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)

The protective effect of pyridoxine-2-oxoglutarate (ACP) was studied on CCl4-intoxicated rats. A sensitive improvement of hepatic conditions was shown in ACP-treated rats as compared with untreated ones and rats treated with 2-oxoglutarate and pyridoxine. Serum GOT, GPT, OCT activities, composition of serum proteins, liver mitochondria respiratory control index and liver microsomes oxidizing activity were tested. The antiketotic properties of ACP were also demonstrated in Streptozotocin treated rats.
 ...
PMID:Effect of ACP (pyridoxine-2-oxoglutarate) on CCl4 intoxication and in streptozotocin-induced ketosis in rat. 15 Jul 79

In a retrospective study it was investigated in which a course the septicemia appears during the first year of life and which laborchemical and immunological findings are typical for the specific manifestation and can be used for the diagnosis. 27 sucklings with septicemia were admitted at our hospital during 1976-1982. As the clinical course we found: the acute septicemia with pronounced shocksymptoms (Septic-Toxic-Course, STC), the septicemia with a tardy course and hematogenous dispersion of bacteria in one organsystem, namely in the brain (Meningoencephalitis), in the bone (Osteomyelitis) and in the soft tissue (Phlegmon), the septicemia with a tardy course and forms a septicopyemia with secundary dispersion of bacteria in multiple organsystems. Only STC and septicopyemia show the symptoms which are lead back with the dispersion of bacteria. By the septicemia with a tardy course and hematogenous dispersion of bacteria in one organsystem the clinical symptoms are determined only in the infected organ. As the only course of septicemia the STZ shows laborchemically in the blood a damage to the livercells with a constant elevated levels of plasmaencyms GOT, GPT and LDH; this findings can be used for a diagnostic criterion. By septicopyemia, meningitis and osteomyelitis the findings of sepsis exist in the blood but are rare by phlegmon. By septicemia with a tardy course (2, 3) a humoral and/or cellular immundeficiency exist. This is a point of application for therapy to give biological antibody with a large spectrum.
 ...
PMID:[The septic state in infancy]. 408 25

The impact of type 1 diabetes mellitus on liver gamma-glutamyltranspeptidase, a premalignant marker, was studied. Diabetes was induced in male Sprague Dawley and Fischer 344 rats by administration of Streptozotocin, which produced a stable and moderately severe diabetic state. In liver homogenates, gamma-glutamyltranspeptidase was increased over control levels: 1.2, 8.1 and 13.2 fold in Sprague-Dawley rats; 4.8, 58.4 and 84.7 fold in Fischer 344 rats; at 1, 3 and 6 weeks following Streptozotocin treatment. In plasma membranes isolated from the livers of Fischer 344 rats, gamma-glutamyltranspeptidase was increased over control levels: 5.6, 75 and 127 fold at weeks 1, 3 and 6 following Streptozotocin treatment. The relative specific activity of 5'-nucleotidase was found to be similar: 9-14, indicating comparable degrees of plasma membrane purity. Plasma glutamate-pyruvate transaminase levels were minimally and similarly affected at all time points indicating lack of association of increasing gamma-glutamyltranspeptidase activity with overt liver damage. Thyroid hormone replacement, with both T3 (0.6 micrograms/Kg) once a day and T4 (6.0 micrograms/kg) twice a day for three days elicited a further 30% increment in enzyme activity. Insulin replacement (20-40 units/200 g body weight) twice a day for five days reduced enzyme activity 51% at week 6. This was associated with an increase in gamma-glutamyltranspeptidase in the plasma from 14 fold over control levels in the diabetic state at week 6 to 53 fold over control levels after insulin replacement at week 6. It is proposed that the diabetes-induced increase in gamma-glutamyltranspeptidase is reduced by an insulin-directed shedding of the enzyme into the plasma.
 ...
PMID:The impact of type I diabetes on rat liver gamma-glutamyltranspeptidase. 786 3

Streptozotocin-diabetic and non-diabetic rats were given vanadyl sulphate in drinking water at concentrations of 0.5-1.5 mg/ml for one year. It was found that vanadyl treatment did not produce persistent changes in plasma aspartate aminotransferase, alanine aminotransferase, and urea, specific morphological abnormalities in the brain, thymus, heart, lung, liver, spleen, pancreas, kidney, adrenal, or testis, or abnormal organ weight/body weight ratio for these organs in either non-diabetic or diabetic animals. Treatment significantly reduced the incidence of the occurrence of urinary stones in non-diabetic rats. In diabetic animals vanadyl treatment significantly reduced the mortality rate and prevented the elevation of plasma levels of alanine aminotransferase and urea, the increases in organ size, and the occurrence of megacolon but did not affect the development of renal and testicular tumours. Plasma and tissue concentrations of vanadium were determined and found to have the following order of distribution: bone > kidney > testis > liver > pancreas > plasma > brain. Vanadium was retained in these organs at 16 weeks following vanadyl withdrawal while the plasma levels were beneath detection limits. It is concluded that vanadyl sulphate at antidiabetic doses is not significantly toxic to rats following a one-year administration in drinking water, but vanadium may be retained in various organs for months after cessation of treatment.
 ...
PMID:Toxicity studies on one-year treatment of non-diabetic and streptozotocin-diabetic rats with vanadyl sulphate. 787 Jun 97

