• BMB Reports
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• 제39권1호
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• pp.91-96
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• 2006

Previously, we have shown that nitric oxide (NO) directly activates the Maxi-K channels. In the present study, we have investigated whether NO has prolonged effects on the Maxi-K channels reconstituted in lipid bilayer. Application of S-nitroso-N-acetyl-D, L-penicillamine (SNAP), a NO donor, induced an immediate increase of open probability (Po) of Maxi-K channel in a dose-dependent manner. When SNAP was removed from the cytosolic solution, the Po did not simply returned to, but irreversibly decreased to a level lower than that of the control Po. At 0.2 mM, (Z)-[N-(3-Ammoniopropyl)-N-(n-propyl)amino] diazen-1-ium-1,2-diolate (PAPA-NO), another NO donor, produced a similar increase of Po and decrease of Po upon washout. The increasing effects of SNAP on Po were not blocked by either 50 U/ml superoxide dismutase (SOD) or 2 mM N-ethylmaleimide (NEM) pre-treatments. However, NEM appears to be ineffective when applied after SNAP. These results suggest that NO can modulate Maxi-K channel via direct interaction and chemical modification, such as S-nitrosylation in the brain.

• 약학회지
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• 제40권5호
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• pp.550-557
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• 1996

One of therapeutics in liver disease (morbus wilson) is D-penicillamin (D-pen: D-3-mercapto-valin). Especially the cross-linking of collagen molecules could be inhibited by D-pe n in extracellular space. In this study we investigated the antifibrotic effects of D-pen in rats that were induced the liver fibrosis by bile duct ligation and scission (BDL/S). Rats were treated for 4 weeks with D-pen after BDL/S operation or sham operation. The balance between fibrogenesis-marker (PNIIIP) and the fibrolysis-maker (PNIVP) were observed in sera by RIA (radioimmunoassay), and the parameter of collagen deposition in liver tissue (hydroxyproline: HYP) was measured by colorimetry. The weight of liver in BDL/S operated group was increased significantly in compared with sham operation group (15.2g${\pm}$1.1, vs 11.9g${\pm}$3.9: p<0.005, p<0.05). The rats group treated by D-pen showed the lower level of PNIIIP (6.7ng/ml${\pm}$1.5, vs 9.5ng/ml${\pm}$2.8) and the higher value of PIVCP (14.0ng/ml${\pm}$1.9, vs 7.9ng/ml${\pm}$1.5) in sera that compared to untreated rats. The content of HYP was decreased by 141% in BDL/S with D-pen treated group than that of it in BDL/S group. No correlation was revealed between collagen parameters in sera and HYP in liver tissue of BDL/S operated and D-pen treated rats. The group treated with D-pen showed the lower value of clinical biochemistry parameters (GOT: glutamate oxalacetate transaminase, Total-Bilirubin) in compared with only BDL/S operated rats, but the value of GPT (glutamate pyruvate transaminase) and Alkaline phosphatase in two BDL/S groups was nearly same. In the histological finding, we observed mild bile duct proliferation, weak inflammation and fibrosis in BDL/S with D-pen treated group, but BDL/S operated group showed the formation of septum (island of hepatocytes), massive bile duct proliferation. This result represents that the BDL/S operation induces liver fibrosis (cirrhosis) in 4 weeks, and D-pen inhibits the synthesis of collagen weakly and stimulates the degradation of collagen in the extracellular space. We conclude that the monitoring of PNIIIP, PIVCP in sera is useful parameter for screening of antifibrotic effect, and D-pen delay the liver fibrosis.

• Archives of Pharmacal Research
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• 제29권12호
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• pp.1074-1079
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• 2006

