Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to investigate in the rat heart and liver the effects of an acute administration of three anthracyclines, doxorubicin, epirubicin and pirarubicin, and an anthracenedione, mitoxantrone, on the membrane peroxidative status, which was estimated by the composition of polyunsaturated fatty acids (PUFA), and on the activities of the enzymes involved in membrane repair processes and lipid hydroperoxide detoxification. Rats were injected for four consecutive days with the drugs or saline (control) and killed 24 hr after the last injection. All the drugs induced an increase in plasma thiobarbituric reactive substances and alpha-tocopherol concentrations, both expressed per milligram of plasma lipids. Plasma vitamin A was decreased by about a factor of two by all the drugs. The fatty acid profile in the heart lipids showed that the polyunsaturated species (20:4 n-6, 22:6 n-3) remained at the same or even higher levels after anthracycline treatment. This can be explained by the fact that the activities of the enzymes involved in either the recycling of membrane phospholipids, such as phospholipases A1 and A2 (EC 3.1.1.4 and EC 3.1.1.32), lysophospholipases (EC 3.1.1.5) and acylCoA:lysophosphatidylcholine acyltransferases (EC 2.3.1.23), or hydroperoxide detoxification, such as selenium-dependent glutathione peroxidase (GSH-PX, EC 1.11.1.9) and glutathione S-transferases (GSH-T, EC 2.1.5.18), were maintained at the same level of activity after the antitumoral treatment. In liver, membrane phospholipid levels of PUFA were maintained as well as the activities of phospholipid-metabolizing enzymes. GSH-PX activity was not affected whereas that of GSH-T was slightly lowered by the drugs. These results suggest that during acute antitumoral-induced lipid peroxidation of membranes, the multi-enzymatic complex of the immediate processes of repair and detoxification is fully operational, allowing the membrane to rapidly recover its functional status. The results are discussed in the context of the equivocal relationships between antitumoral-induced lipid peroxidation and cardiac disturbances.
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PMID:Heart and liver membrane phospholipid homeostasis during acute administration of various antitumoral drugs to the rat. 141 37

The purpose of this study was to investigate in rats the effects of three anthracyclines, pirarubicin, doxorubicin and epirubicin on gastric prostaglandin E2 (PGE2) metabolism and phospholipase A2 (PLA2, EC 3.1.1.4) activity. The level of the membrane precursor, arachidonic acid, and the stability of the membrane were investigated by analysis of the composition of fatty acids. Enzymatic activities involved in the turnover of membrane phospholipids such as lysophospholipase (LPase, EC 3.1.1.5) and acyl-CoA lysophosphatidylcholine: acyltransferase (ACLAT, EC 2.3.1.23), and in the detoxification of lipid hydroperoxides, selenium-dependent glutathione-peroxidase (GSH-PX, EC 1.11.1.9) were measured after injection of the drugs for 4 consecutive days. Pirarubicin does not give rise to any changes in these activities but doxorubicin and epirubicin decreased PGE2 production and the activities of PLA2, LPase and ACLAT. GSH-PX activity was not changed by any of the drugs. The decrease in PLA2 activity does not seem to be related to variations in membrane lipid composition because the total phospholipids content was unchanged. The P/S (polyunsaturated/saturated) ratio increased in the doxorubicin group and decreased in the epirubicin group, and the unsaturation index was moderately modified. Arachidonic acid was increased only in the doxorubicin group. In vitro, PLA2 activity was not inhibited by the three drugs in the micromolar range. A marked inhibition was observed at 2.5 mM for pirarubicin and at 1.0 mM for doxorubicin and epirubicin. The Lineweaver-Burk representation showed that these inhibitions were of an uncompetitive type. Pirarubicin may therefore be considered to be an anthracycline without marked side-effects on gastric mucosa. However, the in vitro inhibition of PLA2 activity by anthracyclines does not fully explain the in vitro decrease in PLA2 specific activity observed after doxorubicin and epirubicin treatment, and in this context membrane structure modifications unconnected with the lipid composition can not be excluded. In vivo these phenomena may affect PGE2 synthesis, whose level was lower in the doxorubicin and epirubicin groups than in control group.
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PMID:Effect of anthracyclines on phospholipase A2 activity and prostaglandin E2 production in rat gastric mucosa. 834 60

Certain organophosphorus esters, such as diisopropylfluorophosphate (DFP), cause delayed neuropathy by inhibition of neuropathy target esterase (NTE) keeping the neuron in normal function. In this study, effects of neurobion alone and in combination with dexamethasone on DFP-induced delayed neuropathy were evaluated. Thirty-five mice were divided into five groups, each consisting of 7 mice. Except group1 (Normal group), group 2 received normal saline and 1h later, 1 mg/kg DFP; groups 3, 4 and 5 received 150 mg/kg neurobion, 2 mg/kg dexamethasone and 150 mg/kg neurobion plus 2 mg/kg dexamethasone, respectively and 1h later 1mg/kg DFP. Twenty one days after the last injection, the mice were killed by decapitation under deep anesthesia. NTE level was determined in the brain and though there was no significant difference between the groups, neurobion and neurobion plus dexamethasone partly- not significantly (p > 0.05)- were able to prevent reduction of NTE in the brain caused by DFP. Histopathological evaluation of sciatic nerves showed that neurobion and neurobion plus dexamethasone significantly suppressed the harmful effect of DFP. We also evaluated the activity of acetylcholine esterase (AChE), concentration of glutathione (GSH), and malondialdehyde (MDA) levels in the serum. Results showed dexamethasone (p < 0.001) and dexamethasone in combination with neurobion (p < 0.01) diminished AChE activity significantly compared to the DFP group. Neurobion caused a significant increase in the GSH level (p < 0.05). No significant change was seen in MDA. It is suggested that neurobion should be added and used in the first aid equipment and techniques for exposure to organophosphorus compounds, e.g. pesticides and chemical warfare.
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PMID:Effect of vitamins B1, B6, and B12 (Neurobion) on Diisopropylfluorophosphate-induced Delayed Neuropathy in Mice. 3012 34