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)

In a 106-wk toxicity and carcinogenicity study, groups of 60 male and 60 female weanling Wistar rats were fed 0, 0.5, or 50 mg bis(tri-n-butyltin)oxide (TBTO)/kg diet. In males, feed consumption was increased in all treated groups and increased water consumption occurred at 5 and 50 mg/kg. During the second year, body weight decreased in the 50-mg/kg males, while the females in that group showed no weight gain. Excess mortality was confined to the 50-mg/kg group towards the end of the study. Haematological changes, comprising anaemia, lymphocytopenia and thrombocytosis were noted mainly at the high-dose level. Also, signs of decreased kidney function and increased plasma enzyme activities (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) were noted. No effects on serum hormone concentrations (thyrotropin, follicle stimulating hormone, luteinizing hormone or insulin) were observed, except for a decrease in the free thyroxin:thyroxin ratio in both sexes at the high-dose level. Higher serum IgM and IgA levels were present at 50 mg/kg, while, in females, IgG was decreased. At 50 mg/kg, the ovaries, adrenals, spleen (females), heart (males), pituitary, liver and kidneys were increased in weight, but the thyroid weight was decreased in females. The total tin concentrations in liver and kidneys showed a dose relationship and, in general, the concentrations were similar after 1 and 2 yr. Non-neoplastic histological alterations after 1 yr consisted of a decrease in the cell height of the thyroid follicles in all dose groups, with a reduced number of psammoma bodies at 50 mg/kg, a decrease in splenic iron content at 5 (females only) and 50 mg/kg, and a slight bile-duct activation. After 2 yr, only the thyroid changes were still present. In addition, at 2 yr, vacuolation and pigmentation of the proximal tubular epithelium and nephrosis were enhanced at 50 mg/kg. The incidence of benign tumours of the pituitary was significantly elevated and enhanced at 0.5 and 50 mg/kg. At 50 mg/kg increases in pheochromocytomas in the adrenal medulla and in parathyroid adenomas (males) were noted, while adrenal cortical tumours were decreased (males). There was a low, non-dose-related incidence of pancreatic carcinoma. Other tumour rates were in line with control data. It is concluded that lifetime feeding of 50 mg TBTO/kg diet induces toxicity in various organ systems. An increase in some common tumours was found at the high dose, probably due to hormonal or immunological changes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic toxicity and carcinogenicity of bis(tri-n-butyltin)oxide (TBTO) in the rat. 234 92

1,2-Dichloroethane produces kidney damage, but the mechanism is unclear. Cysteine conjugates, which could arise from S-(2-chloroethyl)glutathione or S-(2-chloroethyl)cysteine have been identified. In this study, rats given S-(2-chloroethyl)-DL-cysteine (100 mg/kg i.p.) showed significant increases in blood urea nitrogen and urine glucose concentrations. Histopathological examination of kidneys, 36 hr after treatment showed acute proximal tubular nephrosis and punctuate glomerular necrosis. No hepatic lesions were seen and serum glutamate-pyruvate transaminase activities were only elevated slightly. The extent of S-(2-chloroethyl)-DL-cysteine renal toxicity was dose- and time-dependent. Equimolar doses of analogs of S-(2-chloroethyl)-DL-cysteine, S-ethyl-L-cysteine, S-(2-hydroxyethyl)-N-acetyl-DL-cysteine, S-(2-hydroxyethyl)-DL-cysteine, or S-(3-chloropropyl)-DL-cysteine, failed to produce nephrotoxicity; rats given L-cysteine (100 mg/kg i.p.), S-ethyl-L-cysteine (100 mg/kg i.p.) or probenecid (60 mg/kg i.p.) 30 min before receiving S-(2-chloroethyl)-DL-cysteine had significant reductions of the S-(2-chloroethyl)-DL-cysteine-induced blood urea nitrogen and urine glucose elevations. These results show that S-(2-chloroethyl)-DL-cysteine is a potent, selective nephrotoxin that may be responsible for the renal damage associated with 1,2-dichloroethane. The formation of an episulfonium ion plays an important role in S-(2-chloroethyl)-DL-cysteine-induced nephrotoxicity. The protection against renal damage provided by S-ethyl-L-cysteine or probenecid may involve competition with S-(2-chloroethyl)-DL-cysteine for cellular or transport binding sites.
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PMID:Structure-nephrotoxicity relationships of S-(2-chloroethyl)-DL-cysteine and analogs: role for an episulfonium ion. 399 33

