subfamilies from 5 mL/kg/day, with high liver weight, centrilobular hepatocellular hypertrophy and high ALT, triglyceride and cholesterol serum values at 20 mL/kg/day. Renal tubular dilation in medulla, cortical cell degeneration/necrosis with granular material in adjacent glomerular spaces, crystal deposits in the inner medulla, papilla and/or renal pelvis, and tubular mineralization, associated with proteinuria and calcium oxalate crystalluria, were observed at 20 mL/kg/day as well as vacuolation in the adrenal cortex, with a sex-dependant localization. According to these results, 5 mL/kg/day was considered as an acceptable volume for further use of L/L/T (4/4/2, v/v/v) blend as a vehicle for poorly water soluble drugs in Wistar rat toxicity studies.
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PMID:Assessment of Labrasol/Labrafil/Transcutol (4/4/2, v/v/v) as a non-clinical vehicle for poorly water-soluble compounds after 4-week oral toxicity study in Wistar rats. 2034 7


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