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)

Diets containing 0.8, 2.53 and 8.0% field variety morning glory seed were fed to male and female rats (20 per group) in a 90-day subchronic feeding study. Gross clinical observations, body weight, and feed and water intake were recorded weekly. At 90 days, all surviving rats were autopsied, organs were weighed, and blood chemistry analyses, haematology, and bone-marrow evaluation for evidence of clastogenic effects were performed. Tissues from control (0% seed) and high-dose (8.0% seed) rats were examined histologically. Effects of morning glory seed were noted mainly in the high-dose group of both sexes. These included increases in mortality, feed consumption (on a body-weight basis), water consumption, serum alkaline phosphatase and potassium, white blood cell count, and brain and liver weights (as a percentage of body weight); body-weight gain and serum glucose were decreased. Significant changes seen in high-dose females alone were: increased haemoglobin, serum constituents (urea nitrogen, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, and ornithine carbamyl transferase), and organ weights (heart, kidney, spleen and pancreas as a percentage of body weight), and decreases in serum albumin, total protein, albumin:globulin ratio, and calcium. Significant changes occurring in high-dose males alone were: increased testicular weight (as a percentage of body weight), increased serum phosphorus, and decreased serum cholesterol. Liver degeneration in the high-dose females was greater than that in the controls. Mortality at 8.0% seed in the diet was 40% in males and 10% in females. At 0.8% seed, the only parameter that differed significantly from that of the controls was a final body-weight reduction in females without a corresponding reduction in feed consumption.
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PMID:Toxicological evaluation of morning glory seed: subchronic 90-day feeding study. 224 29

Fusarium moniliforme has been associated with several diseases including equine leukoencephalomalacia, human esophageal cancer and hepatotoxicity/hepatocarcinogenicity in laboratory animals. The potential health risks to animals and humans posed by F. moniliforme contaminated grains cannot be assessed until the toxins are identified and toxicologically evaluated. As part of a systematic approach to identifying the hepatotoxins produced by F. moniliforme, diets containing aqueous and chloroform/methanol (1:1) extracts of F. moniliforme strain MRC 826 culture material (CM) and/or the extracted CM residues were fed to male Sprague-Dawley rats for four weeks. Serum alanine aminotransferase, aspartate amino-transferase and alkaline phosphatase activities were increased after two and four weeks and microscopic liver lesions were found in those animals fed aqueous CM extract and the CM residue after chloroform/methanol extraction. Fumonisins B1 and B2 were extracted from the CM by water, but not chloroform/methanol, and were present in the toxic diets at concentrations of 93-139 and 82-147 ppm, respectively. Nontoxic diets contained less than or equal to 22 ppm fumonisin B1 and less than or equal to 65 ppm fumonisin B2.
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PMID:Comparative studies of hepatotoxicity and fumonisin B1 and B2 content of water and chloroform/methanol extracts of Fusarium moniliforme strain MRC 826 culture material. 229 36

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

Male Swiss Webster mice (25-30 g) maintained on powdered control diet, or on diets containing chlordecone (CD, 10 ppm), mirex (M, 10 ppm), or phenobarbital (PB, 225 ppm) were used in this study. At these low levels, chlorinated hydrocarbon pesticides are not toxic, they neither affect food or water consumption, nor the body weight of mice. After a 15-day dietary protocol, a single challenge dose of CHCl3 (0.1 ml/kg) was administered intraperitoneally in corn oil vehicle. Liver damage was assessed 24 hours later using serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, histopathology, and lethality. For comparison, serum enzymes were measured in a separate group of mice receiving a high dose of CHCl3 (1.0 ml/kg) alone. None of the dietary treatments alone affected any of the serum transaminases. The serum enzymes were remarkably elevated in the mice treated with CD and CHCl3. A high dose of CHCl3 (1.0 ml/kg) elevated the serum enzymes more than 10-fold over those in the mice fed normal diet receiving only the corn oil vehicle. The histopathology of the liver indicated midzonal necrosis typical of liver injury from CHCl3 and depletion of PAS positive glycogen deposits. These effects were not evident in mice treated with 0.1 ml/kg CHCl3 alone. Additional histological alterations in the livers of the CD + CHCl3 group include the degenerated cells, loss of basophilic staining characteristics, and an increased degree of cytoplasmic vacuolation. The amplification of CHCl3 hepatotoxicity by CD was also reflected by a 4.2-fold increase in lethality determined by 48-hour LD50.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amplification of chloroform hepatotoxicity and lethality by dietary chlordecone (kepone) in mice. 245 13

