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)

We previously reported that Wistar-Imamichi (WI) rats have a strong resistance to cadmium (Cd)-induced lethality compared to other strains such as Fischer 344 (Fischer) rats. The present study was designed to establish biochemical and histological differences in Cd toxicity in WI and Fischer rats, and to clarify the mechanistic basis of these strain differences. A single Cd (4.5 mg/kg, s.c.) treatment caused a significant increase in serum alanine aminotransferase activity, indicative of hepatotoxicity, in Fischer rats, but did not in WI rats. This difference in hepatotoxic response to Cd was supported by pathological analysis. After treatment with Cd at doses of 3.0, 3.5 and 4.5 mg/kg, the hepatic and renal accumulation of Cd was significantly lower in the WI rats than in the Fischer rats, indicating a kinetic mechanism for the observed strain differences in Cd toxicity. Thus, the remarkable resistance to Cd-induced hepatotoxicity in WI rats is associated, at least in part, with a lower tissue accumulation of the metal. Hepatic and renal zinc (Zn) contents after administration were similarly lower in WI than in Fischer rats. When Zn was administered in combination with Cd to Fischer rats, it decreased Cd contents in the liver and kidney, and exhibited a significant protective effect against the toxicity of Cd. We propose the possibility that Zn transporter plays an important role in the strain difference of Cd toxicity in WI and Fischer rats.
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PMID:Strain differences of cadmium-induced hepatotoxicity in Wistar-Imamichi and Fischer 344 rats: involvement of cadmium accumulation. 1536 94

This study was planned to determine the protective role of zinc, if any, in attenuating the toxicity induced by nickel sulfate in rat liver. Female Sprague Dawley (SD) rats received either nickel alone in the dose of 800 mg/l in drinking water, zinc alone in the dose of 227 mg/l in drinking water, and nickel plus zinc or drinking water alone for a total duration of eight weeks. The effects of different treatments were studied on various parameters in rat liver which include antioxidant enzymes, levels of nickel and zinc and histoarchitecture at the light microscopic level. Further, the activities of hepatic marker enzymes AST and ALT were also studied in rat serum. Nickel treatment to the normal control animals, resulted in a significant increase in lipid peroxidation and enzyme activities of catalase and glutathione-S-transferase. On the contrary, nickel treatment to normal rats caused a significant inhibition in the levels of reduced glutathione. Superoxide dismutase activity was found to be decreased which however was not significant. Interestingly, when Zn was supplemented to nickel treated rats, the activities of catalase, and glutathione-S-transferase and the levels of GSH and lipid peroxidation came back to within normal limits. Activities of serum AST and ALT were increased significantly following nickel treatment to normal rats. Simultaneous zinc administration to nickel treated rats tended to restore the altered levels of AST and ALT. Normal control and zinc treated animals revealed normal histology of liver. On the other hand, nickel treated animals showed alterations in normal hepatic histoarchitecture which comprise of vacuolization of the hepatocytes and dilatation of sinusoids as well as increase in the number of bi-nucleated cells. Administration of zinc to nickel treated rats resulted in marked improvement in the structure of hepatocytes, thus emphasizing the protective potential of zinc in restoring the altered hepatic histoarchitecture. The nickel administration to normal rats indicated increased concentrations of nickel and decreased concentrations of zinc. However, zinc effectively brought the altered levels of nickel and zinc to within normal range. The study concludes that zinc has the potential in alleviating the toxic effects of nickel in rat liver because of its property to induce metallothionein (S-rich protein) as a free radical scavenger, or its indirect action in reducing the levels of oxygen reactive species.
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PMID:Protective role of zinc in nickel induced hepatotoxicity in rats. 1553 90

This study was designed to determine the protective effects of zinc on the hepatotoxicity induced by nickel in rats. Female Sprague-Dawley (SD) rats received either nickel sulfate alone in the dose of 800 mg/L nickel in drinking water, zinc sulfate alone in the dose of 227 mg/L zinc in drinking water, and nickel plus zinc or drinking water alone for a total duration of 8 wk. The effects of different treatments were studied on activities of rat liver marker enzymes like alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferases (AST) and on the status of essential elements in rat liver. The study revealed a significant increase in the activities of enzymes ALP and ALT in rats subjected to nickel treatment. Interestingly, zinc supplementation to rats treated with nickel brought back the raised activities of these enzymes to within normal limits. Further, the levels of elements in liver that include zinc, copper, selenium, and potassium were found to be significantly suppressed following nickel treatment, whereas the levels of iron and sulfur were elevated. However, zinc treatment alone did not cause any appreciable change in the concentration of these elements. To the contrary, when zinc was given to nickel-treated rats, the concentrations of zinc, copper, potassium, and phosphorus were not significantly different from that of normal controls, whereas the levels of iron, selenium, and sulfur were improved in comparison to nickel-treated rats but were not within the normal limits. The present study concludes that zinc has the ability to maintain the levels of hepatic elements and has bearing in regulating the liver functions by maintaining the activities of marker enzymes in conditions of nickel toxicity.
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PMID:Role of zinc in regulating the levels of hepatic elements following nickel toxicity in rats. 1562 36

