Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Acetophenones”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,171 records · Page 65Linked to original sources
PubMed1987

High performance liquid chromatographic determination of thromboxane B2 in human serum as a methoxime-panacylester derivative.

A high performance liquid chromatographic (HPLC) method was developed to measure thromboxane B2 (TxB2) levels in human serum. Serum samples (2 mL) were extracted using solid phase extraction columns in a C 18/silica mode sequencing approach. The internal standard, 6-ketoprostaglandin F1 alpha, was added to the serum extracts. The eicosanoids were doubly derivatized, first with panacyl bromide, then with methoxyamine to form methoxime-panacyl ester derivatives. The eicosanoid derivatives were chromatographed using a reverse phase HPLC system with UV detection (254 nm). Assay linearity was demonstrated with fortified TxB2 standards in 3% bovine serum albumin over a range of 25 to 500 ng/mL (r greater than or equal to 0.994). There was no significant interday difference or bias in assay results for pooled standards at 75, 226 and 376 ng/mL concentrations (p greater than 0.05). Pooled estimates of precision at these levels indicate an assay relative standard deviation 6-9%. The HPLC assay was used to quantitate TxB2 levels in human serum. Results were consistent with previously published values when drug-free serum was analyzed to assess ex vivo TxB2 formation.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Characterization of liver enlargement induced by compound LY171883 in rats.

Compound LY171883 caused dose-related and reversible hepatomegaly in male Fischer 344 rats. Histological examination revealed hepatocellular hypertrophy with no other evidence of liver disease. There were only minor changes in serum glucose, total bilirubin, alkaline phosphatase, and alanine transaminase which were generally unrelated to dose and dissociable from the hepatomegaly. Total liver DNA increased but the DNA concentration decreased, indicating that liver growth involved a combination of hypertrophy and hyperplasia. Total liver protein and RNA increased. Hepatic mitochondrial protein content increased but cytochrome oxidase activity was not changed. There were minor changes in mitochondrial respiratory parameters; however, all the values were in the normal range and there was no indication of mitochondrial toxicity. Microsomal protein, drug-metabolizing activity, and cytochrome P-450 increased, but glucose-6-phosphatase activity was not changed. The induction of drug-metabolizing enzymes and absence of toxicity were evidence that the hepatomegaly was an adaptation to an increased functional load in the liver. An increase in catalase activity suggested that the response may have also involved peroxisomes. In addition to rats, LY171883 administration caused hepatomegaly in mice and hamsters at daily exposures exceeding 100 mg/kg. The response was not observed in guinea pigs, beagle dogs, or rhesus monkeys given maximum tolerated doses, indicating LY171883-induced hepatomegaly is not a response common to all species. The doses required to elicit hepatomegaly greatly exceeded doses that produce pharmacological efficacy in animals and those that are expected to be used clinically. Since humans will not receive doses comparable to those given rodents, and considering that the primate species tested did not experience hepatomegaly, it is unlikely that the effect observed in rodents can be extrapolated to humans.

Acetophenones↗
PubMed1988

Teratology studies of compound LY171883 administered orally to rats and rabbits.

The teratogenic potential of the leukotriene antagonist LY171883, a novel antiasthma agent, was investigated in CD rats and Dutch Belted rabbits. Mated female rats were dosed with 0, 10, 65, or 425 mg/kg/day on gestation days 6 through 15 and killed on gestation day 20. Mated female rabbits were dosed with 0, 20, 65, or 200 mg/kg/day on gestation days 6 through 18 and killed on gestation day 28. Maternal toxicity was indicated at 425 mg/kg in rats and 200 mg/kg in rabbits by depressed body weight gain and food consumption. In the rabbit study four abortions occurred at 200 mg/kg, most likely secondarily to maternal toxicity. LY171883 did not cause embryo/fetal toxicity or teratogenicity in rats or rabbits at doses up to and including those that were maternally toxic.

Acetophenones↗
PubMed1990

Effects of chronic treatment with the leukotriene D4-antagonist compound LY171883 on B6C3F1 mice.