Adriamycin, an anticancer drug, caused dramatic increases in the serum lipid levels of rats fed a high-cholesterol diet. Male Lewis inbred rats were fed a basal or 1.5% cholesterol diet containing 0.5% cholic acid for 8 weeks. The rats were injected with adriamycin in doses of 1.5 mg/kg body weight, twice a week, and 6.0 mg/kg body weight, every other week. The serum lipid peroxide level gradually rose in adriamycin-treated rats, reaching a four-fold level at the end of the experiment. Cholesterol feeding, however, had a lowering effect on the lipid peroxide level. Adriamycin treatment or cholesterol feeding moderately elevated serum lipid levels, but their combination exerted a synergistic effect. In rats injected with a large dose of adriamycin and fed a high-cholesterol diet, the serum cholesterol, triglyceride and phospholipid levels strikingly increased by approx. 2000, 1500 and 1300 mg/100 ml, respectively. However, the ester ratio of cholesterol remained almost constant. Furthermore, serum GOT, GPT and ALP activities were only slightly different from the control values. Adriamycin treatment produced severe hypoalbuminemia. Ascites was also observed in rats given a large dose of adriamycin. The present findings indicate that the hyperlipidemia we observed may basically result from adriamycin-induced nephrosis and can be markedly enhanced when rats are fed a high-cholesterol diet. In spite of remarkably high levels of serum lipids and lipid peroxides, the aortic cholesterol level increased only slightly.
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PMID:Hyperlipidemic effects of adriamycin in rats. 409 81

Three calves received 10 g Riedeliella graciflora dry leaves/kg body weight by gavage. Blood samples were taken immediately before plant administration and at 2, 4, 6, 12 and 24 hours later; serum ALT, AST, AP, TB, urea and creatinine were determined. After R graciflora administration, the calves had anorexia, profound depression and recumbency prior to death. Creatinine levels increased markedly until death. Severe tubular nephrosis was consistently observed.
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PMID:The acute toxicity of Riedeliella graciflora in calves. 859 33

Aminoglycoside antibiotics are indispensable for treatment of serious bacterial infections, and despite careful attention to dosage regimens, nephrotoxicity and ototoxicity still cause concern. In the present study, we tested whether side effects of aminoglycoside therapy could be limited by expression of prokaryotic genes of antibiotic resistance in vivo. We characterized the acute and tissue-specific toxicity of hygromycin B in transgenic mice bearing the hygromycin B phosphotransferase (hygR) gene under control of a constitutive promoter. We characterized the tissue-specific expression of hygR mRNA and also investigated the acute toxicity of hygromycin B in hygR and wild-type mice. The hygR mRNA reached its highest levels in brain and reached intermediate levels in spleen, muscle, kidney, liver and testis. The lowest levels were detected in heart and lungs. The hygR expression in transgenic animals caused an 89-fold increase in the approximate lethal dose of hygromycin B compared with wild-type mice. Serum biochemical analysis of hygR and wild-type mice treated with lethal doses of hygromycin B indicated liver and kidney damage measured as ALT, AST and BUN. On the morphological level, these changes led to acute tubular nephrosis in wild-type mice and acute liver damage in hygR mice. Our results show that constitutive expression of the bacterial hygR gene in transgenic mice in vivo confers resistance to hygromycin B.
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PMID:Expression of hygR in transgenic mice causes resistance to toxic effects of hygromycin B in vivo. 915 10

