Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of feedstuffs treated with ionizing radiation on the nutrition of dogs was tested in four groups of animals. Two groups were administered for 90 days a ration, the main part of which (VETACAN meat feed mixture and VETAVIT loose feed mixture) was irradiated with radioisotope Co 60 of the intensity of 25 kGy/kg, in other two groups of dogs the nonirradiated ration was used for the same time period. The control groups of dogs were put together for these two diets. The laboratory examination of irradiated feedstuffs confirmed their complete microbiological and mycological intactness. However, the irradiation brought about a significant 35% degradation of essential amino acids with an increase of ammonia nitrogen, destructive changes in the lipid component of feedstuffs and a partial decomposition of the saccharide part of the VETAVIT feed mixture, expressed by the acidity of water extract. The sensory evaluation of irradiated feedstuffs did not show any perceptible alterations. The haematological examination of the blood of animals, which had been administered irradiated feed rations, demonstrated a significant negative influence on the blood picture. The biochemical examination of the blood serum and plasma revealed that total proteins of experimental dogs dropped and the creatinine level was also significantly decreased. Neither was the level of carbohydrate nutrition nor the energy saturation affected by irradiation. The glucose levels in the blood serum of dogs fluctuated within the range of physiological reference values. The growth of free ammoniacal bases of feedstuffs, evoked by ionizing radiation, conditioned obviously the level of actual pH of blood in dogs as determined in this study. The destruction of lipoid fraction in the feedstuffs induced a decrease in the activity of lipophile retinol and thus the biological value of feeds was impaired. The biochemical examination of ALT, AST and ALP enzyme activity did not show any increased activity of parenchyma, in particular of liver cell. A decisive role of the biological quality of feed ration for utilization of some minerals was demonstrated by a significant decrease of the magnesium level in animals administered irradiated feed rations without any biological supplementation. On the contrary, the potassium, calcium and phosphorus levels did not reflect this dietary difference between the groups.
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PMID:[The effect of feeds treated with ionizing irradiation on biochemical indicators of the nutritional value of energy nutrients]. 393 33

Large doses of retinol (vitamin A) have been shown to potentiate the hepatotoxicity of several chemicals in rats. The objective of this study was to determine how retinol would affect the pulmonary and hepatic toxicity caused by 1-nitronaphthalene (1-NN). All-trans-retinol (75 mg/kg/day, po) was administered for 7 days to male Sprague-Dawley rats. One day after the last dose of retinol, animals were given a single injection of 1-NN (100 mg/kg, ip). At 24 hr, animals receiving retinol vehicle and 1-NN exhibited respiratory distress syndrome and chromodacryorrhea. Pulmonary morphological changes included necrosis and exfoliation of the bronchiolar epithelium, as well as infiltration of inflammatory cells into the interstitial areas around affected bronchioles. The bronchioalveolar lavage fluid from these animals exhibited significant increases in the activities of gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), as well as protein and inflammatory cell content. Following pretreatment with retinol, none of the animals treated with 1-NN exhibited outward signs of toxicity. In addition, the lavage fluid of these rats revealed significant reductions in inflammatory cells, protein, and LDH activity. However, lavage fluid GGT activity was significantly increased. Morphological evaluation of the lungs revealed nonciliated bronchiolar epithelial (Clara) cell damage with no associated inflammation. Retinol pretreatment resulted in potentiated hepatotoxicity as indicated by increases in plasma alanine aminotransferase and GGT activities, as well as plasma total bilirubin. The altered plasma enzyme activities correlated with increased hepatocyte and bile duct epithelial necrosis, as well as an increased infiltration of neutrophils into the areas around bile ducts. Retinol potentiation of 1-NN-induced hepatocyte necrosis was significantly reduced following pretreatment with gadolinium chloride (GdCl3). From these experiments, we conclude that in the lung pretreatment with retinol decreased the severity of 1-NN-induced toxicity apparently by an anti-inflammatory mechanism. In the liver, retinol potentiated 1-NN-induced liver injury apparently through a proinflammatory mechanism by activating Kupffer cells and increasing the infiltration of neutrophils into the periportal regions adjacent to bile ducts.
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PMID:All-trans-retinol alteration of 1-nitronaphthalene-induced pulmonary and hepatic injury by modulation of associated inflammatory responses in the male Sprague-Dawley rat. 759 3