Concomitant oral supplementation of Aloe vera, (1, 2 or 5% w[sol ]v in drinking water) during arsenic exposure (0.2 mg[sol ]kg, intraperitoneally, once daily for 3 weeks) was investigated in rats for its protective value. Animals exposed to arsenic (III) showed a significant inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity, a marginal decrease in glutathione (GSH) and an increase in zinc protoporphyrin (ZPP) level in blood. White blood corpuscles (WBC) level decreased while most of the other clinical blood parameters like red blood cells count, haemoglobin, MCV, MCH, MCHC ratio and platelet number, etc. remained unaltered on arsenic exposure. Hepatic reduced GSH, oxidized glutathione (GSSG) level remained unaltered, thiobarbituric acid reactive substance (TBARS) level increased significantly while the activity of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and catalase decreased on arsenic exposure. Renal GSH contents decreased while superoxide dismutase (SOD) activity decreased significantly on arsenic exposure. Concomitant administration of Aloe vera had remarkable protective action on inhibited blood ALAD activity and restored blood GSH level while most of the other blood biochemical parameters remained unchanged on Aloe vera supplementation. Interestingly, most of hepatic biochemical variables indicative of oxidative stress showed protection; no effect of Aloe vera on blood and liver arsenic concentration was noted. Also, no effect of Aloe vera on most of the altered renal biochemical parameters were noticed. The results thus lead us to conclude that simultaneous supplementation of Aloe vera protects against arsenic induced oxidative stress but does not influence the arsenic concentration in these organs.
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PMID:Protective value of Aloe vera against some toxic effects of arsenic in rats. 1579 4

Wilson's disease (WD) is an inherited disorder of copper metabolism characterized by a failure of the liver to excrete copper, leading to its accumulation in the liver, brain, cornea, and kidney, with resulting chronic degenerative changes. It is generally accepted that "presymptomatic" patients--in whom WD is diagnosed in childhood and who are defined as those who, although still asymptomatic, do have liver disease, as indicated by increased serum concentrations of transaminases--should be treated prophylactically. Here we report our results in 22 children treated with continuous oral zinc therapy for 10 years. Zinc sulfate was administered at a dosage of 25 mg elemental zinc twice a day until the age of 6 years, 25 mg three times a day between the ages of 7 and 16 years or until the child attained a body weight of 125 lb, and 50 mg three times a day thereafter. Five years after the start of zinc treatment, we noted highly significant decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urinary copper excretion, but white blood cell counts did not vary significantly. Six of 22 patients continued to demonstrate greater-than-normal ALT concentrations and only 1 patient demonstrated an ALT concentration more than 1.5 times the upper normal limit. Further decreases in ALT, AST, and urinary copper excretion were observed at the end of the 10-year follow-up, but these decreases were not statistically significant. Only 1 patient continued to demonstrate abnormal ALT levels. Again, white blood cells showed no significant variations. All histologic scores (steatosis, inflammation, and fibrosis) were significantly decreased after treatment. Hepatic copper content was also significantly decreased, although it remained higher than normal in all patients. The removal of toxic copper was confirmed by disappearance of Kayser-Fleischer rings in 3 patients. Zinc did not have adverse effects on growth. The efficacy of zinc in WD in presymptomatic pediatric patients has been established in previous studies, and our study adds considerably to the earlier findings because it includes a large number of very young children, as many as 11 younger than 6 years and 20 younger than 10. The excellent clinical results in all patients, coupled with the improvement in hepatic histologic findings in the vast majority, indicate convincingly that zinc treatment can control the disease effectively and safely, preventing its progression over the course of 10 years. Histologic findings reportedly improved in 3 patients treated in an earlier study, but our data are numerically much more relevant. Notably, histologic study of the liver revealed that copper concentration was reduced by treatment, suggesting that oral zinc was able not only to prevent further accumulation of copper but also to promote, at least in part, the depletion of its stores. The lack of adverse effects of zinc on growth suggests that our patients received enough anticopper therapy to prevent damage resulting from copper toxicity but an adequate amount of copper for proper growth and development. In conclusion, our findings indicate that zinc is the treatment of choice in presymptomatic pediatric patients with WD.
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PMID:Treatment of Wilson's disease with zinc from the time of diagnosis in pediatric patients: a single-hospital, 10-year follow-up study. 1587 5