The acute toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D), a herbicide, was studied in chicks dosed with 100, 300, 500, or 600 mg 2,4-D/kg BW, by the oral route. Clinical, laboratory, and histopathological methods were used as indicators of toxicity. After acute exposure, the herbicide decreased motor activity and induced muscular weakness and motor incoordination; decreased weight gain; increased serum creatine kinase (CK) and alkaline phosphatase (AP) activities and serum uric acid (UA), creatinine (CR), and total proteins (TP) levels; and did not change serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) activities. These changes were time- and dose-dependent and reversible. The LD50 (lethal dose 50%) calculated for oral 2,4-D in chicks was 420 mg/kg BW (385 to 483). Chromatographic analysis of the serum of the intoxicated chicks showed the presence of the herbicide; the amount found was dose- and time-dependent, increasing from 2 to 8 h after exposure and decreasing afterwards. Histopathological post-mortem studies conducted on intoxicated chicks showed hepatic (vacuolar degeneration of the hepatocytes), renal (tubular nephrosis), and intestinal (hemorrhagic) lesions. Taken together, the observed alterations mainly reflected kidney and muscle tissue damage, although hepatic toxicity may also have occurred after acute 2,4-D intoxication.
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PMID:Acute 2,4-dichlorophenoxyacetic acid intoxication in broiler chicks. 956 31

We report a patient, a 23-year-old man, who was a hepatitis B virus(HBV) carrier complicated with nephrotic syndrome. He was admitted to our hospital because of generalized edema and massive ascites. Laboratory data on admission were as follows: proteinuria 9,850 mg/day, Cr 2.7 mg/dl, BUN 73 mg/dl, albumin 1.9 g/dl, cholesterol 501 mg/dl, GOT 23 IU/l, GPT 19 IU/l, HBsAg(+), and HBeAg(222.7). Since his nephrotic symptoms were seriously complicated with renal failure, we selected steroid therapy for nephrosis preference. His renal function was improved and the urinary protein decreased immediately, but his liver function deteriorated. The renal biopsy revealed focal mesangial proliferative glomerulonephritis. Immunofluorescent examination revealed slight deposits of IgG, IgM, and C3 along the glomerular basement membrane and mesangial matrix. He was not compliant and often stopped taking the steroid therapy, thereby causing nephrosis to recur each time. After all, nephrotic symptoms have been well-controlled with cyclosporin and steroid. In spite of the seroconversion of HB virus by formation of HBe antibody, mutant HBV infection continued. The fact that liver biopsy revealed severe lymphoid infiltration at the portal area suggested chronic active hepatitis. His clinicopathologic course suggests that HBV-associated nephropathy does not always remit as there are some cases in whom hepatitis remains in an active state even after seroconversion, due to its mutant status. In these cases, the long-term prognosis of HBV nephropathy has not been defined. Further study is necessary to establish the optimal treatment for HB nephropathy in adults.
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PMID:[A case of hepatitis B virus carrier complicated with nephrotic syndrome]. 1099 20

In this study the short term (3 months) toxicological effects of varying levels of Catha edulis leaves were examined on the plasma concentration of liver enzymes and the histopathology of tissue sections of various organs including the liver, kidneys, spleen and testis. Both the biochemical and histopathological data demonstrated, initial signs of Catha edulis toxicity. Our results show a significant increase in plasma levels of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) with all levels of Catha edulis leaves tested and throughout the treatment period. The increase of ALP was more prominent than that of ALT. The plasma levels of aspartate aminotransferase (AST) were only moderately increased at the higher dose (30%) in the later stages of treatment. In addition, a time-dependent gradual increase in indirect bilirubin with a concomitant decrease in direct bilirubin levels was observed with the 30% Catha edulis with no signs of haemolysis. The histopathology of tissue sections of the liver displayed evidence of congestion of the central liver veins as well as acute hepatocellular degenerative and regenerative activities in the tissue sections obtained from animals treated with both 20% and 30% Catha edulis. Similarly, histopathological examination of the tissue sections of the kidneys showed some lesions, and the degree of the lesion increased as the dose of Catha edulis leaves increased including: the presence of fat droplets particularly seen in the upper cortical tubules; acute cellular swelling; hyaline tubules; and acute tubular nephrosis. In contrast, Catha edulis treatment did not affect the spleen and increased the rate of spermatogenesis in male rabbits with the spermatozoa being quite evident, the Leydig cells were in good condition and were not affected by the doses given.
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PMID:Investigation into the toxicological effects of Catha edulis leaves: a short term study in animals. 1193 13