The interactive effects between retinol and various hepatotoxicants (allyl alcohol, acetaminophen, carbon tetrachloride, D-galactosamine, and phalloidin) were studied in the male Swiss Webster mouse. The mice were administered retinol at 75 mg/kg/day (or the vehicle of retinol) by oral gavage for 7 days. Hepatoxicity produced by the chemicals was determined by plasma alanine aminotransferase (ALT) activity and histopathology. After 7 days of retinol pretreatment, the hepatotoxicities of allyl alcohol, acetaminophen, and galactosamine were potentiated. Interestingly, the hepatotoxicity of carbon tetrachloride and phalloidin was protected by identical retinol pretreatment. Microscopic examination of histologic liver sections demonstrated the specific hepatic necrosis associated with each individual chemical and confirmed the ALT values obtained. Once an interaction between retinol and the five hepatotoxicants was established, the duration of retinol pretreatment necessary to elicit an interaction was determined for each hepatotoxicant. Results demonstrated that the duration of retinol pretreatment was specific for each hepatotoxicant. The accumulation of retinoids in the liver during retinol pretreatment was determined using high-performance liquid chromatography analysis. Significant increases in the basal liver levels of retinol and retinyl palmitate were seen within 1 to 3 days of retinol treatment compared to control. Retinol pretreatment resulted in potentiation or protection of specific hepatotoxicant-induced liver damage. Currently, studies are being conducted which probe into the mechanisms of these interactions.
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PMID:The interactions between retinol and five different hepatotoxicants in the Swiss Webster mouse. 766 12

Pretreatment of rats with large doses of vitamin A (VA, retinol) has been shown to potentiate carbon tetrachloride hepatotoxicity. The relationship between VA dose or pretreatment duration with VA and the extent of potentiation of CCl4 hepatotoxicity is unknown. Therefore, VA was administered to male SD rats (180-200 g) by oral gavage in daily doses of 100,000, 150,000, 200,000, or 250,000 IU/kg for 3 weeks. In another experiment, rats were given VA in a daily dose of 250,000 IU/kg for 1 day, 1, 2, 3, or 5 weeks. At 24 hr after the last VA dose, CCl4 (0.15 ml/kg, ip) was administered. Hepatotoxicity was assessed by increases in plasma alanine aminotransferase activity and by histological evaluation of the liver. Additionally, the correlation between the hepatic concentration of retinol and retinyl palmitate after VA treatment and the extent of potentiation of CCl4-induced liver injury was studied. In the initial 3-week dose-response study, as the daily dose of VA increased so did the degree of potentiation of CCl4 hepatotoxicity. All treatment durations with VA (250,000 IU/kg per day), except 1 day, resulted in equivalent potentiation of CCl4 hepatotoxicity. VA treatment did not result in elevated hepatic concentration of retinol. However, VA treatment did increase the concentration of retinyl palmitate in the liver (except for the 1-day treatment). No linear correlation could be seen between the hepatic concentration of retinyl palmitate and the extent of VA potentiation of CCl4 hepatotoxicity. VA treatment also potentiated to hepatotoxicity of minimally hepatotoxic doses of acetaminophen, allyl alcohol, and endotoxin. Because these chemicals produce hepatic injury by diverse mechanisms it is concluded that VA potentiates hepatic injury by altering a process involved in the progression of cell injury.
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PMID:Characterization of vitamin A potentiation of carbon tetrachloride-induced liver injury. 848 Mar 37

Pretreatment of rats with large doses of vitamin A (VA) potentiates the hepatotoxicity of CCl4. Because our previous studies indicate that VA treatment does not enhance CCl4 metabolism but does enhance CCl4-induced lipid peroxidation and activates liver Kupffer cells to release increased amounts of oxygen-centered free radicals, the current studies were designed to determine if VA treatment potentiates CCl4-induced liver injury through increased release of reactive oxygen species. Plasma clearance of colloidal carbon, an index of Kupffer cell phagocytic activity, was enhanced two- to threefold in rats treated for 7 days with VA (retinol, 250,000 IU/kg per day). Accordingly, VA treatment alone caused Kupffer cell activation. To determine if these activated Kupffer cells could potentiate hepatic injury through release of reactive oxygen species upon CCl4 challenge, polyethylene glycol coupled-superoxide dismutase (PEG-SOD, 10,000 IU/kg) or -catalase (PEG-CAT, 40,000 IU/kg) was given iv 2 hr after CCl4 (0.15 ml/kg, ip) to control or VA-pretreated rats to quench any released reactive oxygen. PEG-SOD and PEG-CAT effectively blocked VA potentiation of CCl4 liver injury as assessed at 24 hr by change in plasma ALT. Methylpalmitate (MP, 2 g/kg), an inhibitor of Kupffer cell phagocytosis and related oxygen burst, also blocked the potentiation of liver injury when given iv 24 hr before CCl4 to VA-pretreated rats. At the doses used, PEG-SOD or PEG-CAT did not influence CCl4 toxicity in control rats (at 0.15 or 2 ml CCl4/kg). Importantly, SOD, CAT, and MP blocked the enhanced lipid peroxidation induced by CCl4 in VA-pretreated rats. From these findings we conclude that the potentiation of CCl4 liver injury by VA pretreatment is mediated, at least in part, by active oxygen species released from Kupffer cells and possibly other macrophages that are activated by VA. Supporting this conclusion is the failure of VA pretreatment to increase the release of LDH from suspension of hepatocytes incubated with CCl4.
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PMID:Vitamin A potentiation of carbon tetrachloride hepatotoxicity: role of liver macrophages and active oxygen species. 848 Mar 39

