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At least 217 records · Page 12Linked to original sources
PubMed1998

Inhibitory effect of MCI-186, a free radical scavenger, on cerebral ischemia following rat middle cerebral artery occlusion.

1. In this study, we investigated the effect of a radical scavenger, MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), on cerebral damage induced by rat middle cerebral artery (MCA) occlusion, and further measured the hydroxyl radical level at the ischemic border zone using a microdialysis technique. 2. MCI-186, at a dose of 3 mg/kg per 30 min, was administered as a continuous infusion two times for 30 min, starting 20 min and then 80 min after Rose Bengal injection. 3. MCI-186 significantly (P < 0.05) reduced size of cerebral damage 24 hr after MCA occlusion and significantly (P < 0.05) reduced hydroxyl radical level.

Animals↗
PubMed2003

Protective effect of 3-methyl-1-phenyl-2-pyrazolin-5-one, a free radical scavenger, on acute toxicity of paraquat in mice.

Paraquat poisoning results in damages of multiple organs including liver, kidney and lung, and antioxidants have been proven to have protective effects. As a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), was introduced to clinical use recently, its protective effect was studied on acute toxicity of paraquat in male ddY mice. When paraquat (175 mg/kg) were given orally, the survival rate was only 8% on the 6th day of paraquat ingestion in Control Group mice. Protective effect of MCI-186 was most evident and the survival rate was 42% on the 6th day and 38% on the 14th day of paraquat ingestion, respectively, when mice were treated immediately. A delay of 30 min in treatment resulted in an abrupt reduction of the survival rate. These results suggested that MCI-186 used in acute phase of paraquat intoxication might serve as a clinically available antidote for attenuating paraquat toxicity.

Animals↗
PubMed2003

Analysis of carbohydrates as 1-phenyl-3-methyl-5-pyrazolone derivatives by capillary/microchip electrophoresis and capillary electrochromatography.

The 1-phenyl-3-methyl-5-pyrazolone (PMP) method has many advantages over hitherto reported methods based on reductive amination and hydrazone formation. This short review summarizes the various aspects of the PMP method, including the principle of derivatization, the simplicity of derivatization procedure, the high sensitivities to UV monitoring and ESI-MS, and the diversity of separation modes in capillary electrophoresis, and presents a number of application data for carbohydrate analysis in biological samples by this method. It also describes successful automation of carbohydrate analysis by in-capillary derivatization with PMP and miniaturization to microchip electrophoresis with whole channel UV detection allowing rapid (within 1 min) analysis of small amounts of PMP derivatives of carbohydrates. Furthermore, it discusses the possibility of capillary electrochromatography in carbohydrate analysis as PMP derivatives, and proposes an in-capillary modification strategy for improving column efficiency and elution time reproducibility.

Antipyrine↗
PubMed1999

Involvement of free radicals in cerebral vascular reperfusion injury evaluated in a transient focal cerebral ischemia model of rat.

Free radicals have been suggested to be largely involved in the genesis of ischemic brain damage, as shown in the protective effects of alpha-phenyl-N-tert-butyl nitrone (PBN), a spin trapping agent, against ischemic cerebral injury. In the present study, the effects of PBN as well as MCI-186, a newly-developed free radical scavenger, and oxypurinol, an inhibitor of xanthine oxidase, were evaluated in a rat transient middle cerebral aretery (MCA) occlusion model to clarify the possible role of free radicals in the reperfusion injury of brain. The volume of cerebral infarction, induced by 2-h occlusion and subsequent 2-h reperfusion of MCA in Fisher-344 rats, was evaluated. The administration of PBN (100 mg/kg) and MCI-186 (100 mg/kg) just before reperfusion of MCA significantly reduced the infarction volume. In contrast, oxypurinol (100 mg/kg) failed to show any preventive effect on the infarction. These results suggest that free radical formation is involved in the cerebral damage induced by ischemia-reperfusion of MCA, and that hydroxyl radical is responsible for the reperfusion injury after transient focal brain ischemia. It is also suggested that xanthine oxidase is not a major source of free radicals.

Animals↗
PubMed2003

Determination of 1-phenyl-3-methyl-5-pyrazolone-labeled carbohydrates by liquid chromatography and micellar electrokinetic chromatography.

In this paper, the method for the derivatization of carbohydrates with 1-phenyl-3-methyl-5-pyrazolone (PMP) was simplified. One-third of the derivatization time was saved. Five monosaccharide derivatives have been well separated by MEKC and HPLC under optimized conditions. Good reproducibility could be obtained with relative standard deviation (RSD) values of the migration times within 5.0 and 2.3%, respectively. Furthermore, the developed methods have been successfully applied to the analysis of carbohydrates in Aloe powder and food. These methods are quite useful for routine analysis of monosaccharides and oligosaccharides in real samples.

