Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome c release and mitochondrial permeability transition (MPT) play important roles in apoptosis. In this study, we found that selenium, an essential trace element, induced mitochondrial membrane potential (Delta psi(m)) loss, swelling, and cytochrome c release in isolated mitochondria. All of the above observations were blocked by cyclosporin A (CsA), which is a specific inhibitor to permeability transition pore (PTP), indicating selenite-induced mitochondrial changes were mediated through the opening of PTP. In physiological concentration, selenite could induce mitochondria at low-conductance PTP 'open' probability, which is correlated to regulate the physiological function, whereas in toxic concentration, induce mitochondria at high-conductance PTP 'open' probability and rapidly undergo a process of osmotic swelling following diffusion toward matrix as for inducer (Ca(2+)/P(i)). Selenite also induced other mitochondrial marker enzymes including monoamine oxidase (MAO) and mitochondria aspartate aminotransferase (mAST). Oligomycin inhibited the selenite-induced cytochrome c release and Delta psi(m) loss, showing that F(0)F(1)-ATPase was important in selenite or Ca(2+)/P(i)-induced MPT.
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PMID:Mitochondrial permeability transition and cytochrome c release induced by selenite. 1200 54

The occupational importance of tellurium and selenium is growing rapidly, but the biochemistry of exposure is poorly understood. Here we report the potential toxic effects of diphenyl diselenide (PhSe)(2), diphenyl ditelluride (PhTe)(2) and Ebselen in rats and mice. The results suggest that (PhTe)(2) is more toxic in rats than mice. (PhSe)(2), (PhTe)(2) and Ebselen are more toxic by intraperitoneal (i.p.) than subcutaneous (s.c.) route. Calculated LD(50) for (PhTe)(2), i.p., was 0.65 micromol/kg in rats and 150 micromol/kg in mice, and LD(50), s.c., was 0.9 micromol/kg in rats and >500 micromol/kg in mice. Calculated LD(50) for Ebselen, i.p., was 400 micromol/kg in rats and 340 micromol/kg in mice and LD(50), s.c., was >500 micromol/kg in both mice and rats. (PhTe)(2) at small doses increased 2-fold serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in rats. LD(50) for all organochalcogens administrated in mice inhibited blood delta-ALA-D activity. The present study provides evidence for liver and renal toxicity of (PhTe)(2).
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PMID:Potential renal and hepatic toxicity of diphenyl diselenide, diphenyl ditelluride and Ebselen for rats and mice. 1269 75

Halothane, commonly used for anesthetizing humans and animals, is one of the most important volatile anesthetics and may cause the formation of free radicals during its biotransformation. Free radicals may lead to degeneration of liver cells. Vitamin E and glutathione peroxidase (GSH-Px) containing selenium are two natural antioxidants, and these may protect the cellular lipid and lipoproteins against oxidative damage caused by free radicals. Therefore, the purposes of the present study were to investigate the probable protective effects of intraperitoneally administered Se and vitamin E on liver enzymes and to determine some other hematological parameters in the halothane anesthesia of rats. All rats were randomly divided into five groups. The first group was used as a control, and physiological saline (0.9%) was intraperitoneally injected into these animals as a placebo. The second group was used as an anesthesia control group and was only anesthetized with halothane for two hours. The third group received intraperitoneally administered Se (Na2SeO3, 0.3 mg/200 g body weight), the fourth group vitamin E (dl-alpha-tocopheryl acetate, 100 mg/kg body weight), and the fifth group a Se plus vitamin E combination (Na2SeO3, 0.3 mg/200 g body weight + dl-alpha-tocopheryl acetate, 100 mg/kg body weight). The activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, triglycerides, erythrocyte counts, the packet-cell volume, hemoglobin concentrations and neutrophyle rates significantly increased (p < 0.05 to p < 0.01) after halothane anesthesia and returned to near control levels after Se, vitamin E and Se plus vitamin E injections. The values of cholesterol, total protein, white blood cell counts and lymphocyte rates significantly decreased (p < 0.05 to p < 0.01) in the anesthesia control group. However, the levels of albumin, total bilirubin, creatinine, the mean corpuscular volume, the mean corpuscular hemoglobin, and the mean corpuscular hemoglobin concentration were not statistically influenced. In conclusion, we have determined that halothane anesthesia affected some liver enzymes and some other biochemical and hematological parameters. Se, vitamin E and their combination may prevent the increase of liver enzymes after halothane anesthesia. Based upon these results, Se and vitamin E may play an important role in the indication of hepatic cellular injury produced by halothane.
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PMID:Effects of intraperitoneally injected selenium and vitamin E in rats anesthetized with halothane. 1275 99

