Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effects of Ful on cadmium (CdCl2)-induced acute liver injury in mice. Ful pretreatment (150 mg.kg-1, sc x 3 d) remarkably decreased CdCl2 (3.7 mg Cd.kg-1, iv)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Distribution of Cd to 12 organs and hepatic subcellular fractions was determined 2 h after Cd challenge. Ful pretreatment did not produce a marked shift in the distribution of Cd to various organs, but markedly altered the hepatic subcellular distribution of Cd, with more Cd bound to metallothionein (MT) in the cytosol, less in the nuclear, mitochondrial, and microsomal fractions. Ful pretreatment produced a dose-dependent increase in hepatic MT as determined by the Cd.hemoglobin assay. In conclusion, Ful protected against Cd hepatotoxicity by inducing MT, which binds Cd in the cytosol and lowers the amount of Cd available to other critical organelles and proteins.
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PMID:Protective effects of fulvotomentosides on cadmium-induced hepatotoxicity. 144 1

The influence of vitamin E on cadmium intoxication was investigated in rats. The exposure to cadmium (1 mg/kg, Cd as CdCl2.2H2O, intraperitoneally for 7 days) decreased the activity of hepatic and renal glutamic oxalacetic and glutamic pyruvic transaminases (GOT, GPT) and alkaline phosphatase (ALP) accompanied by increase in the levels of serum GOT and GPT and urinary protein. Simultaneous administration of vitamin E (5 mg/kg, intramuscularly for 7 days) reduced these Cd induced biochemical alterations. The accumulation of Cd in blood, liver and kidney also decreased significantly upon co-exposure to vitamin E. The antioxidant property of vitamin E seems to be responsible for the observed protection of Cd intoxication.
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PMID:Preventive effect of vitamin E in cadmium intoxication. 158 65

Dose- and time-related effects of Cd (II) (0.5 or 1.0 mg/kg, Cd as CdCl2.H2O, subcutaneously, daily for 48 h, 1, 3, or 6 wk) were investigated in rats. A dose-related increase in the activity of plasma alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (GOT), and alanine aminotransferase (GPT) was evident only at 6 wk, whereas an early rise in ALP and LDH was seen at 3 wk in 1.0 mg Cd group only. The hepatic and renal metallothionein (MT) induction displayed a dose- as well as time-related increase with Cd accumulation. A significant increase in hepatic Zn and renal Cu, no change in hepatic Cu, and a slight increase in renal Zn was observed. Urinary ALP and leucine aminopeptidase (LAP) showed an initial increase at 48 h, thereafter returned to near normal. A second phase of enzymuria (ALP, LAP, GOT, GPT, gamma-glutamyl transpeptidase), proteinuria, and aminoaciduria occurred at 6 wk in a dose-related manner. The urinary excretion of specific renal enzymes appeared closely related to the MT induction and organ Cd levels.
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PMID:Biochemical response to cadmium. Dose-time effect. 171 72

The susceptibility to lipid peroxidation (LPO) of liver, kidneys, brains, lungs, heart, and testes was assessed in rats administered intraperitoneally with various doses of cadmium (Cd). Dose-response studies were carried out with male Long Evans rats (12-week-old; 300 +/- 33 g) injected with 25, 125, 500, and 1250 micrograms Cd/kg as CdCl2 and sacrificed after 24 h. In time-response studies, animals were administered with 25 and 500 micrograms Cd/kg as CdCl2 and sacrificed after 2, 6, 12, 24, and 72 h. Exposure of rats to low and moderate doses of Cd by the intraperitoneal route stimulated LPO in all the tissues investigated as assessed by the measurement of thiobarbituric acid reactive substances (TBARS). Lungs and brain were the most responsive, and these tissues and liver displayed early responses following Cd exposure. Comparison of LPO to various tissue indicators (for liver: alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP); for lungs: ALP, gamma-glutamyl transpeptidase (GGT] suggested that low doses of Cd stimulated LPO without any evidence of acute damages. These results suggest that LPO is an early and sensitive consequence of Cd exposure as determined in various organs. Investigation of liver, lungs, and heart antioxidant defense system components (glutathione peroxidase (GPX), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD] revealed that GPX might be considered as a potential modulator of the Cd-induced LPO reaction in lungs and heart tissues.
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PMID:Studies on lipid peroxidation in rat tissues following administration of low and moderate doses of cadmium chloride. 182 34