Diagnosis of non-A, non-B hepatitis (NANB) is made after exclusion of other known causes of hepatitis. Parenterally spread non-a, non-B hepatitis (PNANB) and enterally transmitted non-A, non-B hepatitis (ENANB) almost certainly appear to be two different diseases. The definite causative agents have not hitherto been identified. Much of our knowledge of NANB is based on (i) experimental studies on chimpanzees; and (ii) epidemiological studies. Parenterally spread non-A non-B hepatitis caused by whole blood transfusion and blood-product infusion has different incubation periods and may be caused by different agents. It is a mild disease clinically, and the majority of the patients are asymptomatic. It can be prevented only by judicious use of blood transfusion. Whenever possible, blood/blood products should be derived from individual volunteer donors who are anti-HBc sero-negative and have serum alanine transaminase of under 45 IU/l. Enterally-transmitted non-A non-B hepatitis is endemic in the Indian subcontinent, South-East Asia, North and East Africa and Latin America. Epidemic NANB is usually transmitted by water supply contaminated with feces. ENANB has a predilection for young adults. The disease is usually mild, except in pregnant women, who have a high case-fatality rate from fulminant hepatic failure. Control measures include provision of clean water supplies, safe disposal of human excreta and sound personal and food hygiene practices.
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PMID:Non-A, non-B hepatitis. 251 92

Hypoestes triflora is frequently used in Rwandese native medicine to treat hepatic diseases. Premedication with a water extract of the leaves prevented the prolongation of the barbiturate sleeping time associated with carbon tetrachloride-induced liver damage in mice. The compound responsible for this protective activity was benzoic acid. Mice previously treated with benzoic acid also showed a significant diminution of the increased GOT and GPT levels seen after carbon tetrachloride administration.
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PMID:The hepatoprotective principle of Hypoestes triflora leaves. 260 53

Cardiac output (CO), renal blood flow (RBF) and hepatic blood flow (HBF) were measured by the microsphere method before (control) and at 4 and 10 h after the induction of acute renal failure by intramuscular injection of glycerol in water-drinking, long-term saline-drinking and long-term captopril (converting enzyme inhibitor)-drinking rats. At 4 h after glycerol injection, CO, RBF and HBF significantly decreased in all three groups. At 10 h after glycerol injection, CO, RBF and HBF recovered to 88% of the respective control levels in only the saline-drinking rats, whereas CO, RBF and HBF further decreased to 53, 38 and 58% of the control levels, respectively in the captopril-drinking rats. At this time, not only acute renal failure but also hepatic disorder developed in the water-drinking and captopril-drinking rats as indicated by elevations of serum creatinine, urea nitrogen, alanine aminotransferase and other blood chemistry levels. The development of acute renal failure was not suppressed by captopril, but by long-term saline load. Thus, we conclude that the decrease in CO is an important variable of the early decrease in renal and hepatic perfusion in glycerol-induced acute renal failure, and that the early recovery of HBF as well as RBF may play an important role in preventing the development of acute renal failure.
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PMID:Cardiac output, renal blood flow and hepatic blood flow in rats with glycerol-induced acute renal failure. 260 3