Chloroform extract of Prunus africana (Hook f. (Rosaceae) did not cause clinical signs or pathology in rats at daily oral doses of up to 1,000 mg/kg for 8 weeks. The extract caused marked clinical signs, organ damage and a 50% mortality rate at a dose of 3.3 g/kg for 6 days. The main lesions observed at this dose were marked centrilobular hepatocellular degeneration and necrosis, diffuse nephrosis, myocardial degeneration, lymphocytic necrosis and neuronal degeneration. The morphological damage in these tissues caused a corresponding rise in blood biochemical parameters namely, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase and blood urea nitrogen. The target organs of toxicity of this extract are the liver, kidney and heart. Overt toxicity occurred only after the administration of multiple doses of 3.3 g/kg body weight. These findings confirm the suitability of this extract for therapeutic use, since the doses used in the therapy of prostate gland are much lower than those used in this study and would therefore not be expected to cause pathological changes.
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PMID:Toxicity of chloroform extract of prunus africana stem bark in rats: gross and histological lesions. 1216 69

Most ecotoxicological risk assessments of wildlife emphasize contaminant exposure through ingestion of food and water. However, the role of incidental ingestion of sediment-bound contaminants has not been adequately appreciated in these assessments. This study evaluates the toxicological consequences of contamination of sediments with metals from hard-rock mining and smelting activities. Lead-contaminated sediments collected from the Coeur d'Alene River Basin in Idaho were combined with either a commercial avian maintenance diet or ground rice and fed to captive mute swans (Cygnus olor) for 6 weeks. Experimental treatments consisted of maintenance or rice diets containing 0, 12 (no rice group), or 24% highly contaminated (3,950 microg/g lead) sediment or 24% reference (9.7 microg/g lead) sediment. Although none of the swans died, the group fed a rice diet containing 24% lead-contaminated sediment were the most severely affected, experiencing a 24% decrease in mean body weight, including three birds that became emaciated. All birds in this treatment group had nephrosis; abnormally dark, viscous bile; and significant (p <or= 0.05) reductions in hematocrit and hemoglobin concentrations compared to their pretreatment levels. This group also had the greatest mean concentrations of lead in blood (3.2 microg/g), brain (2.2 microg/g), and liver (8.5 microg/g). These birds had significant (alpha = 0.05) increases in mean plasma alanine aminotransferase activity, cholesterol, and uric acid concentrations and decreased plasma triglyceride concentrations compared to all other treatment groups. After 14 days of exposure, mean protoporphyrin concentrations increased substantially, and mean delta-aminolevulinic acid dehydratase activity decreased by more than 95% in all groups fed diets containing highly contaminated sediments. All swans fed diets that contained 24% lead-contaminated sediment had renal acid-fast intranuclear inclusion bodies, which are diagnostic of lead poisoning in waterfowl. Body weight and hematocrit and hemoglobin concentrations in swans on control (no sediment) and reference (uncontaminated) sediment diets remained unchanged. These data provide evidence that mute swans consuming environmentally relevant concentrations of Coeur d'Alene River Basin sediment developed severe sublethal lead poisoning. Furthermore, toxic effects were more pronounced when the birds were fed lead-contaminated sediment combined with rice, which closely resembles the diet of swans in the wild.
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PMID:Toxicity of lead-contaminated sediment to mute swans. 1271 82


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