• Archives of Pharmacal Research
• /
• 제19권5호
• /
• pp.348-352
• /
• 1996

The antioxidant efficacy of aspalatone, a new antithrombotic agent, has been recognized in the neurotoxic model and in the cardiotoxic model in proliminary studies. We examined the specific activity of antiosidnat enzyme in the rat blood following administrations of aspirin, maltol, aspirin together with maltol, salicylmaltol (major metabolite of aspalatone) and aspalatone, respectively. Our assessment showed that salicylmaltol, maltol, aspalatone enhanced antiperoxidative activity. In addition, neither aspirin nor combination of aspirin and maltol, showed any significant effect on the activity of antioxidant enzyme. Because $H_{2}$$O_{2}$ accumulation may stimulate the thrombogenesis in blood, the result suggests that the induction of blood antiperoxidative activity produced by aspalatone may have beneficial effects on the thrombogenesis.

• Journal of Pharmaceutical Investigation
• /
• 제23권3호
• /
• pp.165-177
• /
• 1993

The relationship between the plasma haloperidol (HP) concentration and clinical response, and the effects of its active metabolite, reduced haloperidol (RH) on clinical response of HP were investigated in schizophrenic patients. In clinical study I, with 17 schizophrenic patients (male 8, fermale 9) who were administered with three different fixed doses of HP (15, 30 and 50 mg/day) for 3 weeks, the concentrations of HP and RH in plasma and blood and clinical response had been checked before and every week during the study. The clinical response was evaluated by the method of brief psychiatric rating scale (BPRS), and relative improvement of clinical response based on baseline BPRS (before drug treatment) was calculated. The concentrations of HP and RH in plasma and blood were assayed by HPLC. In clinical study II, the plasma RH/HP concentration ratios were checked in 11 patients who were administered with high doses of HP, over 60 mg a day, because of the poor clinical response at usual doses of HP. Plasma HP concentration and relative improvement of BPRS at 3 week in schizophrenic patients showed a 'curvilinear' relationship, and the clinical response was improved relatively over 50% based on the baseline BPRS in the range of $5{\sim}57\;ng/ml $ of HP in plasma. Also, the plasma RH concentrations were increased nonlinearly as the plasma HP concentration increased, and in high plasma HP concentration, over 30 ng/mI, clinical response gradually decreased, while the plasma RH/HP concentration ratio increased nonlinearly. Blood partition coefficients of HP and RH were not changed according to daily HP dose and duration of drug therapy. From these results, it is noted that the higher plasma RH/HP concentration ratio, resulted from the accumulation of RH as HP concentration increased, might explain the 'curvilinear' decrease of HP clinical response.

• Toxicological Research
• /
• 제11권2호
• /
• pp.289-294
• /
• 1995

This study was designed to observe the effect of tohiene pretreatment on leukocyte variation in whole blood and the oxygen free radical generating, scavenging enzyme activities in neutrophil of bacteria infected rats. Toluene was administered 7 times intraperitoneally at levels of 9.45 mM/kg body weight to the rats and then infected with S. aureus $2\times10^7$ cfu/ml. The toluene treated-rats showed the significantly decreased numbers of lymphocyte and monocytes, but the similiar numbers of neutrophils with the control. Furthermore the increased neutrophils in blood of bacteria infected rats were reduced by the toluene pretreatment. Concomitantly the increased activities of xanthine oxidase and superoxide dismutase in neutrophil of bacteria infected rats were also decreased by the toluene pretreatment. On the other hand, injection of benzaldehyde to rats also led to similiar results in the count of leukocytes, xanthine oxidase and superoxide dismutase activities of neutrophil with those of toluene treated rats. These data suggest that toluene and its intermediate metabolite, benzaldehyde influence on the phagocytosis and defence mechanism of neutrophil.

• Asian-Australasian Journal of Animal Sciences
• /
• 제14권8호
• /
• pp.1085-1089
• /
• 2001

Metabolites, such as isopropyl alcohol (IPA) produced by rumen fermentation, were intravenously infused into a jugular vein of goats during feeding to explore the mechanism and roles of IPA in ruminating behavior (number of boli and ruminating time). Three female goats were confined in metabolism cages with a stanchion, The ruminating behavior measured by the number of ruminations, ruminating time, number of remastications, and remasticating time decreased (p<0,05) with intravenous IPA infusion. The IPA concentrations and VFA concentrations increased in the blood circulation. Our data suggest that sensitive receptors of rumination to IPA are more likely to be in an area such as the brain stem where they can respond to blood metabolite levels.