The chronic oral toxicity of propiverine hydrochloride (P-4), a new anti-pollakiuria agent, was studied in beagle dogs. Groups of 6 males and 6 females were treated with P-4 at doses of 0, 0.3, 1, 3, 9 mg/kg/day for one year and thereafter 2 animals of both sexes in each group were placed on withdrawal for one month. During administration and recovery period, no death occurred in any dosed animals. As a toxic sign, only the frequency of vomiting was increased in animals of 1, 3 and 9 mg/kg/day groups. Body weight, food and water consumption were not affected by the P-4 administration. In serum chemical examinations, gamma-GTP activity was increased in both sexes of 9 mg/kg/day group at 6 month of administration. Further decrease in total and free cholesterol, triglyceride and phospholipid, increase in GPT activity were detected in some animals of 9 mg/kg/day group at 12 month of administration. In addition decreasing tendency in levels of albumin was noted in males of 9 mg/kg/day group at 9 and 12 month of administration. And also, a gradual increase in total protein level and a gradual decrease in alkaline phosphatase activity were seen in control group, but in females or males of 9 mg/kg/day group, those changes were mild. Urine pH rised slightly in females of 3 mg/kg/day group and in both sexes of 9 mg/kg/day group. No specific findings attributable to P-4 treatment were detected in ECG, heart rate, funduscopy, hematology, fecal occult blood test and necropsy. The absolute and/or relative liver weight in males of 3 and 9 mg/kg/day groups were significantly increased. Light-microscopically, the hypertrophy of hepatocytes characterized by homogenization and enlargement of cytoplasmic space, and concentric inclusions in hepatocytic cytoplasm were detected in both sexes of 3 and 9 mg/kg/day groups. Corresponding to these microscopical findings, the following changes were observed electron-microscopically, the proliferation of smooth surfaced endoplasmic reticulum in hepatocytes in both sexes of 1, 3 and 9 mg/kg/day groups, lamellar bodies in hepatocytes in females of 3 mg/kg/day group, and in both sexes of 9 mg/kg/day group, and annulate lamellae in hepatocytes were detected in one female of 9 mg/kg/day group. After the recovery period, the above mentioned abnormalities were markedly attenuated or disappeared except the changes in hepatocytes. From these results, it seemed that 9 mg/kg/day of P-4 might be safety dose.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[One-year chronic oral toxicity study of propiverine hydrochloride in dogs followed by one-month recovery]. 260 51

Water purification generates a variety of chlorinated contaminants, one of which is dichloromaleic acid (DCMA). Exposure to this compound is likely to occur in combination with other drinking water pollutants, some of which are hepatotoxic. This study was designed to examine the interactive effects of carbon tetrachloride (CCl4), a known hepatotoxin, with DCMA on liver and kidney function in the Sprague-Dawley rat. Administration of a single dose of DCMA (200-400 mg/kg, ip) caused modest dose-dependent increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and plasma urea nitrogen, as well as a marked depletion of nonprotein sulfhydryls (NPSH) in the liver, but not the kidney, by 24 hr. Pretreatment with inducers (phenobarbital or 3-methylcholanthrene) or an inhibitor (SKF 525A) of cytochrome P-450 activity failed to alter the response observed with DCMA alone. Alterations in 24-hr urine volume, osmolality, and water consumption also were observed. DCMA-mediated changes in plasma urea nitrogen and NPSH were reduced in magnitude with coadministration of CCl4 (1 ml/kg, ip), while anticipated CCl4-induced increases in ALT and AST were reduced with coexposure to DCMA. Renal slice experiments indicated that DCMA-treated rats were less able to accumulate the organic anion p-aminohippurate (PAH), whereas DCMA had no effect on accumulation of the organic cation tetraethylammonium (TEA). The combination of CCl4 and DCMA produced only additive effects on organic ion accumulation. These results suggest hepatic interaction possibly related to the metabolism of CCl4 and DCMA, resulting in renal and hepatic toxicity diminished from that observed with exposure to either agent alone.
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PMID:Effect in the rat of the interaction of dichloromaleic acid and carbon tetrachloride on renal and hepatic function. 261 81

This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process.
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PMID:Assessment in rats of the gonadotoxic and hepatorenal toxic potential of dibromochloropropane (DBCP) in drinking water. 262 Jul 97


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