Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To predict the potential utility of calcitriol in human osteoporosis with hepatic dysfunction, we examined the effects of calcitriol and alfacalcidol in ovariectomized (OVX) aged-rats with CCl4-induced hepatic failure. In OVX+CCl4 rats, GOT, GTP, alkaline phosphatase and total bilirubin increased and hepatic enzyme activity (cytochrome b5 and P450) decreased. Repeated oral doses of calcitriol (0.1 and 0.2 microgram/kg) for 51 days inhibited a decrease in serum calcium concentration. This effect was more potent than that of alfacalcidol at the same dose. Both drugs tended to inhibit a decrease in femoral calcium contents. Calcitriol (0.2 microgram/kg) prevented a decrease in femoral bone density (dry and ash weight per volume), unlike alfacalcidol. Soft X-ray imaging analysis revealed that both drugs tended to inhibit the decrease in femoral bone density. There were no differences in the femoral bone strength between OVX+CCl4 and sham-operated rats. The serum calcitriol concentrations increased after the last doses of calcitriol, while they did not increase after the last dose of alfacalcidol. All these effects of calcitriol were related to the serum calcitriol levels. These results suggest that calcitriol, unlike alfacalcidol, may have a clinical therapeutic effect in osteoporosis with hepatic dysfunction.
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PMID:[Effects of calcitriol and alfacalcidol on an osteoporosis model in rats with hepatic failure]. 1009 6

Liver regeneration after injury with carbon tetrachloride (CCl4) followed by partial hepatectomy is a complex model involving toxicological, inflammatory, and necrotic processes. In the present study, the time-course of hepatic regenerative process was investigated in relation to hepatic stimulator substance (HSS) activity, administration of a single dose of CCl4 and partial (70%) hepatectomy in male rats. To evaluate liver injury events, the levels of serum aspartic aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were measured. Hepatic DNA synthesis reached a maximum at 36 hr after hepatectomy in contrast to the reported 24-hr and 32-hr peaks observed in nontreated hepatectomized rats. On the other hand, HSS activity appeared to peak at 28, 40, and 44 hr after hepatectomy in CCl4-treated rats, and it was quite a lot lower at 24, 32, 36, 48, and 60 hr. The hypothesis that HSS promotes liver regeneration but it does not initiate it, as other factors have been found to do, is discussed.
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PMID:Levels of hepatic stimulator substance in liver regenerating process of partially hepatectomized rats pretreated with a single dose of carbon tetrachloride. 1023 17

The potential of vanillin to potentiate the paracetamol and carbon tetrachloride (CCl4)-induced hepatotoxicity was investigated in rats. Vanillin when given alone (15 mg/kg, orally), did not modify liver function in rats as the values of serum enzymes of alkaline phosphatase (ALP) and aminotransaminases (AST and ALT) were found similar to those in the normal animals. However, when given repeatedly before the administration of the subtoxic dose of paracetamol (500 mg/kg) or CCl4 (1 ml/kg), vanillin caused liver damage, as manifested by the significant increase in the serum levels of hepatic enzymes. When tested for its possible interaction with pentobarbital (75 mg/kg, i.p.) and strychnine (0.9 mg/kg, i.p.), it caused reduction in pentobarbital-induced sleep in mice as well as preventing the animals against the lethal effect of strychnine, suggestive of an induction of microsomal drug metabolizing enzymes. These results indicate that vanillin potentiates the hepatotoxic potential of paracetamol and CCl4 in rats probably through an enzyme induction process.
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PMID:Potentiation of paracetamol and carbon tetrachloride-induced hepatotoxicity in rodents by the food additive vanillin. 1047 28