• 약학회지
• /
• 제31권3호
• /
• pp.149-153
• /
• 1987

Pyrazinamide, an amide of pyrazinoic acid, is widely used in combination with other drugs for the treatment of tuberculosis. It was attempted to observe the effect of pyridoxal on the pyrazinamide induce hyperuricemia in this study. It was observed that the values of serum transminases were not changed in mice injected pyrazinamide and pyrazinoic acid, respectively (100, 200, and 300mg/kg) compared with control. Blood urate levels were increased in mice treated with these drugs in a dose dependent manner. After pyrazinoic acid was administered intraperitoneally at a dose of 300mg/kg pretreated with 50mg/kg of pyridoxal once daily for 4 days, the blood levels of uric acid and pyrazinoic acid were decreased significantly.

• Toxicological Research
• /
• 제14권4호
• /
• pp.557-562
• /
• 1998

Allyl alcohol is metabolized in the liver through two steps, first to reactive acrolein by alcohol dehydrogenase (ADH), subsequently to acrylic acid by aldehyde dehydrogenase (ALDH). Since ethanol could compete the same enzymes to be metabolized in the liver, we have determined the plasma concentrations of allyl alcohol and ethanol followed by combined treatment. Pretreatment of rats with 2g/kg ethanol followed by ip administration of 40mg/kg allyl alcohol increased the lethality significantly. Determination of in vivo blood concentrations revealed that ethanol pretreatment caused the apparent decrease in allyl alcohol clearance, whereas acetaldehyde level in blood increased significantly by allyl alcohol treatment, as determined by head space GC analysis. Treatment of 4-methylpyrazole, an inhibitor of ADH, delayed allyl alcohol elimination significantly and reduced its lethality. Collectively, these findings suggested that reduction of allyl alcohol clearance in the presence oj ethanol was mediated through ADH competitive inhibition.

• Asian-Australasian Journal of Animal Sciences
• /
• 제18권10호
• /
• pp.1469-1474
• /
• 2005

The objective of this study was to determine the levels of nutritionally related blood metabolites, age and body weight at puberty in gilts fed on corn cob-based diet in Mukota and Landrace${\times}$Mukota crossbred gilts. Ten gilts of each of Mukota and crossbred genotypes were fed two diets for 14 weeks in a 2${\times}$2 (breed${\times}$diet) factorial treatment arrangement. A corn-cob based diet, designed to contain 2,304 kcal ME/kg, and a standard pig grower diet, were used. The corn cob constituted 20 percent of the total ration. Fortnightly, bodyweights and feed conversion ratios (FCR) were recorded. Blood samples were collected to determine blood glucose, urea and creatinine levels. The average daily bodyweight gain (ADG) in the Mukota was lower (p<0.05) than in the crossbred gilts. Crossbred gilts fed on the corn cob-based diet had lower (p<0.05) urea values from eight weeks from the start of the experiment (p<0.05) compared to Mukota gilts fed the same diet. There were no differences in blood glucose and creatinine concentrations between diets and genotypes. The lack of differences in the nutritionally-related blood metabolites suggest that corn cobs could be incorporated at 20 percent inclusion without compromising blood metabolite concentrations and age at puberty of the Mukota and Landrace${\times}$Mukota gilts.