The administration of sodium N-methyl-N-dithiocarboxy-D-glucamine (NaG) at 500 mg/kg, i.p., or sodium calcium diethylenetriaminepentaacetic acid (DTPA) at 632.5 mg/kg, i.p., reduces the serum enzyme levels characteristic of hepatic damage following the intravenous administration of cadmium chloride (3.5 mg CdCl2.2.5H2O/kg). Some effect on serum enzyme levels was found even when the interval between administration of cadmium chloride and that of the antagonist was as great as 4 h. The enzymes examined included aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (SGPT), and alkaline phosphatase (AP). A histopathological examination of the livers of such animals also reveals the presence of a significant protective action.
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PMID:Chelating-agent suppression of cadmium-induced hepatotoxicity. 289 Jul 68

1. The effect of an acute testicotoxic dose of cadmium (CdCl2.H2O, 2.0 mg/kg i.p.) on liver morphology and drug-metabolizing enzyme activities were studied in adult male and female rats. 2. Cd treatment to female rats caused a slight and reversible decrease in hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and aminopyrine N-demethylase (APND) activities. 3. No significant changes were noted in the liver morphology, serum alanine aminotransferase activities, enzyme induction by phenobarbital and 3-methylcholanthrene, and glucuronosyl-transferase (GT) and glutathione S-transferase (GST) activities. 4. The same Cd treatment to male rats, however, resulted in a much more pronounced and prolonged reduction in AHH and APND activities, which was attributable to a Cd-induced testicular necrosis and, hence, impairment of androgen secretion. 5. Accordingly, Cd treatment to castrated male rats did not lower the enzyme activities any further, and full recovery of activities was obtained after the administration of testosterone. 6. Both GT and GST, the two sex-independent enzymes, were not significantly affected by either Cd or gonadectomy in the male rat. 7. The present data show that a low acute dose of Cd induces chemical castration without severely altering hepatic function.
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PMID:Effects of a testicotoxic dose of cadmium on the liver and drug metabolism in the rat. 289 6

Two serum enzymes which originate from the liver under different circumstances were examined as potential biological indicators in serum for cadmium toxicity. The first of those is an enzyme that leaks from damaged liver cells. The second is an enzyme that is secreted by the normal functioning liver. Cadmium chloride was injected s.c. into male and female rats of the Wistar strain (8, 15 and 22 weeks old), at doses of 1.0, 1.5 and 2.0 mg Cd/kg body weight (in total 18 groups). Cholinesterase (CHE; EC 3.1.1.8) activity in serum was found to decrease with time after the administration of a single injection of cadmium chloride and, in all experimental groups, was significantly lower than the control values on day 2 after the injection. Glutamic pyruvic transaminase (GPT; EC 2.6.1.2) activity in serum, however, increased only in the oldest group of males receiving the high dose levels of cadmium. A time-course experiment in which male and female rats 15 weeks of age were administered 1.5 mg Cd/kg body weight showed that the serum CHE activity started to decrease on day 1 after the injection, attained the lowest level on days 2 and 3, and then recovered almost to control levels on day 5. On the other hand, the GPT activity remained at or less than control values throughout the experimental period. The results indicate that CHE activity in serum is a sensitive biological indicator for cadmium toxicity.
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PMID:Depression of serum cholinesterase activity by cadmium. 404 26

