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)

Changes in hepatic microsomal mixed-function oxidase enzyme levels (aniline hydroxylase, aminopyrine demethylase, glutathione S-transferase), glutathione content, total sulphydryl content, and plasma enzyme levels of aspartate transaminase, alanine transaminase and alkaline phosphatase were studied in male Swiss albino mice exposed to Salmonella typhimurium endotoxin (50-150 micrograms per mouse, LC50 141.82 micrograms). Animals exposed to the same dose of endotoxin but pretreated with protein A of Staphylococcus aureus (5 micrograms/per mouse) protected the animals from both mortality and depletion of biotransformation enzymes.
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PMID:Protein A protects mice from depletion of biotransformation enzymes and mortality induced by Salmonella typhimurium endotoxin. 268 31

In 1979, some pairs of voles (Microtus arvalis Pallas) were introduced to our laboratory from Hungary. Thereafter, they were successfully bred and increased in number, as experimental small animals for herbivorous domestic animals. They have been raised in a room and fed with pelleted feed for herbivores and chopped hay-cubes. We can change the high-fiber-containing rations from the chopped hay-cube to the alfalfa pellet that is widely available in laboratories. Regarding the breeding characteristics of the voles, the average litter size was 5.44 +/- 1.64, and the age at the first birth was 55.4 +/- 10.7 days. Some voles with white coats were found during the breeding process in our laboratory. Hematochemical characteristics of the voles were determined and the following characteristics were noted. Red blood cell counts of the voles were higher than those of other experimental animals (rat, mouse). White blood cell counts of the voles were lower than those of the other animals. The electrophoretic patterns of serum protein differed markedly from those of other experimental animals. The gamma-globulin concentrations of the voles were very low, and A/G ratios were high. Blood glucose concentrations of the voles were lower than those of the other mono-gastric experimental animals. Activities of serum enzymes (GOT, GPT, ALP) were higher than those of other experimental animals (rat, mouse, cow).
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PMID:[Biological and hematochemical characteristics of herbivorous common voles (Microtus arvalis Pallas)]. 354 56

Millions of people have been exposed to silicones because of the widespread use in consumer products such as cosmetics and toiletries, food products, household products and paints. Silicones have wide use in medical practice, including lubricants in tubing and syringes, and as implantable devices. The most prevalent silicone in medical use is polydimethylsiloxane. This study was undertaken to determine the subchronic immunotoxicologic potential of the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones did not alter the distribution of B cells and T cells in the spleen, but polyurethane perturbed the distribution of CD4+CD8+ and CD4-CD8- T cells. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, but polyurethane evoked an enhanced phagocytosis of Covaspheres by adherent peritoneal cells. Natural killer cell activity and serum complement were not altered. All silicone materials afforded modest protection to a challenge with Listeria monocytogenes that killed 40 to 58% of control mice. Host resistance to Streptococcus pneumoniae or the B16F10 tumor was not affected by any of the treatments. There is a pattern indicative of some perturbation of T cell differentiation in mice implanted with a polyurethane disk.
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PMID:Subchronic 10 day immunotoxicity of polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. 798 83

Millions of people have been exposed to silicones which are present in consumer goods such as cosmetics and toiletries, processed foods and household products. In addition, silicones have been used extensively in medical practice as a lubricant in tubing and syringes, and as implantable devices. A silicone widely used in medical practice is polydimethylsiloxane. This study was undertaken to determine the immunotoxicologic potential of long term exposure to the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity during the 180 day exposure. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein, or serum CH 50 or C3 levels. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones and polyurethane marginally reduced the level of Ig+ cells in the spleen but did not consistently alter the distribution of T cell surface markers. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, as was phagocytosis of chicken erythrocytes and Covaspheres by adherent peritoneal cells. Natural killer cell activity was depressed in all silicone treatment groups and in mice implanted with polyurethane. No silicone or polyurethane treatment group displayed altered susceptibility to a challenge with Listeria monocytogenes, Streptococcus pneumoniae or the B16F10 tumor. The only consistent effect of 180 day exposure to silicone materials or polyurethane was a modest depression of natural killer cell activity.
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PMID:Immunotoxicity of 180 day exposure to polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. 798 84

