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)

Twenty-one infants who were candidates for TPN because of respiratory disease were randomized into experimental (TPN) and control (glucose-electrolyte) groups. Serum GOT, GPT, GGTP, 5' nucleotidase, total, direct, and conjugated (ethyl anthranilate-reactive) bilirubin, and bile salt concentrations were determined at entry into the study and at one week. One week of TPN caused significant elevations of GGTP, 5'-N and EA bilirubin values, whereas SGOT, SGPT, SBS, and total and direct bilirubin were unaffected. Addition of a lipid infusion to TPN did not alter these differences. These data are interpreted as showing: (1) amino acid infusion has an early effect on hepatic function which is independent of the many diseases for which this therapy is used and of the concomitant use of lipid; (2) the initial effect appears to be on the canalicular membrane; and (3) the sinusoidal membrane is apparently unaffected by one week of TPN.
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PMID:The effect of short-term total parenteral nutrition on hepatic function in the human neonate: a prospective randomized study demonstrating alteration of hepatic canalicular function. 611 1

Methotrexate-loaded glutaraldehyde-treated canine carrier erythrocytes were used to deliver a 1.6-mg/kg dosage of drug. About 90% of the drug-loaded cells disappeared from circulation within 1 h. Approximately 11 mg of drug reached the liver, and a substantial portion of the methotrexate entered the enterohepatic bile salt circulation. Biochemical tests of liver function, such as alkaline phosphatase and serum glutamine pyruvate transaminase, indicated mild hepatocellular necrosis which was attributed to the action of methotrexate on the hepatocytes. Bilirubin levels were unchanged during and following drug treatment. The plasma half-life of the drug was extended 2.4-fold in the first 24 h following injection.
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PMID:Hepatic pharmacokinetics of glutaraldehyde-treated methotrexate-loaded carrier erythrocytes in dogs. 641 45

To evaluate the potential role of taurine deficiency in the pathogenesis of parenteral nutrition-induced cholestasis, 20 premature (less than 34 weeks AGA) infants were randomized to receive parenteral nutrition with and without taurine (10.8 mg/kg/day) during the first 10 days of life. Birth weight, gestational age, and protein and caloric intake were similar in both groups. Plasma taurine levels and hepatic function were assessed before the study began (3 +/- 1 days of age), at 5 +/- 1 days of age, and at 9 +/- 1 days of age. Although plasma taurine levels were significantly greater at 5 +/- 1 and 9 +/- 1 days of age (p = 0.009) in the group receiving supplementation, no differential effect on hepatocellular function could be detected during this short period of time. A decrease in plasma ammonia (p = 0.001), alanine aminotransferase (ALT) (p = 0.036), gamma-glutamyltranspeptidase (GGTP) (p = 0.05), 5'-nucleotidase (5'N) (p = 0.001), and bile salt concentrations was noted in both groups, indicating the rapid maturation of hepatic function even in the presence of parenteral nutrition during the first 10 days of life.
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PMID:Effect of taurine supplementation on hepatic function during short-term parenteral nutrition in the premature infant. 642 96

Treatment of rats with nifurtimox, a nitrofuran derivative widely used for the treatment of Chagas' disease, induced a time- and dose-dependent depletion of liver glutathione, maximal effects being obtained with 200 mg nifurtimox/kg body weight. Extra release of both oxidized (GSSG) and reduced (GSH) glutathione into bile contributed to this depletion. Glutathione excretion into bile accounted for only part of liver glutathione loss, thus indicating that, in addition to the GSH-peroxidase reaction (resulting in GSSG generation), other glutathione-related processes were involved in nifurtimox detoxification. Bile flow, bile salt excretion, liver lipid conjugated diene content, liver glutathione reductase and glutathione peroxidase activities, and serum alanine aminotransferase (ALAT) activity were not affected by the nifurtimox treatment, thus ruling out widespread damage of the liver cell by nifurtimox. Nevertheless, the extra GSH release in the nifurtimox-treated rats may indicate an alteration of the hepatocyte membrane.
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PMID:Increased biliary secretion and loss of hepatic glutathione in rat liver after nifurtimox treatment. 684 98