The purpose of this study was to determine whether metallothionein-I (MT-I) transgenic female mice (MT-TG) are resistant to cadmium (Cd) hepatotoxicity. Female MT-TG mice have 10- to 20-fold higher MT concentrations in liver than control mice and are more resistant to Cd-induced lethality than control mice. CdCl2 (3.7 mg Cd/kg, iv) was lethal to 73% of control mice, but only to 13% of MT-TG mice. Cd administration (3.1 mg/kg, iv) to control mice produced extensive liver injury as evidenced by 20- and 70-fold increases in serum enzyme activities of sorbitol dehydrogenase and alanine aminotransferase, respectively. MT-TG mice are considerably more resistant to Cd-induced hepatotoxicity than control mice, as evidenced by only about one-tenth the elevation in serum enzymes observed in control mice and a lower incidence of hepatocyte necrosis in MT-TG mice. To ascertain the mechanism of this protection, the distribution of Cd to various organs and the subcellular distribution of Cd in liver were determined 2 hr after Cd injection (109CdCl2, 3.5 mg Cd/kg, iv). The hepatic subcellular distribution of Cd was altered markedly in MT-TG mice, with much less Cd distributing to nuclei, mitochondria, and microsomes (25, 42, and 24% of controls, respectively), and more Cd to the cytosol (240% of controls). The increased cytosolic Cd was bound primarily to MT, as determined by G-75 gel chromatography. In addition, primary hepatocyte cultures from MT-TG mice maintained higher levels of MT than hepatocytes from control mice and were more resistant to Cd cytotoxicity than control hepatocytes. In conclusion, studies using MT-I transgenic mice demonstrate that MT protects against Cd lethality and hepatotoxicity, and this hepatoprotective effect of MT is also observed in hepatocyte cultures from MT-TG mice.
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PMID:Transgenic mice that overexpress metallothionein-I are protected from cadmium lethality and hepatotoxicity. 854 31

Sodium arsenite and cadmium chloride, were administered orally to adult female rats at 21 and 4 h prior to sacrifice. Liver, lung, skin and urinary bladder were the tissues studied. DNA damage, cytochrome P450, glutathione content (GSH), ornithine decarboxylase (ODC), serum alanine aminotransferase and heme oxygenase activity were measured. Sodium arsenite increased rat hepatic ODC activity at 1.6 and 24.6 mg/kg and hepatic heme oxygenase activity at 8.2 and 24.6 mg/kg, but did not cause any DNA damage. Cadmium chloride did not affect any of the six parameters tested. These findings suggest that sodium arsenite may be a promoter rather than an initiator of carcinogenesis.
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PMID:Arsenite, but not cadmium, induces ornithine decarboxylase and heme oxygenase activity in rat liver: relevance to arsenic carcinogenesis. 855 13

Metallothioneins (MTs) are low-molecular weight, cysteine-rich, metal-binding proteins. Pretreatment of animals with Zn increases tissue MT concentrations, and protects against Cd-induced toxicity. However, Zn treatment produces many effects in addition to increasing MT. Therefore, MT-I and -II knock-out (MT-null) mice were used to determine the roles of MT in Cd-induced hepatotoxicity and nephrotoxicity, as well as in Zn-induced protection. MT-null mice were more sensitive to CdCl2 (25 mumol/kg i.p.) hepatotoxicity, as evidenced by 25-fold increases in serum alanine aminotransferase activity, compared to 12-fold increases in control mice. Zn pretreatment (200 mumol/kg s.c. x 2 days) increased hepatic MT 80 fold in control mice but not in MT-null mice, and prevented CdCl2 hepatotoxicity in control mice only. It is concluded that MT plays a critical role in Cd-induced hepatotoxicity. In contrast to CdCl2-induced hepatotoxicity, MT-null mice were equally susceptible as controls to the Cd-MT (CdMT) (0.1-0.4 mg Cd/kg i.v.) nephrotoxicity, as evidenced by similar increases in urinary protein (up to 30-fold) and glucose excretion (up to 60-fold), as well as similar extent of proximal tubular necrosis. Zn increased renal MT (28-fold) in control mice only; however, it protected against CdMT-induced renal injury in both control and MT-null mice. These findings suggest that MT plays less of a protective role in protecting against CdMT-induced nephrotoxicity than CdCl2-induced hepatotoxicity, and that Zn-induced protection against CdMT-induced nephrotoxicity does not appear to be mediated through MT.
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PMID:Metallothionein plays less of a protective role in cadmium-metallothionein-induced nephrotoxicity than in cadmium chloride-induced hepatotoxicity. 878 54


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