Diabetes is known to potentiate thioacetamide (TA)-induced liver injury via enhanced bioactivation. Little attention has been given to the role of compensatory tissue repair on ultimate outcome of hepatic injury in diabetes. The objective of this study was to investigate the effect of diabetes on TA-induced liver injury and lethality and to investigate the underlying mechanisms. We hypothesized that hepatotoxicity of TA in diabetic rats would increase due to enhanced bioactivation-mediated liver injury and also due to compromised compensatory tissue repair, consequently making a nonlethal dose of TA lethal. On day 0, male Sprague-Dawley rats (250-300 g) were injected with streptozotocin (STZ, 60 mg/kg ip) to induce diabetes. On day 10 the STZ-induced diabetic rats and the nondiabetic rats received a single dose of TA (300 mg/kg ip). This normally nonlethal dose of TA caused 90% mortality in the STZ-induced diabetic rats. At various times (0-60 h) after TA administration, liver injury was assessed by plasma alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), and liver histopathology. Liver function was evaluated by plasma bilirubin. Cell proliferation and tissue repair were evaluated by [(3)H]thymidine ((3)H-T) incorporation and proliferating cell nuclear antigen (PCNA) assays. In the nondiabetic rat, liver necrosis peaked at 24 h and declined thereafter toward normal by 60 h. In the STZ-induced diabetic rat, however, liver necrosis was significantly increased from 12 h onward and progressed, culminating in liver failure and death. Liver tissue repair studies showed that, in the liver of nondiabetic rats, S-phase DNA synthesis was increased at 36 h and peaked at 48 h following TA administration. However, DNA synthesis was approximately 50% inhibited in the liver of diabetic rats. PCNA study showed a corresponding decrease of cell-cycle progression, indicating that the compensatory tissue repair was sluggish in the diabetic rats. Further investigation of tissue repair by employing equitoxic doses (300 mg TA/kg in the non-diabetic rats; 30 mg TA/kg in the diabetic rats) revealed that, despite equal injury up to 24 h following injection, the tissue repair response in the diabetic rats was much delayed. The compromised tissue repair prolonged liver injury in the diabetic rats. These studies suggest that the increased TA hepatotoxicity in the diabetic rat is due to combined effects of increased bioactivation-mediated liver injury of TA and compromised compensatory tissue repair.
 ...
PMID:Enhanced hepatotoxicity and toxic outcome of thioacetamide in streptozotocin-induced diabetic rats. 1089 50

Streptozotocin (STZ) has drawn attention as a potential source of oxidative stress, which induces genotoxicity. We investigated the effects of STZ on DNA damage in the liver and kidney, as well as the protective effects of antioxidants, by using the alkaline single-cell gel electrophoresis assay, and by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (8-OHdG) to dG. A single intraperitoneal injection of STZ (150 mg/kg) increased serum levels of glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and blood urea nitrogen (BUN), and also caused DNA damage in the liver and kidney, which recovered slowly with time. Antioxidants,(ascorbic acid, trolox and probucol) prevented the STZ-induced elevation of DNA damage in the liver and kidney and inhibited the increase in serum levels of AST, ALT and BUN. Thus ascorbic acid, trolox, and probucol protected the mice against STZ-induced DNA damage that might contribute to the development of hepatic or renal disease.
 ...
PMID:DNA damage and the effect of antioxidants in streptozotocin-treated mice. 1206 20

Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, and its metabolites have been reported to protect against oxidative DNA damage in vitro. Streptozotocin (STZ) has drawn attention as a potential source of oxidative stress that induces genotoxicity. In order to elucidate the antioxidative effects of fluvastatin in vivo, we investigated the effects of 7-day treatment with fluvastatin on DNA damage in STZ-treated mice, as well as the effects of the main fluvastatin metabolites (M2, M3 and M4) and other inhibitors of the same enzyme, pravastatin and simvastatin. Protective effects against DNA damage in the liver and kidney from STZ-treated mice were assessed by the single-cell gel electrophoresis assay, and by detecting 8-hydroxy-2'-deoxyguanosine. A single intraperitoneal injection of STZ (150 mg/kg) increased serum levels of glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and blood urea nitrogen (BUN), and also caused DNA damage in the liver and kidney. Fluvastatin and its metabolites prevented the STZ-induced elevation of DNA damage and inhibited the increase in serum levels of AST, ALT and BUN. Fluvastatin and its metabolites showed protective effects against DNA damage as potent as that of the reference antioxidants (ascorbic acid, trolox and probucol) though pravastatin and simvastatin still lacked protective activity. Fluvastatin protected the mice against STZ-induced DNA damage, and may reduce the risk of oxidative stress in vivo.
 ...
PMID:Antioxidative effects of fluvastatin and its metabolites against DNA damage in streptozotocin-treated mice. 1238 3