Antipyrine↗
PubMed1991

The pharmacokinetics of antipyrine and three of its metabolites in the rabbit: intravenous administration of pure metabolites.

Antipyrine (AP) is a commonly used probe of oxidative metabolism. Indirect evidence demonstrates formation rate limited disposition of its metabolites. Kinetic studies using antipyrine and its major metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), and 4-hydroxyantipyrine (OHA) were completed to investigate the metabolic fate of preformed antipyrine metabolite and to demonstrate directly formation rate-limited metabolite disposition in vivo. Bolus injections of antipyrine and preformed metabolites (40-50 mg/kg) were administered to male, New Zealand white rabbits. Plasma and urine were analyzed using HPLC. These studies demonstrate that HMA, NORA, and OHA are formation rate limited in the rabbit. NORA appears to undergo further extensive oxidative and conjugative metabolism. Unknown additional peaks were detected in urine after NORA dosing but not after HMA or OHA administration. Mass spectroscopy of the unknown HPLC eluents identified potential structures of these NORA metabolites.

Animals↗
PubMed2003

Effect of ozagrel, a selective thromboxane A2-synthetase inhibitor, on cerebral infarction in rats. Comparative study with norphenazone, a free-radical scavenger.

The effects of ozagrel (CAS 82571-53-7), a thromboxane A2-synthetase inhibitor, and norphenazone (CAS 89-25-8), a free-radical scavenger, on cerebral infarction were assessed using the suture-induced middle cerebral artery occlusion (MCAO) model and a microthrombosis model. In the former model, the middle cerebral artery was occluded for 2 h, and the infarction area and volume were evaluated 24 h after the start of reperfusion. In the latter model, microthrombosis were induced by two injections of sodium laurate (interval, 2 days) into the internal carotid artery, and the neurologic deficits were evaluated on the day afer the 2nd injection. Ozagrel at 3 mg/kg decreased both the area and volume of the cortical infarction after ischemia-reperfusion of the middle cerebral artery. Ozagrel also had suppressive effects on the neurologic deficits in the microthrombosis model. Norphenazone at 1 and 3 mg/kg had no clear effects in either model. Since the suture-induced MCAO model and the microthrombosis model are models for occlusion-reperfusion of the major cerebral arteries and lacunar infarction, respectively, these results suggest a highly beneficial effect of ozagrel in the clinical therapy for stroke.

Animals↗
PubMed1998

Analysis of glucuronolactone and glucuronic acid in drug formulations by high-performance liquid chromatography.

Glucuronolactone and glucuronic acid in drug formulations and beverages are determined as 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatives using high-performance liquid chromatography. Intra-ester linkage (i.e., the lactone of glucuronolactone) is spontaneously hydrolyzed to free-acid form and is analyzed as the PMP derivative of glucuronic acid. By omitting three evaporation steps in the original derivatization procedure, the total analysis time is shortened to approximately 40 min. Reproducibility of determination is within 4.0% for all drug formulations. The present method satisfies the requirements for routine analysis in the quality control of drug formulations containing glucuronolactone or glucuronic acid.

Antipyrine↗
PubMed1998

The effect of age and sex on metabolism and urinary excretion of antipyrine.

BACKGROUND: Drug-metabolizing capacity is generally reduced in the elderly. The purpose of this investigation was to study antipyrine clearance and metabolite excretion in old subjects of both sexes. METHODS: Saliva clearance of antipyrine and the production clearances of antipyrine metabolites were studied in young and elderly volunteers of both sexes. Seventy-six elderly subjects (mean age 81 years) were compared with a group of 24 young subjects (mean age 29 years). RESULTS: After oral administration, salivary antipyrine clearance declined with age in both males and females, whether or not this variable was corrected for weight, and antipyrine half-life was significantly prolonged in elderly groups of either sex. The percentage urinary excretion of the antipyrine metabolites (hydroxymethylantipyrine, HMA; norantipyrine, NORA; and 4-hydroxyantipyrine, OHA) was reduced at 48 h in the elderly compared to young subjects by 23%, 31%, and 10%, respectively, in males, and by 41%, 41%, and 24%, respectively, in females. The formation clearance of HMA was reduced by 47% in males and by 52% in females. NORA clearance declined by 42 and 56%, respectively, in males and females. A decrease of 30% in males and 44% in females was observed in OHA clearance. CONCLUSIONS: The findings suggest that aging leads to altered disposition of antipyrine in both males and females and that the main metabolic pathways of the compound are not different in the elderly.

Administration, Oral↗
PubMed1997

Determination of antipyrine and metabolites in plasma of a patient with mild renal failure.