We studied changes of the complement pathway activities and the content of C3 in sera of mice, administered BeCl2 (containing 5 micrograms of Be per mouse) or CuCl2 (containing 5 micrograms of Cu per mouse) by a single subcutaneous injection. The value of the classical complement pathway activity (CH50) of the Be group 3 days after administration was significantly higher than that of the control group (P < 0.001). It was significantly lower than in the control group after 7 days (P < 0.001). On the other hand, the CH50 value of the Cu group 3 hr after administration tended to increase, however, it was significantly lower than in the control group after 7 days (P < 0.01). The change of the alternative complement pathway activity (ACH50) value of the Be group was similar to the change of the CH50 value of the group. The ACH50 value of the Cu group 3 days after administration tended to increase but it was the same as the ACH50 value of the control group after 7 days. The C3 contents of both the Be and Cu groups 3 days after administration were significantly higher than in the control group (P < 0.001). The aspartate aminotransferase (AST) activity of the Be group 7 days after administration was significantly higher than that of the control group (P < 0.01). By contrast, AST activity of the Cu group 3 hr after administration was significantly higher than in the control group (P < 0.05). The value of the alanine aminotransferase (ALT) activity of the Be group was low (P < 0.01), but that of the Cu group was high (P < 0.05), 3 hr after administration. These values of both groups after 7 days, however, were significantly higher than in the control group (P < 0.05). The AST/ALT ratio in mice was very high at 3 hr, and it remained high by 7 days after Be injection. On the other hand, the ratio of the Cu group was almost constant for 7 days after Cu injection. Thus, these values changed with relative expedition after Be injection. Therefore, we confirmed that measurements of complement activities and the content of C3 were valuable indices for assaying acute effects of Be on mice.
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PMID:[The changes of complement activities in sera of mice after subcutaneous administration of beryllium chloride]. 872 Sep 34

To improve liposome-directed therapy of liver disease and gene delivery, it would be beneficial to selectively target hepatocytes. For this purpose, conventional liposomes (CL) were labeled with asialofetuin (AF), an asialoglycoprotein. The biodistribution of AF-labeled liposomes (AF-L) in mice and their incorporation into rat hepatocytes, and their potential use in acute liver injury, were investigated. AF-L displayed a quicker plasma clearance than CL, and 25.4%, 2.7%, and 1.2% of the injected dose remained in the plasma versus 47.0%, 26.1%, and 9.5% of CL, respectively at 2, 4, and 20 hours after the injection. Total liver uptake of AF-L (73%+/-3.9%) was markedly higher (P < .005) than CL (16.5%+/-1.8%) 4 hours after the injection. Liposomal radioactivity (cpm/mg) was greatly enhanced in the liver (11-fold) during the first 4 hours after the administration of 14C-AF-L, and was much higher than in 14C-CL-injected mice (1.5-fold). In vitro incubation of isolated rat hepatocytes with 14C-AF-L or intravenous injection of 14C-AF-L in rats resulted in higher hepatocyte-bound radioactivity compared with 14C-CL (P < .01-.005). AF-L-associated 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) fluorescent signals were not only located in Kupffer cells, but also in hepatocytes, in which bile canaliculus networks were imaged. Intravenous administration of vitamin E (VE)-associated CL (VE-CL, 1 mg/mouse) significantly lowered alanine transaminase (ALT) levels in CCl4-treated mice (196+/-79 vs. 2,107+/-235 U/mL; P < .01). The ALT level in CCl4 + VE-AF-L group was decreased to 38+/-16 units/mL, which was significantly lower than the CC14 + VE-CL group (P < .05). In conclusion, labeling liposomes with AF led to a shortened liposome plasma half-life and greatly enhanced uptake of AF-L liposome by the liver. The enhanced uptake resulted from an increased incorporation of hepatocytes with AF-L liposomes. VE-associated AF liposomes further improved the protective effect of VE liposomes on CC14-induced acute liver injury in mice. Preferential hepatocyte incorporation of AF-L liposomes suggests a useful hepatocyte-targeting approach for drug delivery and gene transfection.
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PMID:Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents. 950 Jul 6

The administration of concanavalin A (Con A) (0.2 mg/mouse) into mice induced significant elevation of plasma alanine aminotransferase (ALT) at 8.5 hr after Con A treatment. CD8 mRNA, which is a marker of cytotoxic T-cell, was strongly induced at 16 and 24 hr after Con A treatment. Although pretreatment with cyclosporine A (CsA) (50 and 100 mg/kg, i.p.) inhibited Con A-induced elevation of plasma ALT, it did not inhibit Con A-induced CD8 mRNA expression. Morphological study revealed lymphoid cell infiltration in the liver, but the lymphoid cells were not present at the site of hepatocyte necrosis. These results suggest that Con A-induced CD8+ T-cell infiltration has a minimal effect in the development of hepatitis.
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PMID:Effects of concanavalin A treatment on CD8 mRNA expression in mouse liver. 980 70