The pharmacokinetics and hepatoprotective effects of 2-methylaminoethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybip henyl-2-carboxylic acid-2'-carboxylate monohydrochloride (DDB-S) have been investigated in rats with CCl4-induced acute hepatic failure. To study the pharmacokinetics of DDB-S, rats were divided into a control group and a CCl4-intoxicated group. DDB-S 50 mg kg(-1) was administered by intravenous bolus injection to both groups of rats. In the CCl4-intoxicated rats the plasma concentrations of DDB-S were significantly higher, the area under the plasma concentration-time curve from time zero to time infinity was significantly greater (6-46 vs 3.34 mg min mL(-1)), and the total body (7.74 vs 15.0 mL min(-1) kg(-1)), renal (2.55 vs 5.10 mL min(-1) kg(-1)), nonrenal (5.07 vs 9.65 mL min(-1) kg(-1)), and biliary (1.48 vs 2.69 mL min(-1) kg(-1)) clearances were significantly slower compared with the control rats. This could be due to decreased hepatic cytochrome P450 activity and impaired kidney function induced by CCl4. To study the hepatoprotective effects of DDB-S, rats were divided into three groups, control rats and CCl4-intoxicated rats with or without DDB-S pretreatment (50 mg kg(-1) i.p.). The effects of DDB-S pretreatment on CCl4-induced liver injury were considerable; the serum levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase were significantly lower by 54.3, 44.6 and 67.2%, respectively, compared with the CCl4-intoxicated-only group. In an in-vitro study, rat hepatocytes were exposed to fresh medium containing 10 mM CCl4 and various concentrations of DDB-S (10 or 100 microg mL(-1)). The levels of alanine transaminase and aspartate transaminase in the medium were measured as an indicator of hepatocyte injury. DDB-S dose-dependently decreased the levels of alanine transaminase and aspartate transaminase compared with CCl4-intoxication only. These results indicate that DDB-S has hepatoprotective activity.
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PMID:Pharmacokinetics and hepatoprotective effects of 2-methylaminoethyl-4,4'-dimethoxy-5 ,6,5',6'dimethylenedioxybiphenyl-2-carboxylic acid-2'-carboxylate monohydrochloride in rats with CCl4-induced acute hepatic failure. 1104 90

The aim of the study was to evaluate the effect of cirrhosis on the disposition of the haemoglobin-based oxygen carrier, diaspirin cross-linked haemoglobin (DCLHb). Cirrhosis was induced in male Sprague-Dawley rats (200-250 g) by inhalational exposure to carbon tetrachloride (CCl4), over a period of 6 weeks. Pharmacokinetic evaluation was performed after a single intravenous bolus administration of DCLHb (400 mg kg(-1)). Serum biochemistry, including aspartate transaminase, alkaline phosphatase, bile acids, serum albumin, and serum creatinine, were measured in CCl4-treated (n = 6) and age-matched control (n = 6) rats. After 6 weeks, the jugular vein and carotid artery were cannulated for bolus DCLHb administration (400 mg kg(-1)) and blood sampling, respectively, in both groups of rats. Cirrhosis produced significant (P < 0.05) elevations in alkaline phosphatase (497.4 +/- 84.8 U L(-1) vs 241.2 +/- 5.1 U L(-1)), aspartate transaminase (920.5 +/- 190.9 U L(-1) vs 238.2 +/- 118.1 U L(-1)) and bile acids (333.8 +/- 77.3 mg dL(-1) vs 43.8 +/- 4.2 mg dL(-1)) compared with the control group. No significant renal dysfunction was observed as a result of CCl4 exposure. Plasma DCLHb concentrations declined approximately log-linearly. Systemic clearance of DCLHb was estimated to be 2.2 +/- 0.7 mL h(-1) in the treatment group and was slightly, but not significantly, less in the control group (3.6 +/- 1.7 mL h(-1)). There was also a trend toward a longer elimination half-life in the treatment group (4.7 +/- 2.2 h) compared with the control group (3.8 +/- 0.8 h), although this difference was not statistically significant. Cirrhosis does not significantly alter the disposition of DCLHb perhaps due to increased extra-hepatic metabolism by the reticulo-endothelial system.
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PMID:Pharmacokinetics of diaspirin cross-linked haemoglobin in a rat model of hepatic cirrhosis. 1127 13

Berberis aristata is an edible plant employed in the South Asian Traditional Medicine, particularly its fruits being used as a tonic remedy for liver and heart. In this investigation, berberine, a known compound from this plant, was studied for its possible antihepatotoxic action in rats. Pretreatment of animals with berberine (4 mg/kg; orally twice daily for 2 days) prevented the acetaminophen- or CCl4-induced rise in serum levels of alkaline phosphatase (ALP) and aminotransaminases (AST and ALT), suggestive of hepatoprotection. Post-treatment with three successive oral doses of berberine (4 mg/kg every 6 h) reduced the hepatic damage induced by acetaminophen, while CCl4-induced hepatotoxicity was not modified, suggesting a selective curative effect against acetaminophen. Pretreatment of animals with a single oral dose of berberine (4 mg/kg) induced prolongation of the pentobarbital (60 mg/kg, i.p.)-induced sleeping time as well as increased strychnine (0.3 mg/kg; i.p.)-induced toxicity, suggestive of inhibitory effect on microsomal drug metabolizing enzymes, cytochrome P450s (CYPs).
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PMID:Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. 1144 66