• Journal of Ginseng Research
• /
• 제38권3호
• /
• pp.203-207
• /
• 2014

Background: There is limited understanding of the effect of dietary components on the absorption of ginsenosides and their metabolites into the blood. Methods: This study investigated the pharmacokinetics of the ginseng extract and its main constituent ginsenoside Rb1 in rats with or without pretreatment with a prebiotic fiber, NUTRIOSE, by liquid chromatography tandem mass spectrometry. When ginsenoside Rb1 was incubated with rat feces, its main metabolite was ginsenoside Rd. Results: When the intestinal microbiota of rat feces were cultured in vitro, their ginsenoside Rd-forming activities were significantly induced by NUTRIOSE. When ginsenoside Rb1 was orally administered to rats, the maximum plasma concentration (Cmax) and area under the plasma drug concentratione-time curve (AUC) for the main metabolite, ginsenoside Rd, were $72.4{\pm}31.6ng/mL$ and $663.9{\pm}285.3{\mu}g{\cdot}h/mL$, respectively. When the ginseng extract (2,000 mg/kg) was orally administered, Cmax and AUC for ginsenoside Rd were $906.5{\pm}330.2ng/mL$ and $11,377.3{\pm}4,470.2{\mu}g{\cdot}h/mL$, respectively. When ginseng extract was orally administered to rats fed NUTRIOSE containing diets (2.5%, 5%, or 10%), Cmax and AUC were increased in the NUTRIOSE receiving groups in a dose-dependent manner. Conclusion: These findings reveal that intestinal microflora promote metabolic conversion of ginsenoside Rb1 and ginseng extract to ginsenoside Rd and promote its absorption into the blood in rats. Its conversion may be induced by prebiotic diets such as NUTRIOSE.

• 한국환경보건학회지
• /
• 제44권6호
• /
• pp.572-580
• /
• 2018

Objectives: Human biomonitoring (HBM) is a measurement of the chemicals and their metabolites in human biological samples and has been successfully employed to determine the exposure levels of environmental chemicals. In this study, we analyzed seasonal variations of the blood or urinary levels of chemicals, and assessed that these differences could affect the results of association study. Methods: The Korea National Environmental Health Survey (KoNEHS) is a nationwide survey that analyzes exposure levels of environmental pollutants, 19 kinds of chemicals including heavy metals and organic chemicals, and the exposure factors in the general population. Based on KoNEHS data, we analyzed the levels of chemicals concentrations over the total survey period (2012-2014) and each season, and assessed the association of thyroid measures with phthalate metabolite and BPA. Results: Exposure levels of blood mercury and lead were lower in summer compare to winter. Bisphenol A and PAHs metabolites were higher in spring and summer, but lower in autumn. VOCs metabolites were generally lower in summer and autumn. Phthalate metabolites were higher in all other seasons than in winter. Pyrethroid metabolite, 3-PBA, was higher in summer and autumn. Regarding seasonal variation of chemical exposures, the statistical significance and size of effects between thyroid measures and phthalate and BPA were changed with season. Conclusion: Seasonal variations of chemical exposure and health outcome should be considered for interpreting biomonitoring results from a public health context.

• 대한의생명과학회지
• /
• 제27권4호
• /
• pp.223-230
• /
• 2021

Tumor necrosis factor alpha (TNF-α) is a principal regulator of inflammation and immunity. The proinflammatory properties of TNF-α can be attributed to its ability to activate the enzyme cytosolic phospholipase A₂ (cPLA₂), which generates potent inflammatory lipid mediators, eicosanoids. L-glutamine (Gln) plays physiologically important roles in various metabolic processes. We have reported that Gln has a potent anti-inflammatory activity via rapid upregulation of mitogen-activated protein kinases (MAPKs) phosphatase (MKP)-1, which preferentially dephosphorylates the key proinflammatory enzymes, p38 MAPK and cytosolic phospholipase A₂ (cPLA₂). In this study, we have investigated whether Gln could inhibit TNF-α-induced cPLA₂ activation. Gln inhibited TNF-α-induced increases in cPLA₂ phosphorylation in the lungs and blood levels of the cPLA₂ metabolites, leukotrine B4 (LTB4) (lipoxygenase metabolite) and prostaglandin E2 (PGE2) (cyclooxygenase metabolite). TNF-α increased p38 and cPLA₂ phosphorylation and blood levels of LTB4 and PGE2, which were blocked by the p38 inhibitor SB202190. Gln inhibited TNF-α-induced p38 and cPLA₂ phosphorylation and production of the cPLA₂ metabolites. Such inhibitory activity of Gln was no longer observed in MKP-1 small interfering RNA-pretreated animals. Our data indicate that Gln inhibited TNF-α-induced cPLA₂ phosphorylation through MKP-1 induction/p38 inhibition, and suggest that the utility of Gln in inflammatory diseases in which TNF-α plays a major role in their pathogenesis.