Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute hepatic failure was induced in 50 male rabbits by D-galactosamine HCl (1 g per kg bw), and the effects of prostaglandin E1 on this model were investigated. Twelve hours after the administration of D-galactosamine HCl, a continuous infusion of prostaglandin E1 (2 micrograms.kg-1.h-1 or 20 micrograms.kg-1.h-1) was started. Ten animals in each group were observed until the time of death and mean survival times were compared between the groups. Five animals in each group were used for the determination of regional blood flows and brain water content. After the injections of D-galactosamine HCl, serum aspartate transaminase and alanine transaminase activity rose markedly and prothrombin time was prolonged. The administration of prostaglandin E1 did not affect these levels. However, the survival time in the prostaglandin E1 20 micrograms.kg-1.h-1 group (48.2 +/- 10.4 h) was significantly longer (p < 0.005, p < 0.01) than those in the untreated group (24.9 +/- 5.0 h) and the prostaglandin E1 2 micrograms.kg-1.h-1 group (28.1 +/- 5.8 h). Prostaglandin E1 20 micrograms.kg-1.h-1 inhibited elevations of blood urea nitrogen and creatinine and significantly inhibited the decrease of urine volume and urinary sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of prostaglandin E1 on experimental acute hepatic failure in rabbits: prostaglandin E1 prevents the development of multiple-organ failure. 805 85

Increased levels of natural benzodiazepine receptor agonists, produced in the body (endogenous) or ingested with food (exogenous) have been proposed as one of the factors causing hepatic encephalopathy in both experimental animals and human subjects. However, the divergent response of hepatic encephalopathy to benzodiazepine antagonists sheds doubt on this attractive hypothesis. Acute liver failure was induced in male Sprague-Dawley rats (n = 17) with intraperitoneal thioacetamide (600 mg/kg/day for 3 days) while 14 control rats received vehicle only. Acute liver failure developed in all treated rats (AST: 1,898 +/- 1,359 IU/L vs. controls, 45 +/- 5 IU/L, p < 0.005; bilirubin: 36 +/- 27 mumol/L vs. controls, 1.5 +/- 0.5 mumol/L, p < 0.005; centrizonal necrosis) and grade 3 or 4 hepatic encephalopathy (neurologic assessment and activity monitoring). However, benzodiazepine receptor ligand activity, measured in the supernatant of whole-brain homogenates with a [3H]flumazenil binding competition assay, was clearly increased in only 1 of 17 rats with acute liver failure compared with controls (52.7 +/- 34.1 vs. 44.3 +/- 18.9 ng diazepam equivalents/gm; NS). To evaluate whether the reported increase in benzodiazepine receptor ligand activity could be due to prolonged residence of exogenous benzodiazepine-like substances, additional rats with acute liver failure and controls were treated with diazepam (five doses of 0.5 mg/kg at 12-hr intervals by gavage). Benzodiazepine receptor ligand activity was greater in animals with acute liver failure than in controls (223 +/- 65 vs. 103 +/- 23 ng diazepam equivalents/gm; p < 0.002) 1 to 3 hr after the last diazepam dose.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Increased benzodiazepine-like activity is neither necessary nor sufficient to explain acute hepatic encephalopathy in the thioacetamide-treated rat. 804 18

Fulminant hepatic failure (FHF) is a poorly understood condition in which total liver failure occurs and is thought to be caused by a variety of conditions including Reye's syndrome, hepatitis, drug overdoses, and vascular insufficiency. While this condition is an uncommon one, it carries with it a high fatality rate and must therefore be diagnosed as rapidly as possible. Six patients have been observed over a two-year period with biopsy and/or autopsy-confirmed FHF: one with acute hepatitis B-delta; three with histories of alcoholism, two of them with cirrhosis; one with acute tylenol overdose; and one with hepatic vascular insufficiency. All of these patients, except one, exhibited a rapid, fatal downhill course after onset of symptoms. In all of these patients, a consistent elevation was observed in serum levels of aspartate aminotransferase (AST) or serum glutamate oxaloacetate transaminase (SGOT) and alanine aminotransferase (ALT) or serum glutamate pyruvate transaminase (SGPT) such that the ratio of AST to ALT was significantly greater than 1 and in serum levels of ammonia. Other liver function tests were found to be abnormal but not in so consistent a pattern, although total protein and albumin were found to be significantly decreased in all of these patients. The stereotypical elevation of the transaminases with high AST-to-ALT ratios and the rise in ammonia appear to characterize this life-threatening illness most reliably.
 ...
PMID:Serum analyte pattern characteristic of fulminant hepatic failure. 820 19