The formation of advanced glycation end products (AGEs) on extracellular matrix components leads to accelerated increases in collagen cross linking that contributes to myocardial stiffness in diabetes. This study determined the effect of the crosslink breaker, ALT-711 on diabetes-induced cardiac disease. Streptozotocin diabetes was induced in Sprague-Dawley rats for 32 weeks. Treatment with ALT-711 (10 mg/kg) was initiated at week 16. Diabetic hearts were characterized by increased left ventricular (LV) mass and brain natriuretic peptide (BNP) expression, decreased LV collagen solubility, and increased collagen III gene and protein expression. Diabetic hearts had significant increases in AGEs and increased expression of the AGE receptors, RAGE and AGE-R3, in association with increases in gene and protein expression of connective tissue growth factor (CTGF). ALT-711 treatment restored LV collagen solubility and cardiac BNP in association with reduced cardiac AGE levels and abrogated the increase in RAGE, AGE-R3, CTGF, and collagen III expression. The present study suggests that AGEs play a central role in many of the alterations observed in the diabetic heart and that cleavage of preformed AGE crosslinks with ALT-711 leads to attenuation of diabetes-associated cardiac abnormalities in rats. This provides a potential new therapeutic approach for cardiovascular disease in human diabetes.
 ...
PMID:A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes. 1270 39

Streptozotocin (STZ)-induced diabetic (DB) mice challenged with single ordinarily lethal doses of acetaminophen (APAP), carbon tetrachloride (CCl4), or bromobenzene (BB) were resistant to all three hepatotoxicants. Mechanisms of protection against APAP hepatotoxicity were investigated. Plasma alanine aminotransferase, aspartate aminotransferase, and liver histopathology revealed significantly lower hepatic injury in DB mice after APAP administration. HPLC analysis of plasma and urine revealed lower plasma t1/2, increased volume of distribution (Vd), and increased plasma clearance (CLp) of APAP in the DB mice and no difference in APAP-glucuronide, a major metabolite in mice. Interestingly, covalent binding of 14C-labeled APAP to liver target proteins; arylation of APAP to 58, 56, and 44 kDa acetaminophen binding proteins (ABPs); and glutathione (GSH) depletion in the liver did not differ between nondiabetic (non-DB) and DB mice in spite of downregulated hepatic microsomal CYP2E1 and 1A2 proteins in the DB mice, known to be involved in bioactivation of APAP. Compensatory cell division measured via 3H-thymidine pulse labeling and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) indicated earlier onset of S-phase in the DB mice after exposure to APAP. Antimitotic intervention of liver cell division by colchicine (CLC) after administration of APAP led to significantly higher mortality in the DB mice suggesting a pivotal role of liver cell division and tissue repair in the protection afforded by diabetes. In conclusion, the resistance of DB mice against hepatotoxic and lethal effects of APAP appears to be mediated by a combination of enhanced APAP clearance and robust compensatory tissue repair.
 ...
PMID:Type 1 diabetic mice are protected from acetaminophen hepatotoxicity. 1270 Apr 23

Renal accumulation of advanced glycation end products (AGEs) has been linked to the progression of diabetic nephropathy. Cleavage of pre-formed AGEs within the kidney by a cross-link breaker, such as ALT-711, may confer renoprotection in diabetes. STZ diabetic rats were randomized into a) no treatment (D); b) treatment with the AGE cross-link breaker, ALT-711, weeks 16-32 (DALT early); and c) ALT-711, weeks 24-32 (DALT late). Treatment with ALT-711 resulted in a significant reduction in diabetes-induced serum and renal AGE peptide fluorescence, associated with decreases in renal carboxymethyllysine and RAGE immunostaining. Cross-linking of tail tendon collagen seen in diabetic groups was attenuated only by 16 weeks of ALT-711 treatment. ALT-711, independent of treatment duration, retarded albumin excretion rate (AER), reduced blood pressure, and renal hypertrophy. It also reduced diabetes-induced increases in gene expression of transforming growth factor beta1 (TGF-beta1), connective tissue growth factor (CTGF), and collagen IV. However, glomerulosclerotic index, tubulointerstitial area, total renal collagen, nitrotyrosine, protein expression of collagen IV, and TGF-beta1 only showed improvement with early ALT treatment alone. This study demonstrates the utility of a cross-link breaker as a treatment for diabetic nephropathy and describes effects not only on renal AGEs but on putative mediators of renal injury, such as prosclerotic cytokines and oxidative stress.
 ...
PMID:The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. 1295 2


1 2 3 4 5 6 Next >>