Aphanamixis polystachya is a traditional medicinal plant of the Meliaceae family in India. A crude ethanolic extract of the leaf of this plant shows a beneficial effect on toxic liver injury. Its antihepatotoxic activity was evaluated on carbon tetrachloride (CCl4)-induced liver injury in a rat model. The assessment of hepatoprotective activity was evaluated by measuring the activities of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), acid phosphatase (ACP) and lactate dehydrogenase (LDH), serum total bilirubin and albumin and histology of the liver. The crude leaf extract significantly inhibits the enhanced ASAT, ALAT, ALP, ACP and LDH activities released from the CCl4-intoxicated animals. It also ameliorated the depressed value of serum albumin and the enhanced value of total bilirubin in plasma caused by CCl4 intoxication. The study showed that the crude ethanolic extract from A. polystachya leaves provided protection against acute carbon tetrachloride-induced liver damage.
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PMID:Role of plant metabolites in toxic liver injury. 1189 Jun 39

Effect of Tinospora cordifolia extract on modulation of hepatoprotective and immunostimulatory functions in carbon tetrachloride (CCl4) intoxicated mature rats is reported here. Administration of CCl4 (0.7 ml/kg body weight for 7 days) produces damage in the liver as evident by estimation of enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transminase (SGPT) and alkaline phosphatase (ALP) as well as serum bilirubin level. CCl4 administration also causes immunosuppressive effects as indicated by phagocytic capacity, chemotactic migration and cell adhesiveness of rat peritoneal macrophages. However, treatment with T. cordifolia extract (100 mg/kg body weight for 15 days) in CCl4 intoxicated rats was found to protect the liver, as indicated by enzyme level in serum. A significant reduction in serum levels of SGOT, SGPT, ALP, bilirubin were observed following T. cordifolia treatment during CCl4 intoxication. Treatment with T. cordifolia extract also deleted the immunosuppressive effect of CCl4, since a significant increment in the functional capacities of rat peritoneal macrophages (PM phi) was observed following T. cordifolia treatment. The results of our experiment suggest that treatment by T. cordifolia extract may be the critical remedy for the adverse effect of CCl4 in liver function as well as immune functions.
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PMID:Hepatoprotective and immunomodulatory properties of Tinospora cordifolia in CCl4 intoxicated mature albino rats. 1223 38

Inhibition of Kupffer cells could disrupt the sequence of events leading to organ injury by damping down the fibrogenic stimulus. To elucidate the role of Kupffer cells in liver fibrosis and cirrhosis, rats were treated with gadolinium chloride (GdCl(3)) and cirrhosis was induced by subchronic carbon tetrachoride (CCl(4)) administration. Carbon tetrachloride was administered three times per week for 8 weeks to male Wistar rats treated simultaneously with GdCl(3) (20 mg kg(-1), i.p. daily); appropriate controls were performed. Serum enzyme activities of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (gamma-GTP) and alanine aminotransferase (ALT) and bilirubin concentration increased significantly by CCl(4), whereas GdCl(3) prevented completely the increase in gamma-GTP and partially prevented the increase in ALP, ALT and bilirubins (P < 0.05). Liver glycogen was depleted by CCl(4), an effect that GdCl(3) was not capable of preventing. Moreover, gadolinium by itself depleted it. Lipid peroxidation increased about 2.5-fold by administration with CCl(4), whereas GdCl(3) preserved lipid peroxidation within normal values. Hepatic collagen increased threefold after subchronic intoxication with CCl(4) (P < 0.05) whereas GdCl(3) prevented partially (P < 0.05) the increase in collagen content, as evidenced by the liver hydroxyproline content and by the histopathological analysis. The present results suggest that Kupffer cells are needed for the production of CCl(4)-induced cirrhosis, because their inactivation with GdCl(3) prevents the disease.
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PMID:Kupffer cells are responsible for liver cirrhosis induced by carbon tetrachloride. 1266 54

Ethanol extract of Solanum nigrum LINN was investigated for its hepatoprotective activity against CCl4-induced hepatic damage in rats. The ethanol extract showed remarkable hepatoprotective activity. The activity was evaluated using biochemical parameters such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP) and total bilirubin. The histopathological changes of liver sample in treated animals were compared with respect to control.
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PMID:Effect of dried fruits of Solanum nigrum LINN against CCl4-induced hepatic damage in rats. 1460 Apr 13


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