Acute liver failure is accompanied by a high rate of bacterial and septic complications. Arginine has a potent effect on the immune system and modulates bacterial clearance in septic models. We studied the effect of oral arginine supplementation on the extent of liver injury and the associated bacterial translocation in an acute liver injury model in rats. Sprague-Dawley rats were divided into normal, liver injury, and arginine supplemented groups. In the arginine group, 2% arginine was supplemented daily through a nasogastric tube for 8 d. Acute liver injury was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body wt). Samples were collected 24 h after the liver injury. In the arginine-supplemented group, alkaline phosphatase, bilirubin, and aspartate aminotransferase were reduced significantly compared with the acute liver injury control group. The results of bacterial translocation in the arginine-supplemented group showed a significantly reduced number of translocated bacteria to the liver and mesenteric lymph nodes than occurred in the acute liver injury group. The histological study of the liver in arginine-supplemented group showed scattered areas of hepatocellular necrosis and inflammatory cell infiltration, and in the acute liver injury group there were more and widespread hepatocellular necrosis and inflammatory cell infiltration. Oral supplementation of arginine in an acute liver injury model improves significantly the state of the liver injury and reduces bacterial translocation to the liver and mesenteric lymph nodes.
 ...
PMID:Oral arginine supplementation in acute liver injury. 887 48

Fulminant hepatic failure (FHF) is a severe, life-threatening disorder. Previous studies have suggested that intravenous prostaglandin treatment may improve survival in FHF. The present study was performed to further investigate the possible benefit of intravenous prostaglandin E1 (PGE1) for patients with FHF. A total of 18 patients, all excluded as candidates for hepatic transplantation, were studied. Thirteen of 18 participated in a randomized, double-blind, placebo-controlled trial. PGE1 was administered by continuous infusion at a dose of 10 to 40 microg/h as tolerated. After 48 hours of blinded treatment, 3 of 7 patients randomized to placebo were converted to open-label PGE1 for lack of biochemical and/or clinical improvement. Mean values for alanine transaminase, aspartate transaminase, total bilirubin, prothrombin time, factor V percent, factor VII percent, hepatic encephalopathy score, days from onset of symptoms to initiation of treatment, and cause of FHF were similar between treatment groups. Ten of 18 patients (55%) enrolled in this trial survived. However, survival was not different between PGE1-(60%) and placebo (50%) treated patients. The greatest predictor of survival was the number of days from onset of symptoms to hospitalization, which was significantly (P = .002) shorter for survivors (3.3 v 12.4 days), regardless of PGE1 treatment. Six of 8 patients (75%) who began PGE1 therapy and 4 of 5 placebo-treated patients (80%) hospitalized within 10 days of onset of symptoms survived. By contrast, all 5 patients who were hospitalized and subsequently began PGE1 treatment 10 days or longer after the onset of symptoms died. We conclude that early recognition and hospitalization is the most important factor in reduction of mortality from FHF. It is unclear whether PGE1 treatment is beneficial when administered during this period. However, it is apparent that PGE1 was not effective for treatment of FHF if treatment started more than 10 days after onset of this clinical syndrome.
 ...
PMID:Treatment of fulminant hepatic failure with intravenous prostaglandin E1. 972 81