Cross-sectional interactions by malaria status were investigated between plasma alpha-tocopherol, retinol, and several carotenoids (lutein, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene) and indicators of disease severity (blood parasite count, hemoglobin concentration), acute-phase response (plasma albumin and ceruloplasmin concentrations), hepatic involvement (plasma alanine aminotransferase), oxidant status and antioxidant status (plasma thiobarbituric acid-reactive material and ascorbate), nutritional (weight-for-age) and carrier protein [retinol binding protein (RBP)] status, and cholesterol concentration (as a proxy for lipoprotein) in 100 consecutively admitted children with malaria. There were 50 children with severe and 50 with mild malaria and 50 age- and sex-matched control subjects. alpha-Tocopherol, retinol, and all the carotenoid concentrations were lower in the patients than in the control subjects (P < 0.001). The differences were greater in severe than in mild malaria, except for lutein. In severe malaria only, both retinol and alpha-tocopherol correlated with albumin, ceruloplasmin, and RBP concentrations whereas in all three groups retinol correlated with RBP and alpha-tocopherol correlated with cholesterol (all P < 0.01)). Using multivariate analysis on data from all patients combined, cholesterol was the most significant factor explaining the variance in alpha-tocopherol (29%) whereas RBP was responsible for 95% of the variance in retinol. Plasma cholesterol and RBP values in turn (in the absence of alpha-tocopherol and retinol, respectively) were influenced primarily by acute-phase markers (mainly albumin and ceruloplasmin). Alanine aminotransferase (r = -0.17) and thiobarbituric acid-reactive material (r = -0.17) also showed a small contribution to the variance of RBP but 60-70% remained unexplained. In conclusion, low plasma lipid-soluble micronutrient concentrations in malaria are strongly influenced by the reductions in their carrier molecules, which, in turn, are low as a consequence of the acute-phase response.
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PMID:Plasma alpha-tocopherol, retinol, and carotenoids in children with falciparum malaria. 866 21

Evidence suggests that 7 days of retinol pretreatment potentiates chemical-induced liver injury by a mechanism that involves activation of Kupffer cells (KC). These studies were designed to determine if shorter dosing regimens of retinol potentiate carbon tetrachloride (CCl4). Initially, a single dose of retinol was shown to potentiate the hepatotoxicity of CCl4. Male Sprague-Dawley rats were pretreated with all-trans-retinol (75 mg/kg p.o.) 24 hr prior to KC isolation or administration of CCl4 (0.2 ml/kg i.p.). KC isolated at 24 hr after retinol released increased amounts of superoxide anion when stimulated with zymosan or phorbol myristate acetate. At 24 hr after CCl4, plasma ALT activities and histological sections of liver were examined. Retinol-pretreated rats showed a significant elevation in both enzyme leakage and centrilobular to midzonal necrosis compared to retinol vehicle controls following CCl4. Although complete protection was not seen, depletion of KC or neutrophils (PMNs) (by gadolinium chloride (GdCl3) or a PMN-depleting antibody, respectively) significantly reduced the hepatotoxicity of 1 day retinol/CCl4 liver injury. Immunohistochemical analysis of livers showed significant elevations in positive staining for ED2, ED1, and HIS48 in retinol-pretreated rats given CCl4. GdCl3 effectively reduced ED2 staining but did not greatly affect HIS48 staining. Additional studies were performed to estimate the effect of retinol on noninflammatory processes. While total cytochrome P450 was not increased, the activity and concentration of CYP2E1 were both significantly elevated after a single dose of retinol. Hepatocytes isolated from 1-day retinol-treated rats were also more susceptible to CCl4 injury, a consequence that is most likely related to elevated CYP2E1 activity. These findings suggest that a single pretreatment with retinol may potentiate CCl4 hepatotoxicity by multiple mechanisms which involve increased biotransformation and inflammatory cell activities.
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PMID:The role of inflammatory cells and cytochrome P450 in the potentiation of CCl4-induced liver injury by a single dose of retinol. 897 75