A method has been developed for the simultaneous determination of antipyrine and its three major metabolites in plasma of patients with renal failure. Plasma samples (500 microl) were hydrolyzed with beta-glucuronidase/aryl sulphatase. The compounds, after addition of sodium chloride, were extracted with chloroform:ethanol (90:10, v/v) in acidic medium. Chromatographic conditions comprise a C18 column, a mobile phase with 30% methanol and 70% 0.25N sodium acetate buffer (pH 5.0), a total run time of 10 minutes, and ultraviolet absorbance detection at 254 nm. Confidence limits showed 0.5 to 40.0 microg/ml(-1) linearity (r2 = 0.999); 0.1 microg/ml(-1) HMA, 0.05 microg/ml(-1) antipyrine and NORA, and 0.5 microg/ml(-1) OHA sensitivity and absolute recovery >95%. Interprecision and intraprecision expressed as coefficient of variation were <10% for all compounds investigated. The assay shows to be suitable for pharmacokinetics and drug metabolism studies after administration of a single oral dose of 500 mg of antipyrine to a patient with hypertension and chronic renal failure (CL(CR) = 34.17 ml/min(-1); 1.73 m(-2)).

Adult↗
PubMed2002

Beneficial effect of MCI-186 on hepatic warm ischemia-reperfusion in the rat.

Despite growing evidence that reactive oxygen species are responsible for deleterious effects of ischemia-reperfusion (I/R) injury of the liver, there exists, until now, no reliable antioxidant therapeutics applicable in the clinical setting. We investigated the effects of free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), using an isolated liver perfusion model to elucidate its possible therapeutic effects on hepatic warm I/R injury. Isolated livers from Wistar rats were reperfused for 120 min with an oxygenated Krebs-Henseleit bicarbonate buffer after 1 hr of warm ischemia. Addition of MCI-186 (1 mg/L) into the perfusate significantly improved portal flow, hepatic enzyme release into the perfusate, total bile production, histologic alteration, and malondialdehyde concentration but not sinusoidal endothelial cell function as assessed by the clearance of hyaluronic acid. MCI-186 seems to have protective effects against hepatic warm I/R injury by attenuating the damage of the hepatocyte, which is the major target of oxidative damage in this model.

Animals↗
PubMedDate not supplied

Protective effects of a free radical scavenger, MCI-186, on high-glucose-induced dysfunction of human dermal microvascular endothelial cells.

Functional damage to microvascular endothelial cells by hyperglycemia is thought to be one of the critical risk factors in the impaired wound healing seen with diabetes mellitus. It is also thought that free radical stress plays a significant role in this endothelial cell dysfunction. In the present study, the effect of a free radical scavenger, MCI 186, on the endothelial cell dysfunction of cultured cells induced by high-glucose conditions was studied. Human dermal microvascular endothelial cells were cultured with high-glucose medium (50 mM) with or without MCI-186 (10 microM) for 7 days. Fifty mM mannitol was used as an osmotic control in this study. After this treatment, cell proliferation, activation of mitogen-activated protein kinase (MAPK), the level of apoptosis, and caspase-3 activation induced by removal of growth factors or tumor necrosis factor-alpha treatment were studied. High-glucose conditions significantly decreased cell proliferation and increased apoptosis levels with the activation of caspase-3 induced by growth factor removal. The high-glucose condition significantly activated MAPK. MCI-186 treatment improved cellular proliferation and reduced apoptosis and caspase-3 activation induced by high-glucose conditions. MCI-186 also inhibited the activation of MAPK. On the other hand, MCI-186 did not alter the level of apoptosis and caspase-3 activation induced by TNF-alpha treatment. In conclusion, we suggest that MCI-186 may be beneficial for improving the endothelial cell dysfunction induced by hyperglycemia.

Antipyrine↗
PubMed1985

The pharmacokinetics of mefloquine in man: lack of effect of mefloquine on antipyrine metabolism.

A method is described for the determination of the new antimalarial agent, mefloquine, in plasma and urine. After oral administration of 750 mg mefloquine to six volunteers, absorption, was apparently slow, with plasma mefloquine concentrations at 24 h (559 +/- 181 ng ml-1; mean +/- s.d.) higher than at 6 h (459 +/- 166 ng ml-1). The elimination half-life was 373 +/- 249 h, oral clearance was 5.09 +/- 2.7 1 h-1, and apparent volume of distribution was 35.7 +/- 30.7 l kg-1 (assuming 100% bioavailability). Mefloquine (750 mg) had no significant effect on salivary kinetics of antipyrine or on the metabolic clearance of antipyrine to its three main metabolites, 3-hydroxymethylantipyrine, 4-hydroxyantipyrine and norantipyrine, when antipyrine was administered either 2 h or 2 weeks after dosing with mefloquine.

Adult↗