Fulminant hepatic failure (FHF) is a clinical syndrome resulting from massive death of liver cells or sudden and severe impairment of liver function. The causes of FHF are diverse and the overall mortality is very high. Recently, it became clear that apoptosis of hepatocytes is the critical cause of acute hepatic failure in FHF. It is well known that a family of cysteine proteases called caspase is one of the key mediators of the apoptotic pathway. Thus, caspases are attractive potential targets for the treatment of disorders resulting from excessive apoptosis. In this report, we examined the activity of a new caspase inhibitor, Xyz 033 mp. This nonpeptide inhibitor showed broad-spectrum caspase-inhibiting activity and protected primary rat hepatocytes from apoptotic death. In a mouse model of FHF induced by concavalin A (Con A), Xyz 033 mp suppressed elevated AST and ALT and specifically reduced IL-1 beta concentration. Also, Xyz 033 mp rescued mice from lethal experimental hepatitis induced by Con A. In addition, histological examinations indicated that Xyz 033 mp protected hepatocytes from the fatal apoptogenic effect of Con A. These results suggest that Xyz 033 mp may be a candidate therapeutic agent for FHF caused by massive apoptotic death of hepatocytes.
 ...
PMID:A broad-spectrum caspase inhibitor blocks concanavalin A-induced hepatitis in mice. 1111 61

Acute hepatic failure was induced experimentally in rats by intraperitoneal injection of 2.5 mL kg(-1) carbon tetrachloride (CCl4), and the effects on the expression and function of P-glycoprotein in the liver, kidney and brain were evaluated. The CCl4 injection significantly increased the indicators of hepatic function (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase), but not of renal function (blood urea nitrogen, glomerular filtration rate). In rats with acute hepatic failure, the hepatic P-glycoprotein concentration increased 1.5-fold and the ATP concentration decreased to approximately 40% that in control rats. In contrast, P-glycoprotein concentrations in the kidney and brain and ATP concentrations in the kidney remained unchanged. The in-vivo P-glycoprotein function in these tissues was suppressed as evaluated by biliary and renal secretory clearances and brain distribution of rhodamine 123, a P-glycoprotein substrate. These findings suggest that factors other than P-glycoprotein concentration are involved in the systemic suppression of P-glycoprotein function in diseased rats. In Caco-2 cells, plasma collected from CCl4-treated rats exhibited a greater inhibitory effect on P-glycoprotein-mediated transport of rhodamine 123 than that from control rats, suggesting the accumulation of an endogenous P-glycoprotein substrate/inhibitor in the plasma of diseased rats. In fact, the plasma concentration of corticosterone, an endogenous P-glycoprotein substrate, increased 2-fold in CCl4-treated rats compared with control rats. It was demonstrated that P-glycoprotein function is systemically suppressed in rats with CCl4-induced acute hepatic failure, not only in the target organ (liver), but also in other organs (kidney and brain), although the P-glycoprotein concentration remained unchanged in the kidney and brain, and increased in the liver. In the systemic suppression of the P-glycoprotein function in the diseased state, the alteration of plasma concentrations or components of endogenous P-glycoprotein-related compounds, such as corticosterone, would likely be involved.
 ...
PMID:Expression and function of P-glycoprotein in rats with carbon tetrachloride-induced acute hepatic failure. 1142 64

Recent advances in molecular biology have made possible the identification of genetic defects responsible for Wilson's disease, Indian childhood cirrhosis and copper toxicosis in Long Evans Cinnamon rats, toxic milk mice, and Bedlington terriers. The Wilson's disease gene is localized on human chromosome 13 and codes for ATP7B, a copper transporting P-type ATPase. A genetic defect similar to that of Wilson's disease occurs in Long Evans Cinnamon rats and toxic milk mice. Familial copper storage disorders in Bedlington and West Highland white terriers are associated with early subclinical disease, and copper accumulation with subsequent liver injury culminating in cirrhosis. The canine copper toxicosis locus in Bedlington terriers has been mapped to canine chromosome region CFA 10q26. Recently, a mutated MURR1 gene was discovered in Bedlington terriers affected with the disease. Idiopathic childhood cirrhosis is biochemically similar to copper toxicosis in Bedlington terriers, but clinically much more severe. Both conditions are characterized by the absence of neurologic damage and Kayser-Fleisher rings, and normal ceruloplasmin levels. A recent study added North Ronaldsay sheep to the list of promising animal models to study Indian childhood cirrhosis. Morphologic similarities between the two conditions include periportal to panlobular copper retention and liver changes varying from active hepatitis to panlobular pericellular fibrosis, and cirrhosis. Certain copper-associated disorders, such as chronic active hepatitis in Doberman pinschers and Skye terrier hepatitis are characterized by copper retention secondary to the underlying disease, thus resembling primary biliary cirrhosis in humans. Copper-associated liver disease has increasingly being recognized in Dalmatians. Copper-associated liver diseases in Dalmatians and Long Evans Cinnamom rats share many morphologic features. Fulminant hepatic failure in Dalmatians is characterized by high serum activities of alanine aminotransferase and aspartate aminotransferase, and severe necrosis of centrilobular areas (periacinar, zone 3) hepatocytes. Macrophages and surviving hepatocytes contain copper-positive material. Liver disease associated with periacinar copper accumulation has also been described in Siamese cats. Many questions regarding copper metabolism in mammals, genetic background, pathogenesis and treatment of copper-associated liver diseases remain to be answered. This review describes the similarities between the clinico-pathological features of spontaneous copper-associated diseases in humans and domestic animals.
 ...
PMID:Animal models of copper-associated liver disease. 1276 23