A 2-year toxicity/oncogenicity study was done to evaluate the potential effects of the leukotriene antagonist LY171883 in B6C3F1 mice. Dietary concentrations of LY171883 during the initial 7 months of the study were 0.0, 0.005, 0.015, or 0.05% but were increased to 0.0, 0.0075, 0.0225, or 0.075% during Months 7 through 24. The estimated average daily compound intake was 0.0, 7.3, 22.5, or 80.5 mg/kg for males and 0.0, 9.2, 27.5, or 95.9 mg/kg for females. Survival was not adversely affected by treatment, however, body weight of males and females in the high dose group was significantly lower than that of controls. The chronic toxicity was localized primarily to the liver. Liver weights were increased in males in the high dose group and in females in the mid and high dose groups. Microsomal p-nitroanisole-O-demethylase activity was increased in mid and high dose females. Hepatic peroxisomal beta-oxidation was increased approximately twofold in both sexes in the high dose group only. Centrilobular eosinophilic granular change of hepatocytes was a common histopathologic finding in male and female mice in the high dose group, with the incidence and severity being greater in females. An increased incidence of hepatocellular carcinomas was observed in female mice in the mid and high dose groups. The number of male mice in the high dose group with hepatocellular carcinomas was higher than that of controls but the change was not statistically significant. Hepatocellular adenomas were increased in females in the high dose group but not in males. All groups of treated females had increased nodular hepatocellular hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetophenones↗
PubMed1990

Effects of chronic treatment with the leukotriene D4 antagonist compound LY171883 on Fischer 344 rats and rhesus monkeys.

One-year toxicity studies were done to evaluate potential toxic effects associated with chronic exposure of rats and monkeys to the leukotriene antagonist LY171883. Rats were fed dietary doses of 0.0, 0.01, 0.03, or 0.1%, equivalent to approximately 0, 5, 15, or 50 mg/kg of body weight/day. Monkeys were given daily nasogastric gavage doses of 0, 30, 75, or 175 mg/kg of body weight. No treatment-related effects occurred in physical, behavioral, ocular, food consumption, or urinalysis parameters in either species. Mild dose-related hepatotoxicity occurred in rats given approximately 15 or 50 mg/kg of LY171883. The hepatotoxicity was characterized by liver enlargement associated with induction of hepatic peroxisomal beta-oxidation and microsomal drug metabolism. Male rats also had hepatocellular fatty change, centrilobular hypertrophy of hepatocytes, and increased levels of serum alanine transaminase and total bilirubin. Other effects in rats included minimal decreases in hematocrit values, decreases in serum triglycerides and cholesterol, and increased kidney weight. The monkeys tolerated daily oral doses of LY171883 up to 175 mg/kg with only minor increases in hepatic microsomal enzyme activity and slightly increased liver and kidney weights in males. No effects occurred in monkeys given 30 mg/kg. There was no induction of hepatic peroxisomal enzymes or pathologic abnormalities in monkeys treated with LY171883. The peroxisomal inductive effect was apparently a species-related effect separate from the pharmacologic activity of leukotriene antagonism.

Acetophenones↗
PubMed1992

Effect of the peroxisome proliferator LY171883 on hepatocellular replication in female B6C3F1 mice.

LY171883 was shown to increase the incidence of hepatocellular carcinomas and other proliferative lesions in female B6C3F1 mice. This appeared to be unrelated to the induction of peroxisomal beta-oxidation. Experiments were conducted to determine the effect of dietary LY171883 for 7 or 94 days on hepatocellular replication using continuous 7-day infusion of bromodeoxyuridine. LY171883 caused a dose-related increase in hepatocyte replication during the first 7 days, with statistical significance in the two higher dose groups. There was no effect on hepatocyte replication after 94 days of treatment. Liver weight and peroxisomal beta-oxidation were increased in the two higher dose groups after 7 and 94 days, indicating there was not a general loss of hepatic responsiveness to LY171883. The data indicate that the hepatocarcinogenesis of LY171883 in female B6C3F1 mice is not associated with sustained replication in the general population of hepatocytes. It is possible that a mitogenic effect of LY171883 exerted on spontaneously initiated cells is involved in the development of the proliferative lesions; however, further work is needed to determine this.

Acetophenones↗
PubMed1990

Evidence for the involvement of phospholipase A2 in the regulation of luteinizing hormone-stimulated steroidogenesis in rat testis Leydig cells.