From 1984 through 1992, staff at The Marine Mammal Center (TMMC, Sausalito, California, USA) examined 207 northern elephant seals (Mirounga angustirostris) with a condition of unknown etiology called northern elephant seal skin disease (NESSD). The skin lesions were characterized by patchy to extensive alopecia and hyperpigmentation, punctate or coalescing epidermal ulceration, and occasionally, massive skin necrosis. Microscopic lesions included ulcerative dermatitis with hyperkeratosis, squamous metaplasia and atrophy of sebaceous glands. All diseased seals were less than 2 years of age and suffered from emaciation, depression, and dehydration. Mortality from septicemia increased significantly with severity of skin ulceration. Compared to 14 apparently unaffected seals, diseased seals had depressed levels of circulating thyroxine, triiodothyronine, retinol, serum iron, albumin, calcium, and cholesterol. Levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transpeptidase, blood urea nitrogen, and uric acid were elevated. Morphometrically, diseased animals were approximately 15% smaller than normal seals of the same sage. Serum and blubber concentrations of 36 polychlorinated biphenyl congeners (sigma PCB) and dichloro-diphenyl-dichloroethylene (p,p'-DDE) were negatively correlated with body mass. Mean concentrations of sigma PCB and p,p'-DDE in serum in diseased seals were elevated as compared to apparently normal seals. Etiology of this syndrome remains unknown, but the possibility of PCB toxicosis cannot be ruled out.
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PMID:Clinical and pathological characterization of northern elephant seal skin disease. 924 88

In the mouse, retinol administration attenuates carbon tetrachloride (CCl4)-induced hepatic injury. We have investigated the role of cytochrome P4502E1 (CYP2E1) in this interaction. Male Swiss Webster mice were administered retinol (75 mg/kg/d) or vehicle for 3 days prior to CCl4 (30 microl/kg, ip). Hepatotoxicity produced by CCl4 was assessed by plasma alanine aminotransferase (ALT) activity and light microscopy (ALT activity of 1391+/-430 vs. 274+/-92 IU/L for vehicle + CCl4 and retinol + CCl4 treatments respectively, p < 0.05). Retinol's attenuation of liver injury was maintained when CCl4 was administered 48 h after the conclusion of the retinol pretreatment. Aniline hydroxylation activity, an indicator of CYP2E1 catalytic activity, determined on day 4 was 33.8% of untreated control in vehicle + CCl4 treatments while the retinol + CCl4 treatment group was 94.2% of untreated control. Additionally, CYP2E1 immunoreactive protein was 78% lower in vehicle + CCl4 vs. retinol + CCl4 treatment groups. Attenuation of potentiated hepatotoxicity was also observed when CYP2E1 was induced by acetone (ALT activity of 3119+/-1066 vs. 247+/-77 IU/L for vehicle and retinol treatments respectively, p < 0.05). In the mouse, retinol itself does not alter constitutive or inducible CYP2E1 expression. However, in combination with CCl4 retinol does reduce the amount of CCl4 bioactivated to its toxic metabolite. We conclude that retinol attenuates CCl4-induced hepatotoxicity by causing a decrease in CCl4 bioactivation but does not cause a decrease in CYP2E1 expression.
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PMID:Role of cytochrome P4502E1 in retinol's attenuation of carbon tetrachloride-induced hepatotoxicity in the Swiss Webster mouse. 1056 6

Retinol pretreatment (75 mg/kg/day, 4 days) potentiated paracetamol-induced hepatotoxicity in BALB/c mice (alanine aminotransferase (ALT) activity; 2510+/-602 vs 1155+/-282 IU/l; retinol+paracetamol vs corn oil+paracetamol, respectively, P<0.05); however, this potentiation did not occur in the kidney, indicating an organ-specific response. Retinol treatment alone was not toxic in either organ, as indicated by ALT activity, blood urea nitrogen and creatinine. The potentiation effect could be mediated by retinol's induction of CYP450 isoforms relevant to paracetamol metabolism or through depletion of glutathione. Therefore, these parameters were investigated in both organs. Following retinol treatment, renal CYP2E1 and hepatic CYP1A2 and CYP2E1 catalytic activities and polypeptide levels were unchanged. However, retinol significantly decreased both the catalytic activity (0.23+/-0.03 vs 0.53+/-0.06 nmol/mg/min; retinol vs untreated, respectively, P<0.05) and polypeptide levels (58+/-0.6% of control) of hepatic CYP3A. Inhibition of renal CYP3A did not occur as catalytic activity and polypeptide levels were unchanged from control. Following retinol treatment, total reduced glutathione levels, in both organs, were not significantly different from control. Therefore, the potentiation of paracetamol-induced hepatotoxicity is independent of CYP450 and glutathione.
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PMID:The effect of retinol on hepatic and renal drug-metabolising enzymes. 1125 46


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