Fulminant hepatic failure (FHF) is a serious clinical condition that is associated with high mortality. There is evidence that FHF is an inflammatory disease, which is supported clinically by elevated serum levels of cytokines. In an effort to develop hepatocytes with additional functions for use in our bioartificial liver (BAL) device, we focused on interleukin-1 (IL-1) blockade as a therapeutic modality. Primary porcine hepatocytes were isolated from the livers of miniature swine and then transfected with an adenoviral vector encoding human interleukin-1 receptor antagonist (AdIL-1Ra). The transfected hepatocytes secreted human IL-1Ra. These transfected hepatocytes were incorporated into a flat-plate BAL device to evaluate their efficacy in treating D-galactosamine (GalN)- induced FHF in a rat model. After extracorporeal perfusion with the BAL device containing the transfected hepatocytes, there were significant reductions in the plasma levels of hepatic enzymes (aspartate aminotransferase and alanine aminotransferase) and cytokines (IL-1 and IL-6), indicating a beneficial effect. Animal survival was significantly improved in the treated group compared to the control group. These experiments demonstrate that combining inflammatory cytokine blockade with a functional BAL device may be an effective therapeutic option in the treatment of FHF.
 ...
PMID:Treatment of fulminant hepatic failure in rats using a bioartificial liver device containing porcine hepatocytes producing interleukin-1 receptor antagonist. 1677 44

Fulminant hepatic failure (FHF) is a condition with a sudden onset of necrosis followed by degeneration of hepatocytes, without any previously established liver disease, generally occurring within hours or days. FHF is associated with a wide spectrum of neuropsychiatric alterations ranging from stupor to coma, culminating in death. In the present study FHF was induced in rats by the administration of thioacetamide (TAA). Oxidative stress is thought to play a prominent role in the pathophysiology of cerebral changes during FHF leading to the assumption that antioxidants might offer protection. Hence, in the present study the protective effect of C-Phycocyanin (C-PC), a natural antioxidant, was evaluated on TAA-induced tissue damage. C-Phycocyanin was administered intraperitoneally twice at 24 h interval (50 mg/kg body weight) along with the hepatotoxin TAA (300 mg/kg body weight). The animals were sacrificed 18 h after the second injection of TAA treatment and various biochemical parameters were analysed in liver, serum and brain tissues. These studies revealed significant prevention of TAA-induced liver damage by C-PC, as evidenced by a) increase in survival rate; b) the prevention of leakage of liver enzymes (AAT and AST) and ammonia into serum; c) increase in prothrombin time and d) liver histopathology. Ultrastructural studies of astrocytes of different regions of brain clearly showed a decrease in edema after C-PC treatment. TAA-induced histopathological lesions in different regions of the brain namely cerebral cortex, cerebellum and pons medulla were significantly reduced by the co-administration of C-PC with TAA. Further C-PC treatment resulted in a) decrease in the levels of tryptophan and markers of lipid peroxidation and b) elevation in the activity levels of catalase, glutathione peroxidase in different regions of brain. These studies reveal the potential of C-PC in ameliorating TAA-induced hepatic encephalopathy by improving antioxidant defenses.
 ...
PMID:Co-administration of C-Phycocyanin ameliorates thioacetamide-induced hepatic encephalopathy in Wistar rats. 1716 76


1 2 3 4 5 6 Next >>