In this study the effects of modulating the release of arachidonic acid by phospholipase A2 (PLA2) on luteinizing hormone (LH)-stimulated testosterone production in rat testis Leydig cells have been investigated. Exogenously added PLA2 significantly stimulated both basal and LH-stimulated testosterone production. The effects of three structurally unrelated PLA2 inhibitors (dexamethasone, quinacrine and p-bromophenacyl bromide (pBPB)) were determined. Dexamethasone and quinacrine caused a dose-dependent inhibition of LH-induced testosterone production but had no effect on LH-induced cyclic AMP accumulation. Dibutyryl cyclic AMP-, and forskolin-stimulated testosterone production were also inhibited by all three inhibitors used. 22R-OH-cholesterol-stimulated testosterone production was not inhibited by quinacrine or dexamethasone showing that they were not exerting their inhibitory effect on LH-induced testosterone production by decreasing the activity of the steroidogenic enzymes. However, pBPB exerted an inhibitory effect on LH-induced testosterone and cyclic AMP production. Furthermore pBPB also inhibited 22R-OH-cholesterol-induced testosterone production illustrating that apart from its well-documented effect on PLA2, it also exerts a direct inhibitory effect on the steroidogenic enzymes. The finding that PLA2 inhibitors inhibit testosterone production without affecting cyclic AMP accumulation provides further indirect evidence for second messengers in addition to cyclic AMP being involved in the action of LH in Leydig cells. These results indicate that PLA2 is involved in LH-induced testosterone production and that cyclic AMP may exert its actions via this pathway.

Acetophenones↗
PubMed1985

Induction of nitroblue tetrazolium reduction in mouse peritoneal macrophages by tumour promoters and inhibition of the induced nitroblue tetrazolium reduction by some inhibitors.

Two polyacetates, aplysiatoxin and debromoaplysiatoxin, as well as 12-O-tetradecanoylphorbol-13-acetate (TPA), mezerein and teleocidin enhance nitroblue tetrazolium (NBT) reduction in mouse peritoneal macrophages in vitro. The ED50 values for NBT reduction of these 5 TPA-type tumor promoters were 4.2 ng/ml for TPA, 36 ng/ml for mezerein, 0.53 ng/ml for teleocidin, 1.5 ng/ml for aplysiatoxin and 108 ng/ml for debromoaplysiatoxin. The NBT reduction induced by the 5 tumor promoters is inhibited by 2 inhibitors of tumor promotion, retinoic acid and dibromoacetophenone. The possibility that tumor promotion by TPA-type tumor promoters involves similar mechanisms such as superoxide anion radicals release in cell membranes is discussed.

Acetophenones↗
PubMed1988

Effects of p-bromophenacyl bromide on neurite growth at different levels of nerve growth factor.

We have previously been shown that the phospholipase inhibitor p-bromophenacyl bromide (BPB) modifies neurite morphology and growth rate in rat dorsal root ganglion explants. Neurite extension is stimulated by 2.5 X 10(-7) M BPB but it is prevented by concentrations higher than 10(-5) M. Under our experimental conditions, no neurites appeared in the absence of added nerve growth factor (NGF). Therefore, we have tested the effect of a low BPB concentration at different levels of exogenous NGF. Thoracic and lumbar ganglia were obtained from 19.5-day-old fetal rats and were cultured for 24 h on a polyornithine substrate. Neurite growth and development of a dense halo were NGF-dependent in both ganglionic populations; however, each of them showed a characteristic dose-response curve. Incubation with BPB induced neurites in the absence of added NGF and stimulated their growth when low levels of this factor were added. In lumbar ganglia incubated with higher levels of NGF, BPB had no detectable effects. On the contrary, similarly treated thoracic ganglia showed an inhibition of neurite extension. Our findings suggest a relationship between the effects of BPB and the initial, membrane-activating actions of NGF.

Acetophenones↗
PubMed1989

Differential effects of phospholipase inhibitors in long-term potentiation in the rat hippocampal mossy fiber synapses and Schaffer/commissural synapses.

Bath application of the inhibitors of phospholipases, nordihydroguaiaretic acid (NDGA) and p-bromo-phenacyl bromide (BPB), to the rat hippocampal slices suppressed long-term potentiation (LTP) in Schaffer/commissural-CA1 pyramidal synapses. On the other hand, neither of the two inhibitors suppressed LTP in mossy fiber-CA3 pyramidal cell synapses. BPB did not suppress phosphatidylinositol-specific phospholipase C (PI-PLC) activity of the slices. These results suggested that the mechanisms of LTP were quite different in the CA1 and CA3 subfields of rat hippocampus: in CA1, the involvement of an arachidonate metabolism was strongly suggested, whereas in CA3, an arachidonic acid cascade may not be necessary for LTP.

Acetophenones↗
PubMed1992

A lipoxygenase pathway of arachidonic acid metabolism mediates FMRFamide activation of a potassium current in an identified neuron of Helisoma.

The neuropeptide FMRFamide causes a presynaptic inhibition of neurotransmitter release from neuron B5 of Helisoma. In this study we demonstrate that one of FMRFamide's actions is to activate an outwardly rectifying potassium current. Arachidonic acid also activates an outward current in B5. The phospholipase A2 inhibitor, 4-bromophenacylbromide (BPB), and nordihydroguaiaretic acid (NDGA), an inhibitor of arachidonic acid metabolism, but not indomethacin, block FMRFamide's activation of the potassium current. Taken together these data demonstrate that one of FMRFamide's presynaptic actions is to activate a potassium current through a lipoxygenase pathway of arachidonic acid metabolism.