Treatment of male Wistar rats with a single dose of lead nitrate caused a marked enlargement of the liver, which reached its maximum 3 days after the administration of the metal salt. This grossly anatomic effect was accompanied by biochemical changes such as an increase in total protein and DNA content, with a maximum at 3 and 4 days, respectively. A partial regression of liver weight and total DNA and protein content occurred 7 days after lead administration; a significant increase in DNA concentration was found after 1 week, while no variation in protein, when expressed as milligrams per gram liver, was observed in lead-treated rat liver. An increase in DNA synthesis, as monitored by the incorporation of labeled thymidine, was also observed. An enhancement in the specific radioactivity of DNA was evident at 24 hours and appeared maximal at 36 hours after the administration of lead nitrate. The ability of lead to stimulate liver cell proliferation was shown by a significant increase of cells entering mitosis, with a peak at 48 hours. This mitogenic stimulus occurred in parenchymal as well as in nonparenchymal cells, thus showing that this effect was not unique to a particular liver cell populations. No detectable cell necrosis, as monitored by histologic observation, was seen in the liver of lead-treated rats, thus indicating that the cellular proliferation induced by lead is not due to a regenerative response. Only a slight elevation in the levels of serum glutamate-pyruvate transaminase (GPT) was observed by biochemical analysis.
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PMID:Liver cell proliferation induced by a single dose of lead nitrate. 684 73

Cefazolin given sc to male rats in daily doses of 0.5-2 g per kilogram of body weight significantly decreased alanine aminotranferase activity in serum, liver, kidney, heart, and brain 2-4 wk from the beginning of the treatment. Serum aspartate aminotransferase was also reduced, but serum alkaline phosphatase and tissue pyruvate decarboxylase activities remained unaltered. In female rats, daily sc administration of cefazolin at 0.1-1 g/kg also brought about a dose-related reduction of alanine and aspartate aminotransferase activities, which reached statistical significance at high dose levels. The effect of cefazolin at low concentrations was partly reversed by administration of pyridoxal in vivo. Paradoxically, at higher dose levels pyridoxal potentiated the action of cefazolin on serum aminotranferases. The low enzyme activities were elevated by subsequent addition of pyridoxal 5'-phosphate in vitro. Similar results were obtained when rats were treated with isoniazid at daily oral doses of 200 mg/kg; administration of pyridoxal completely restored alanine aminotransferase activity to the normal level within 2 wk. Cefazolin was metabolized in vivo, resulting in some metabolites that probably possessed a hydrazine group, since positive reactions were obtained with p-dimethylaminobenzaldehyde and Fast Blue B salt. The potentiation of decreased aminotransferase activity by pyridoxal indicated, however, some dissimilarity in the effect between isoniazid and cefazolin.
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PMID:Effect of cefazolin on aminotransferase activity in the rat. 728 5

Altered hepatic secretory function after orthotopic liver transplantation constitutes a major perioperative clinical problem. Cholestasis and cholesterol gallstone formation are among the most frequent complications reported. Such changes in the allograft secretory function can be secondary to many factors like graft injury due to preservation and marked rejection, surgical complications, immunosuppressive therapy, and sepsis. The effects of liver transplantation per se on bile formation and biliary lipid secretion are unknown. The rat model of orthotopic liver transplantation was used to characterize better the true effect of transplantation without the influence of these confounding variables. Twenty-four-hour bile collections were performed on nine transplanted versus nine liver-denervated (sham) rats 4 weeks after surgery, and nine normal Sprague-Dawley rats. The liver allografts showed mild lymphocytic infiltration in portal tracts and the serum alanine transaminase levels were not significantly elevated. Bile flow and the secretion of bile salts and bilirubin under basal conditions were unchanged. Bile salt pool size, synthesis rate, and bile acid composition did not differ among the three groups. However, cholesterol secretion was dramatically reduced (50%) in the transplanted rats and decreased 31% in the liver-denervated rats (P < .001 and .01, respectively), resulting in a more favorable cholesterol saturation index (CSI = 0.29 for transplanted and 0.32 for sham versus 0.45 for normal controls; P < .01). Thus, liver transplantation with its attendant denervation did not impair hepatic secretory function, but rather improved biliary lipid composition despite mild rejection.
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PMID:Effects of liver transplantation on bile formation and biliary lipid secretion in the Sprague-Dawley rat. 755 78