Since 1975, our experience in the treatment of biliary atresia with Kasai's technique has improved little by little, achieving 65% favourable outcome in the last five years. We define "good results" as the complete restoration of biliary flow and normalization of bilirrubin levels. The long-term evolution of these good results can be diverse. The objective of the present work is to analyze the outcome of patients in our series in whom a favourable initial response was achieved, as well as evaluating their present situation and future perspectives. The authors present a total of 17 patients operated by Kasai's technique since 1985, that constitutes the group with good results in our series. The controls were based on general analysis, liver function and periodic ultrasound explorations. All received a standardized medical treatment consisting of vitamin supplements (A, D3, E, K) minerals (zinc, calcium, phosphate, iron) ursodexoxicolic acid, luminal,as well as close control of calorie intake. In two patients the levels of bilirrubine were progressively increased with time, stabilizing at between 5/6 mgs/100 ml, with progressive hepatic hardening, appearance of splenomegalia, indirect signs of portal hypertension and a slight deterioration of hepatic function. One received a transplant at age 12 with Quick levels below 50%. The other, aged 16, continues with an acceptable hepatic function and good quality of life under recommendation of transplant. Eleven patients with ages ranging from fourteen months to seventeen years presented slight and firm hepatomegalia, moderate portal hypertension, GOT 71 +/- 8 mg/100 ml, GPT 97 +/- 11 mg/100 ml and normal bilirrubine levels. From this group, 3 patients, all under five years of age, experienced bleeding from esophageal varices which were controlled by sclerosis and medical treatment (propanolol and isosorbide dinitrate). Recently, one three year-old patient developed a hepatocarcinoma of rapid, mortal evolution. Since then, the determination of alfa-feto protein in follow-up controls has been introduced. Four other patients of 5, 6, 14, 16, years of age are completely assymptomatic with an excellent clinical evolution. In our experience,the patients that overcome the third year after surgery without serious complications seem destined to reach puberty with a good quality of life. However, some cases show signs of hepatic fibrosis and portal hypertension, 77% in our series. Only 23% of patients with a favorable initial evolution appear to present a complete normalization of their hepatic lesion in the long term.
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PMID:[Biliary atresias operated with favourable results: predictable outcome]. 1590 Nov 4

A survey was conducted in 10 districts of northern India. Significant deficiency of zinc was observed in soil, fodders and (cattle) serum samples. The animals showed typical signs of zinc deficiency, namely stiff gait, swelling of hocks and knees, subcutaneous fluid accumulation, rough coat, etc. of variable intensity. A clustered model therapeutic trial was conducted and zinc-deficient cattle were divided into three groups. Group A was provided with mineral mixture containing zinc sulphate. Group B was given mineral mixture without zinc sulphate and group C was given no mineral mixture. Significant improvement (p < 0.01) was observed in the haemoglobin (Hb), total white blood cells (WBC) and total erythrocyte count (TEC) levels at the 7th day of treatment in the animals of group A. Significant improvement in enzyme serum alkaline phosphatase (SAP) was observed in group A animals at the 7th day, while improvement in asparatate aminotransferase (AST), alanine aminotransferase (ALT) and ceruloplasmin (Cp) was observed after 21 days of treatment. Regarding hormones, significant improvement was observed in thyroxine (T3) and triiodothyronine (T4), oestrogen and progesterone in group A animals within 14 days of treatment. The values of vitamin A showed a highly significant (p < 0.01) improvement within 7 days of treatment in group A animals and that of vitamin E on the 21 st day of treatment. The milk yield of lactating cattle and body weight of growing calves in group A showed highly significant (p < 0.01) increases at about 14 and 30 days, respectively. It is concluded that zinc sulphate supplementation is highly effective in alleviating zinc deficiency and improving various biochemical and production parameters in cattle. The clustered model treatment provides a better indicator of the most limiting element under field conditions where simultaneous deficiency of various minerals is prevalent.
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PMID:Therapeutic efficacy of zinc sulphate used in clustered model treatment in alleviating zinc deficiency in cattle and its effect on hormones, vitamins and production parameters. 1614 8

