Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetaminophen-induced toxicity has been attributed to cytochrome P-450-generated metabolites, which covalently modify target proteins. However, the mechanism of liver injury pathogenesis needs to be further elucidated. Platelet-activating factor (PAF) is one of the mediators involved in inflammatory tissue alterations associated with acute liver failure. In this study, alterations in blood PAF levels and the serum activity of PAF-acetylhydrolase (PAF-AH) were investigated over the time course of liver injury and regeneration induced by acetaminophen treatment in rats. The administration of a toxic dose of acetaminophen (3.5 g/kg) in rats caused acute hepatic injury, as evident by alterations of biochemical (serum enzymes: ALT, AST and ALP) and liver histopathological (degree of inflammation and apoptosis) indices between 20 and 40 h post-treatment. The hepatic damage was followed by liver regeneration, made evident by three independent indices ([3H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index), presenting a peak at 72 h. The PAF levels were elevated at 24 and 28 h, presenting a remarkable peak at 32 h post-treatment. PAF-AH activity presented different kinetics to that of PAF. The enzyme activity was relatively low at all time points examined before the rise in PAF activity, peaking later, at 72, 84 and 96 h. Our data demonstrate that PAF is involved in the pathogenesis of acute liver failure and in augmented compensatory liver tissue repair post-acetaminophen treatment. However, the putative role of PAF during liver toxicity and regeneration remains to be established.
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PMID:Platelet-activating factor (PAF) involvement in acetaminophen-induced liver toxicity and regeneration. 1599 53

The aim of this study was to investigate the effects of platelet-activating factor (PAF) inactivator, recombinant PAF-acetylhydrolase (rPAF-AH), on post-paracetamol treatment functional outcome of the liver in the rat. Fifty male Wistar rats were divided into two groups: the control group received a toxic dose of paracetamol (3.5 g/kg body weight [BW]) by gastric tube and the rPAF-AH-treated group received the same dose of paracetamol followed by a dose of rPAF-AH (10 mg/kg BW) intraperitoneally. The animals were sacrificed at time points of 56, 66, 72, 84, and 96 hr after paracetamol treatment. Hepatic injury was evaluated by determination of AST, ALT, and ALP activities and degree of necrosis and apoptosis. Liver regeneration was estimated by [3H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity, and hepatocyte mitotic index. Hepatic levels of malondialdehyde (MDA) and serum cholesterol/high-density lipoprotein cholesterol fraction were also measured as parameters of oxidant-antioxidant balance. The positive effects of rPAF-AH were expressed by (1) reduction of oxidative stress, (2) large decrease in hepatic injury, and (3) diminution of regenerating activity. These results indicate that the use of PAF inactivator enhances the liver's recovery from paracetamol intoxication and attenuates the severity of experimental liver injury, providing important means of improving liver function following paracetamol intoxication.
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PMID:Recombinant platelet-activating factor-acetylhydrolase attenuates paracetamol-induced liver oxidative stress, injury, and regeneration. 1716 Apr 78

Platelet-activating factor (PAF) is a potent endogenous phospholipid modulator of diverse biological activities, including inflammation. The aim of this study was to investigate the effects of PAF inactivator, recombinant PAF acetylhydrolase (rPAF-AH) on post-paracetamol treatment functional outcome of the liver in the rat. Fifty male Wistar rats were divided into two groups: the control group received by gastric tube a toxic dose of paracetamol (3.5 g/kg body weight) and the rPAF-AH-treated group received the same dose of paracetamol followed by a dose of rPAF-AH (10 mg/kg body weight) intraperitoneally. The animals were sacrificed at 8, 16, 24, 32, and 40 hr after paracetamol treatment. APAP was found to cause acute hepatic injury, evident by alterations of biochemical (serum enzymes: ALT, AST, and ALP) and liver histopathological (degree of inflammation and apoptosis) indexes, which was followed by liver regeneration evident by three independent indexes ([(3)H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity, and hepatocyte mitotic index). Hepatic levels of malondialdehyde (MDA) and serum cholesterol/HDL cholesterol fraction were also measured as parameters of oxidant-antioxidant balance. The positive effects of rPAF-AH were expressed by (1) a reduction of oxidative stress, (2) a large decrease in hepatic injury, and (3) a reduction of regenerating activity. These results suggest that PAF plays an important role in paracetamol-induced liver injury and regeneration. Furthermore, PAF inactivator enhances liver's recovery and attenuates the severity of experimental liver injury, providing important means of improving liver function following paracetamol intoxication.
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PMID:Platelet-activating factor inactivator (rPAF-AH) enhances liver's recovery after paracetamol intoxication. 1741 Apr 43

Platelet activating factor (PAF) is an ubiquitous phospholipid that acts as a mediator of numerous pathophysiological conditions, including hepatotoxicity. The present study has been conducted to evaluate the eventual role of the platelet activating factor in post-acetaminophen intoxication of liver, using ginkgolide B, BN52021, a selective PAF receptor antagonist. One group of rats was treated with a toxic dose of acetaminophen (APAP) (3.5 g/kg b.w.) (control group) and a second one with the same dose of APAP followed by a dose of ginkgolide B, BN52021 (10 mg/kg b.w.) (BN52021-treated group). The animals were killed at 8, 16, 24, 32 and 40 h after treatment. APAP was found to cause an acute hepatic injury, evident by alterations of biochemical (serum enzymes: ALT, AST and ALP) and liver histopathological (degree of inflammation and apoptosis) indices, which was followed by liver regeneration evident by three independent indices ([3H] thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index). Hepatic levels of malondialdehyde and serum cholesterol/HDL cholesterol fraction were also measured as parameters of oxidant-antioxidant balance. The protected effects of ginkgolide B were qualified during post treatment time by: (1) reduction of oxidative stress, (2) high decrease of hepatic injury, and (3) decrease of regenerating activity. These results indicate that PAF may play an important role in APAP-induced liver injury and regeneration, and that the use of ginkgolide B attenuates liver damage providing important means of improving liver function following acetaminophen intoxication.
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PMID:Platelet activating factor (PAF) antagonism with ginkgolide B protects the liver against acute injury. importance of controlling the receptor of PAF. 1793 19