The effect of Kupffer cell depression on concanavalin A (Con A)-induced cytokine mRNA expression in the liver was studied. Gadolinium chloride (GdCl3) is a commonly used Kupffer cell inhibitor. GdCl3 (40 mg/kg, i.p.) was injected into each mouse, and 24 hr later, Con A (0.2 mg/mouse) was administered. Plasma was obtained at 24 hr after Con A treatment for alanine aminotransferase (ALT) measurement. GdCl3 treatment inhibited Con A-induced elevation of ALT. However, it did not inhibit Con A-induced interleukin-2 or tumor necrosis factor-alpha mRNA expression. The present results suggest that Kupffer cells are not responsible for Con A-induced cytokine expression in the liver.
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PMID:Effect of gadolinium chloride treatment on concanavalin A-induced cytokine mRNA expression in mouse liver. 980 71

The effect of matrine (Mat) on lipopolysaccharides (LPS)-induced fatal hepatitis and tumor necrosis factor (TNF) production in Propionibacterium acnes (PA)-primed mice were studied. Mice were injected i.p. LPS (10 micrograms/mouse) 7 d after i.p. PA (0.5 ml/mouse) to induce fatal hepatitis. After i.p. LPS, serum TNF activity rose to 1657 +/- 406 kU.L-1 at 1.5 h and ALT activity increased up to 1,496 +/- 890 U.L-1 at 5 h. Six of 8 mice died within 5 h and the massive hemorrhagic necrosis of the liver was observed in all mice. Administration of Mat (10, 50 mg.kg-1, i.p., bid x 3 d) before the LPS injection markedly reduced the elevation of serum TNF and ALT activity in a dose-dependent manner, and diminished the mortality induced by LPS. Liver congestion and necrosis induced by LPS in PA-primed mice were ameliorated markedly by Mat pretreatment. Mat (62.5-250 mg.L-1) inhibited LPS-induced TNF release from PA-primed mouse peritoneal macrophage in vitro in a concentration-dependent manner. These results seggest that Mat protected PA-primed mice from the development of fatal hepatitis induced by LPS due to inhibition of TNF production.
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PMID:[Effect of matrine on mouse hepatitis and tumor necrosis factor production induced by Propionibacterium acnes/lipopolysaccharides]. 986 31

Bacterial endotoxin (lipopolysaccharide, LPS) is known to potentiate the toxicity of many hepatotoxicants. However, exposure to a sublethal dose of LPS renders animals tolerant to a lethal dose of LPS, and protects against the toxicity of some chemicals. This study was designed to examine the effects of LPS pretreatment on acetaminophen- and carbon tetrachloride (CCl(4))-induced liver injury in LPS-sensitive C3H/OuJ and LPS-resistant C3H/HeJ mice. Pretreatment of male C3H/OuJ mice with a single injection of LPS (0. 1 mg/kg, ip, for 24 h) protected against the hepatotoxic effects of acetaminophen (400 mg/kg) and carbon tetrachloride (CCl(4), 30 mg/kg), as indicated by serum alanine aminotransferase activity. In contrast, pretreatment of C3H/HeJ mice with 0.1 or 10 mg/kg LPS afforded no protection against the hepatotoxic effects of acetaminophen and CCl(4). In an attempt to determine the mechanism of LPS-induced protection against acetaminophen- and CCl(4)-induced hepatotoxicity in C3H/OuJ mice, liver cytochrome P450 was determined 24 h after LPS injection. LPS treatment caused a 26% decrease in total P450 content in C3H/OuJ but not in C3H/HeJ mice. CYP3A-catalized testosterone 6 beta-, 2 beta-, and 15 beta-hydroxylation was decreased 40% by LPS only in C3H/OuJ mice. To determine whether the differences to LPS-response in the two stains of mice is mediated by a strain-related difference in the release of cytokines, mice were pretreated with interleukin-1 (IL-1 alpha, 5 x 10(5) U/mouse), and the hepatoprotection and hepatic P450 enzymes were examined. IL-1 alpha pretreatment equally protected against the hepatotoxicity of acetaminophen and CCl(4) in both strains, and suppressed the total microsomal P450 and P450 enzyme-catalyzed testosterone hydroxylation to a similar extent. In conclusion, LPS pretreatment suppressed hepatic cytochrome P450 enzymes and protected against the hepatotoxicity of acetaminophen and CCl(4) in LPS-sensitive C3H/OuJ mice, but not in LPS-refractory C3H/HeJ mice. This protective effect of LPS appears to be mediated through the release of cytokines such as IL-1 alpha, which in turn suppresses the cytochrome P450 responsible for the activation of acetaminophen and CCl(4) to reactive metabolites.
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PMID:Endotoxin pretreatment protects against the hepatotoxicity of acetaminophen and carbon tetrachloride: role of cytochrome P450 suppression. 1092 99


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