The purpose of this study is to evaluate the acute toxicity of oral exposure to nanoscale zinc powder in mice. The healthy adult male and female mice were gastro-intestinally administered at a dose of 5 g/kg body weight with two size particles, nanoscale zinc (N-Zn) and microscale zinc (M-Zn) powder, while one group mice treated with sodium carboxy methyl cellulose was used as the control. The symptoms and mortality after zinc powder treatment were recorded. The effects of particles on the blood-element, the serum biochemical level and the blood coagulation were studied after 2 weeks of administration. The organs were collected for histopathological examination. The N-Zn treated mice showed more severe symptoms of lethargy, vomiting and diarrhea in the beginning days than the M-Zn mice. Deaths of two mice occurred in the N-Zn group after the first week of treatment. The mortalities were confirmed by intestinal obstruction of the nanoscale zinc aggregation. The biochemical liver function tests of serum showed significantly elevated ALT, AST, ALP, and LDH in the M-Zn mice and ALT, ALP, and LDH in the N-Zn mice compared with the controls (P<0.05), which indicated that the liver damage was probably induced by both micro- and nano-scale zinc powders. The clinical changes were observed in the two treated group mice as well. The levels of the above enzymes were generally higher in the M-Zn mice than in the N-Zn mice, which implied that M-Zn powder could induce more severe liver damage than N-Zn. The biochemical renal function tests of serum BUN and CR in the M-Zn mice markedly increased either compared with the N-Zn mice or with the controls (P<0.05), but no significant difference was found between the N-Zn and the control mice. However, severe renal lesions were found by the renal histopathological examination in the N-Zn exposed mice. Therefore, we concluded that severe renal damage could occur in the N-Zn treated mice, though no significant change of blood biochemical levels occurred. Blood-element test showed that in the N-Zn mice, PLT and RDW-CV significantly increased, and HGB and HCT significantly decreased compared to the controls, which indicated that N-Zn powder could cause severe anemia. Besides the pathological lesions in the liver, renal, and heart tissue, only slight stomach and intestinal inflammation was found in all the zinc treated mice, without significant pathological changes in other organs.
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PMID:Acute toxicity of nano- and micro-scale zinc powder in healthy adult mice. 1616 31

Metallothionein (MT) is a small sulfydryl-rich protein that binds to and is inducible by heavy metals such as mercury, cadmium, zinc, and copper. However, little is known about the induction of MT by trivalent metals except for bismuth. In this study, we examined the induction of MT synthesis by cerium, a trivalent lanthanoid metal. Administration of cerium chloride (CeCl3) to mice resulted in accumulation of cerium and induction of MT in the liver in a dose-dependent manner. Distribution profiles of metals in the soluble fraction of the liver of CeCl3-treated mice analyzed by high performance liquid chromatography/inductively coupled argon plasma-mass spectrometry (HPLC/ICP-MS) demonstrated that the metal bound to MT-I and MT-II was zinc, but not cerium. Administration of CeCl3 caused increases in the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the levels of serum amyloid A (SAA), an acute phase protein. Among inflammatory cytokines examined, interleukin 6 (IL-6) exhibited a marked increase in the serum at 3 h after the CeCl3 administration. In order to evaluate the involvement of IL-6 in the induction of MT by cerium, we examined MT induction by CeCl3 in IL-6 null mice. Both the induction of hepatic MT and the increases in SAA levels were markedly suppressed in IL-6 null mice. These results suggest that IL-6 plays an important role in the induction of hepatic MT by cerium.
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PMID:Induction of hepatic metallothionein by trivalent cerium: role of interleukin 6. 1620 35

The present study was undertaken in order to investigate the effect of subchronic exposure of rats to static magnetic field (SMF) and/or zinc treatment on the selected hematological and biochemical parameters. Metallothioneins (MT) and zinc content in kidney and liver were studied. The exposure of rats to SMF for 1h/day during 30 consecutive days induced an increase in hemoglobin concentration, white blood cell count (WBC), red blood cell count (RBC) and platelet number. By contrast, hematocrit remained unchanged. The same treatment also increased the serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. However, the creatinine and urea concentrations were similar to those of controls. On the other hand, renal and hepatic zinc levels were not altered in SMF treated-rats. SMF exposure induced MT synthesis in the liver and kidney. Zinc administration (40 mg/l for 30 consecutive days, in drinking water) had no effect on hematological and biochemical parameters. However, hepatic and renal zinc content and MT levels were increased. Zinc prevented the increase in serum transaminase activities, and WBC and platelet counts induced by SMF. However, the elevation of the LDH, hemoglobin and RBC levels induced by SMF exposure was not suppressed. MT concentrations in both tissues were potentiated by zinc administration in SMF-exposed rats. It is suggested that zinc supplementation could prevent toxic effects of SMF probably by its anti-oxidant properties.
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PMID:Zinc prevents hematological and biochemical alterations induced by static magnetic field in rats. 1622 45


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