Acetophenones↗
PubMed1994

Arachidonic acid participates in the anoxia-induced increase in mEPSC frequency in CA1 neurons of the rat hippocampus.

Patch clamp in the whole cell configuration was used to examine the effects of a variety of agents that influence arachidonic acid metabolism on vesicular glutamate release in CA1 neurons of rat hippocampal slices. As previously demonstrated, anoxia induced a significant increase in the frequency of spontaneous glutamate-mediated miniature excitatory postsynaptic currents (mEPSCs) during the first 5 min following anoxia. This increase in frequency was almost completely abolished if slices were preincubated in artificial cerebral spinal fluid (ACSF) containing the phospholipase C/A2 inhibitor, bromophenacyl-bromide (BPB; 20 microM) or the cyclooxygenase inhibitors, indomethacin (20 microM) and piroxicam (10 microM). This observation may be important to our understanding of the neuroprotective action of these agents. These data suggest that arachidonic acid (AA) and its cyclooxygenase products or by-products (oxygen free radicals) contribute to vesicular glutamate release during the early phase of anoxia.

Acetophenones↗
PubMed1995

Arachidonic acid may mediate the galanin-induced hyperpolarization in parasympathetic neurons from Necturus maculosus.

The effects of arachidonic acid (AA) and compounds that inhibit intracellular signalling pathways on membrane potential and galanin-induced hyperpolarizations were investigated in parasympathetic neurons from Necturus maculosus. Treatment for 10-90 min with 10-20 microM 4-bromophenacylbromide or 10 microM cyclosporin A caused a progressive decrease in the amplitude of galanin-induced hyperpolarizations without any change in resting membrane potential. The galanin-induced hyperpolarization was not altered following a 10-120 min treatment with the protein kinase inhibitor H-7. These results indicated that phospholipase A2 activation, but not protein kinase activation, may be required for the galanin-induced hyperpolarization. Arachidonic acid (20-100 microM) caused a concentration-dependent membrane hyperpolarization of the parasympathetic neurons and a decrease in the amplitude of the galanin-induced hyperpolarization. These data indicate that phospholipase A2-catalyzed liberation of AA may be involved in the galanin-induced membrane hyperpolarization observed in mudpuppy parasympathetic neurons.

Acetophenones↗
PubMed1994

Lipase inhibitors abolish contractions and cause depolarization in frog skeletal muscle fibres.

Single, intact frog muscle fibers were exposed to bromophenylacylbromide (BPB) or nordihydroguairetic acid (NDGA). Fibres first became unable to respond to electrical stimulation and then depolarized; this process was accelerated by repeated activation. In addition BPB, but not NDGA, eventually induced a contracture in the fibre. The contractile response to direct Ca-release from the sarcoplasmic reticulum by caffeine was unaffected by the drugs.

Acetophenones↗
PubMed1989

A basic phospholipase A from the venom of the Australian king brown snake (Pseudechis australis) showing diverse activities against membranes.

1. A basic phospholipase A (MSPA) was isolated from the venom of the Australian king brown snake, Pseudechis australis. 2. MSPA had an approximate Mr of 13,000 and consisted of a single polypeptide chain of 119 amino acid residues cross-linked by seven disulphide bridges. 3. MSPA exhibited direct haemolytic, anticoagulant and myotoxic activities. 4. Treatment of MSPA with p-bromophenacyl bromide modified a single histidine residue, resulting in complete loss of enzyme activity.

Acetophenones↗
PubMed1984

The oxygen dependence of the reduction of nitroimidazoles in a radiolytic model system.

Radiation chemical reductions using eaq- and CO2- have been carried out in the presence of oxygen with metronidazole, p-nitroacetophenone, misonidazole and three other 2-nitroimidazoles. Low concentrations of oxygen were found to effectively inhibit the reduction of the first two compounds while much higher concentrations of oxygen were required for all of the 2-nitroimidazoles. These results parallel in vitro and in vivo experiments with metronidazole and misonidazole which also indicate that the reduction of the latter is significantly less inhibited by oxygen. Kinetic modelling of the radiochemical system suggests that the explanation for the differences lies in different reactions of the nitro radical anions; it appears that the anion derived from metronidazole undergoes disproportionation while that derived from misonidazole undergoes a unimolecular decay.

Acetophenones↗