In this study, the effect of a combination of vitamin C (ascorbic acid), vitamin E (dl-alpha-tocopherol acetate), and selenium (sodium selenate) on ethanol-induced liver damage in rats was investigated, morphologically and biochemically. The ethanol-induced injury was produced by the administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) (ViCESe) for 3 d 1 h prior to the administration of absolute ethanol. In the liver of the animals given ethanol, the degenerative changes such as extreme hyperemia, vacuolization in cells of portal areas, a dilation in sinusoids, mononuclear cell infiltration, a swelling in cisternae of granular endoplasmic reticulum and in mitochondrial cristae, an increase in smooth endoplasmic reticulum, many lipid vacuoles were observed both light and electron microscopically. A similar structure was usually distinguished when compared with control animals, in rats given ethanol + ViCESe. In this group, the findings indicating cellular damage were either not observed at all or were decreased. In the group administered ethanol, a reduction of the blood glutathione (GSH) level and increases in serum values of alanine aminotranserase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) activities were observed, whereas in the control group, the reverse was found to occur. On the other hand, in the group in which ethanol + ViCESe was administered, it was observed that the blood GSH value and serum ALP and ALT activities increased and serum AST, LDH, and GGT activities decreased. As a result, the present study indicates that ViCESe because of their antioxidant activity against ethanol damage have a protective effect on the liver.
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PMID:Protective effects of ascorbic acid, dl-alpha-tocopherol acetate, and sodium selenate on ethanol-induced liver damage of rats. 1498 25

The most important antioxidant aspect of selenium is its function in the active site of selenoenzyme glutathione peroxidase. Glutathione peroxidase not only allows the removal of the toxic radicals but also permits the regeneration of lipid molecules through reacylation in the cellular membrane. Thus, GSHPx may prevent the harmful effects of free radicals and may reduce the formation of the reactive metabolites of carbon tetrachloride. Carbon tetrachloride is a hepatotoxic agent which generates haloalkane radicals during its biotransformation in the liver and is widely used to make the experimental model of hepatic damage. Therefore, the aim of the present study is to investigate the possible protective role of selenium on the experimental liver cirrhosis and some enzyme activities in blood plasma from rats. While the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly increased (p < 0.05, p < 0.05 and p < 0.01, respectively), gamma-glutamyle transferase (GGT) activity was not statistically affected (p < 0.05) with carbon tetrachloride-injection. The levels of AST, ALT and GGT in carbon tetrachloride-group decreased to nearly the enzyme values in control-group after the selenium-injection but the ALP was increased (p<0.01). On the other hand, it was noticed that selenium significantly decreased the hepatic injury. In conclusion, our results showed that carbon tetrachloride caused an increase in the activities of liver enzymes in plasma and selenium application decreased the hepatic injury. Plasma levels of the liver enzymes were decreased after selenium-injections. Based upon these results, selenium may play an important role in the preventive indication of hepatic cellular injury inducted by carbon tetrachloride.
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PMID:Effects of selenium on histopathological and enzymatic changes in experimental liver injury of rats. 1558 Dec 76

We previously reported that, as compared with selenite, nano red elemental selenium (Nano-Se) had lower acute toxicity in mice and similar bioavailability in terms of up-regulating seleno-enzymes. The short-term toxicity of both selenite and Nano-Se in mice was further compared in this study. At an oral dose of 6 mg/kg bw per day administered for consecutive 12 days, selenite and Nano-Se completely and partially suppressed mice growth respectively. Abnormal liver function was more pronounced with selenite treatment than Nano-Se as indicated by the increase of both alanine aminotransferase and aspartate aminotransferase in serum. Selenite inhibited liver catalase and superoxide dismutase activities, whereas, Nano-Se did not affect these two antioxidant enzymes. Selenite increased the malondialdehyde content of liver, but Nano-Se decreased it. Both Se forms had similar effects on depletion of reduced glutathione and up-regulated glutathione peroxidase. Nano-Se was more potent than selenite in the induction of glutathione S-transferase. At oral doses of 2 or 4 mg/kg bw per day for consecutive 15 days, selenite was more active than Nano-Se in supressing growth, deleting reduced glutathione, and inhibiting superoxide dismutase activities. Taken together, these results indicate that over a short-term, a high-dose of selenite caused more pronounced oxidative stress, greater liver injury, and prominent retardation of growth as compared to Nano-Se.
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PMID:Comparison of short-term toxicity between Nano-Se and selenite in mice. 1562 May 74

The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. In the present investigation subchronic deleterious effects of cadmium-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g) received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A number of toxicological parameters in blood, liver, kidney, spleen and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation and ascorbic acid content, the parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were also determined. The results demonstrated that cadmium caused inhibition of delta-ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy was effective in restoring enzyme activity in all tissues. A reduction in ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium-treated mice and (PhSe)2 was only effective in improving this reduction in kidney. An increase of lipid peroxidation induced by cadmium was noted in liver (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99-times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was effective in restoring AST activity at control level. (PhSe)2 did not present toxic effects when plasma parameters were evaluated. The results suggest that the administration of an antioxidant (PhSe)2, during cadmium intoxication may provide beneficial effects by reducing oxidative stress in tissues.
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PMID:Diphenyl diselenide reverses cadmium-induced oxidative damage on mice tissues. 1573 37