The hepatoprotective effect of the shark bile salt 5beta-scymnol has been studied in the model of acute hepatotoxicity induced by administration of acetaminophen (APAP, paracetamol). 5beta-Scymnol at doses of 20, 35, and 70 mg/kg intraperitoneally (ip) decreased significantly the serum activity of alanine aminotransferase, sorbitol dehydrogenase, and lactate dehydrogenase (p < 0.05) caused by APAP treatment (350 mg/kg ip) alone. The highest dose of 5beta-scymnol remained hepatoprotective when administered 4 hr after the APAP overdose. N-Acetylcysteine (NAC) is protective against APAP-induced hepatotoxicity at 250 and 500 mg/kg (ip) when administered up to 3 hr after APAP overdose, as shown by a significant reduction in serum enzyme activity. Coadministration of 5beta-scymnol (70 mg/kg) and NAC (250 mg/kg) also reduced serum enzyme levels and histopathological effects; however, a similar level of hepatoprotection was conferred by 5beta-scymnol treatment alone. In addition, 5beta-scymnol has potent hydroxyl radical quenching activity as it markedly inhibited deoxyribose degradation in a ferrous/ascorbate Fenton reaction system. These results indicate a possible role for the use of 5beta-scymnol, either alone or concomitant with NAC, in the prevention of hepatic necrosis following toxic doses of APAP.
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PMID:Hepatoprotective effects of the shark bile salt 5beta-scymnol on acetaminophen-induced liver damage in mice. 881 14

Recent studies have demonstrated that nitric oxide (NO) acts as a pulmonary vasodilator when inhaled in low concentrations. Due to the physicochemical similarities between NO and carbon monoxide (CO), it was speculated that low concentrations of CO would have similar effects in the isolated rat lung. The purpose of this study was to determine the role of CO (200 and 1000 ppm) in modulating hypoxia- and angiotensin II (AII)-induced pulmonary vasoconstriction, using isolated salt-perfused lungs of normotensive (CON) or pulmonary hypertensive male rats. Pulmonary hypertensive rats (ALT), induced by simulated altitude exposure (4572 m; 430 mm Hg for 32-48 days), were studied to determine the actions of low-dose CO in a remodeled pulmonary vascular bed. Right ventricular hypertrophy and polycythemia were evident in the ALT rats, suggesting that simulated altitude exposure induced pulmonary hypertension and consequent pulmonary vascular remodeling. CO did not significantly affect pulmonary vascular responses to acute hypoxia (6% CO2, balance N2) in either CON or ALT rats. There were also no significant differences in pulmonary pressor responses to AII injections (0.2 or 0.4 micrograms) in CON or ALT lungs either immediately following or during an acute hypoxia + CO exposure. Therefore, acute low-dose CO exposure (< 1000 ppm) does not appear to attenuate pulmonary vasoconstriction in isolated rat lungs.
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PMID:Low-dose carbon monoxide does not reduce vasoconstriction in isolated rat lungs. 883 33

Forms of 2,4-dichlorophenoxyacetic acid (2,4-D) are herbicides used in the control of a wide variety of broadleaf and woody plants. Subchronic toxicity studies in dogs were conducted on three forms of 2,4-D: the parent form, 2,4-D acid (ACID); 2,4-D dimethylamine salt (DMA); and 2,4-D 2-ethylhexyl ester (2-EHE). The three studies were designed to allow for comparison of the toxicity of the three forms. Doses in the subchronic studies, on an acid equivalent basis, were 0, 0.5 (ACID only), 1.0, 3.75, and 7.5 mg/kg/day. Treatment related findings in the three studies included reductions in body weight gain, and food consumption, and minor increases in blood urea nitrogen, creatinine, and alanine aminotransferase. The data from the three subchronic studies demonstrated the comparable toxicity of ACID, DMA, and 2-EHE and support a subchronic no observed adverse effect level (NOAEL) of 1.0 mg/kg/day for all three forms. Due to the similarity in toxicity of the three forms of 2,4-D, a 1-year chronic toxicity study was performed on the parent ACID to fully characterize the potential toxicity of 2,4-D in the dog. ACID was well tolerated at doses of 0, 1.0, 5.0, and 7.5 mg/kg/day. The clinical pathology alterations were similar to those seen in the subchronic studies and were not progressive. The histopathology alterations observed were not severe in nature and the no observed effect level in the chronic study was determined to be 1.0 mg/kg/day. There was no indication of any immunotoxic or oncogenic response in the studies. In conclusion, the findings of these studies indicate comparable toxicity among representative forms of 2,4-D and their generally low toxicity following subchronic and chronic dietary exposure in the dog.
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PMID:Comparative subchronic and chronic dietary toxicity studies on 2,4-dichlorophenoxyacetic acid, amine, and ester in the dog. 883 42


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