This study was designed to determine the toxic effects of nickel sulfate on the biochemical and elemental profile of liver in protein deficient rats. Nickel sulfate in the dose of 800mg/l in drinking water was administrated to Sprauge Dawley (S.D) normal control as well as protein deficient rats for a total duration of eight weeks. The effects of nickel treatment and protein deficiency when given separately and in combination were studied on rat liver marker enzymes like Alkaline phosphatase (ALP),Glutamate oxaloacetate transaminase (GOT), Glutamate pyruvate transaminase (GPT) and also on the status of essential elements in rat liver. Protein deficient, Ni treated as well as combined protein deficient and nickel treated rats showed significant reductions in the body weight and hepatic protein contents as compared to normal control rats. Hepatic alkaline phosphatase activity and alanine aminotransferase showed a significant elevation in rats subjected to protein deficiency, nickel treatment and combined protein deficiency and nickel treatment. As regards to hepatic levels of aspartate aminotransferase a significant elevation was observed in protein deficient and nickel treated protein deficient animals. Nickel administration to normal and protein deficient rats has resulted in a significant increase in concentrations of nickel, phosphorus and sulfur in liver tissue. The concentration of zinc and copper in liver tissue decreased significantly in protein deficient, nickel treated and nickel treated protein deficient animals. Tissue iron concentrations were found to be decreased in protein deficient animals, but the concentrations of iron got elevated significantly in nickel treated and nickel treated protein deficient animals. It has been observed that selenium got decreased significantly in protein deficient, nickel treated and nickel treated protein deficient animals when compared to normal animals. The elevation of selenium in nickel treated protein deficient animals was also significantly higher when compared to protein deficient animals.
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PMID:Ineffectiveness of nickel in augmenting the hepatotoxicity in protein deficient rats. 1633 21

We investigated the effect of choice feeding two diets with different selenium (Se) content to young and old moderately Se-deficient laying hens on serum Se (SSe), glutathione peroxidase (GPX), vitamin E, creatine kinase (CK), aspartate aminotransferase (ASAT), thyroxine (T4) and triiodothyronine (T3). Each of two consecutive study parts (I and II) with the same hens and treatments began with a 6-week baseline period (Medium-Se diet), followed by a 9-week depletion period (Low-Se or Medium-Se diet), followed by a 6-week choice period with two different diets offered simultaneously (Medium-Se/Low-Se, Medium-Se/High-Se, or Low-Se/High-Se). During both depletion periods, SSe and GPX gradually decreased, whereas T4 gradually increased in hens fed Low-Se confirming gradual Se-depletion. T3 decreased transiently in young hens only. As reported earlier, Se-deficient hens preferred High-Se over Low-Se diet during the first 3 weeks of choice feeding in part I, not however in part II. This preference resulted in higher SSe in these hens. GPX activity did not reflect feed preference, probably because Se-intake exceeded Se-requirement for maximal GPX activity. In Part II, hens depleted with Low-Se diet had higher SSe when previously offered High-Se diet in either combination, than when offered Low-Se/Medium-Se, presumably due to Se-stores built during choice feeding in part I, which possibly prevented development of Se-deficiency in part II. In addition, in older hens, Se depletion proceeded faster, whereas Se-repletion by choice feeding was slower than in young hens, indicating the increase in Se requirement with advancing age. Vitamin E, ASAT and CK remained largely unchanged by the treatments.
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PMID:Effects of selenium depletion and selenium repletion by choice feeding on selenium status of young and old laying hens. 1637 89

The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. The present study was conducted to evaluate the potential toxicity of long time oral exposure to diphenyl diselenide (PhSe)2 in rabbits. Male adult New Zealand rabbits were divided into four groups, group I served as control; groups II, III and IV received 0.3, 3.0 and 30 ppm of (PhSe)2 pulverized in the chow for 8 months. A number of parameters were examined in blood as indicators of toxicity, including delta-aminolevulinate dehydratase (delta-ALA-D), catalase, glutathione peroxidase (GPx), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine, TBARS, non-protein-SH, ascorbic acid and selenium. The results demonstrated that 6 and 8 months of 30 ppm (PhSe)2 intake caused a significant increase in blood delta-ALA-D activity. Erythrocyte non-protein thiol levels were significantly increased after 2 months of 30 ppm (PhSe)2 intake and then return to control levels after prolonged periods of intake. Ingestion of 3.0 ppm of (PhSe)2 for 8 months significantly increased catalase activity in erythrocytes. Conversely, no alterations in GPx, ALT, AST, TBARS and selenium levels were observed in rabbit serum, conversely, selenium levels in peri-renal adipose tissue were significantly increased after 8 months of 30 ppm (PhSe)2 intake, indicating its great lipophylicity. The present results suggest that diphenyl diselenide was not hepato- or renotoxic for rabbits, but caused some biochemical alterations that can be related to some pro-oxidant activity of the compound (particularly the reduction in Vitamin C).
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PMID:Changes in biochemical parameters in rabbits blood after oral exposure to diphenyl diselenide for long periods. 1673 89


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