As part of our research on phytochemicals that exert protective effects against diseases related to reactive nitrogen species, we have evaluated the scavenging activity of the yellow leaves of Ginkgo biloba on $ONOO^{-}$. The methanol extract and ethyl acetate fraction obtained from yellow leaves of G. biloba evidenced a marked scavenging activity on authentic $ONOO^{-}$. Repeated column chromatography of the active ethyl acetate soluble fraction on silica gel, Sephadex LH-20, and RP-18, resulted in the purification of 15 known compounds, including sciadopitysin (1), ginkgolide B (2), bilobalide (3), isoginkgetin (4), kaempferol (5), luteolin (6), protocatechuic acid (7), bilobetin (8), amentoflavone (9), ${\beta}-sitosterol$ glucopyranoside (10), kaempferol 3-O-rhamnopyranoside (11), kaempferol 3-O-glucopyranoside (12), kaempferol $3-O-[{6^{'}-O-p-coumaroyl-{\beta}-D-glucopyranosyl(1{\rightarrow}2)-{\alpha}-L-rhamnopyranoside]$ (13), kaempferol 3-O-rutinoside (14), and 6-hydroxykynurenic acid (15). Among the compounds isolated, flavonoids (5, 6 and 11-14), protocatechuic acid (7), and 6-hydroxykynurenic acid (15) all exhibited marked scavenging activities on authentic $ONOO^{-}$. The $IC_{50}$ values of 5-7, 11-14 and 15 were as follows: $2.86{\pm}0.70,\;2.30{\pm}0.04,\;2.85{\pm}0.10,\;5.60{\pm}0.47,\;4.16{\pm}1.65,\;2.47{\pm}0.15,\;3.02{\pm}0.48,\;and\;6.24{\pm}0.27\;{\mu}M$, respectively. DL-Penicillamine ($IC_{50}=4.98{\pm}0.27\;{\mu}M$) was utilized as a positive control. However, the other compounds (1-4, 8-10) exerted no effects against $ONOO^{-}$.

• Natural Product Sciences
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• 제14권1호
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• pp.1-11
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• 2008

Peroxynitrite ($(ONOO^-)$ is a cytotoxic species formed from nitric oxide and superoxide anion, which are highly implicated in the pathogenesis of oxidative stress-mediated diseases. The aim of this study was to investigate the scavenging effects of Phellinus linteus on authentic $ONOO^-$, and further phytochemical studies are planned that will attempt to identify the active principles. From the active EtOAc fraction, a mixture of fungisterol and 5-dihydroergosterol (1), a mixture of betulin and 1,2-benzenedicarboxylic acid bis (2-methyl heptyl) ester (2), protocatechualdehyde (3), protocatechuic acid (4), cirsiumaldehyde (5), hispidin (6), caffeic acid (7), phelligridin D (8), uracil (9), gallic acid (10), 2,5-dihydroxybenzoic acid (11), ferulic acid (12), 2,3-dihydroxybenzaldehyde (13), arbutin (14), isoferulic acid (15), guanosine (16), and ellagic acid (17) were isolated, and their structures were characterized based on spectroscopic data. All compounds except 3, 6, 7 and 16 were isolated for the first time from P. linteus. Compounds 3, 4, 6-8, 10-15, and 17 showed potent scavenging activity on $ONOO^-$, with $IC_{50}$ values of $2.06\;{\pm}\;0.10$, $3.45\;{\pm}\;0.57$, $0.71\;{\pm}\;0.05$, $2.78\;{\pm}\;0.36$, $5.42\;{\pm}\;0.26$, $1.13\;{\pm}\;0.02$, $1.82\;{\pm}\;0.17$, $0.91\;{\pm}\;0.19$, $1.59\;{\pm}\;0.09$, $1.88\;{\pm}\;0.07$, $1.22\;{\pm}\;0.37$, and $2.01\;{\pm}\;0.02\;{\mu}M$, respectively, as compared to the positive control, DL-penicillamine, with an $IC_{50}$ value of $5.04\;{\pm}\;0.06\;{\mu}M$.

• 대한임상독성학회지
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• 제2권1호
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• pp.20-22
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• 2004

Acute mercury inhalation poisoning is a rare cause of acute peripheral neuropathy. A 44-year-old female inhaled the fume from heating mercury to treat her palmar dermatitis. For 4 days, this procedure was done for 2-3 minutes after each meal. She subsequently complained flu like symptoms, such as headache, toothache, myalgia and arthralgia. She was admitted for 9 days and then symptoms disappeared. About 3 weeks after exposure, both knee pain developed and then she could not walk. To treat mercury intoxication, she was referred to our hospital. At that time, initial laboratory data were within normal limits, but blood and urinary mercury level were 5.6 11$\mu$g/dl, 132.8 $\mu$g/L. After treatment with D-penicillamine for 7 days, blood and urinary mercury level were 3.9 1$\mu$g/dl, 177.3 $\mu$g/L. During the following 1 month, both leg symptoms remained. Nerve conduction studies were performed, both leg sensory nerve amplitude decreased. These findings were suggestive of peripheral polyneuropathy.

• 한국환경보건학회지
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• 제27권3호
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• pp.71-80
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• 2001

Blood and urine mercury level of three workers were monitored during 60~80 days after high exposure to mercury at the silver refining plant. Mercury was used to form silver-mercury amalgam from plating sludge. Workers were exposed to mercury about 70 days at the several processes, such as hand held weaving, vibration table, and heating from the furnace. mercury was analysed by atomic absorption spectroscopy-vapor generation technique. Recovery from the biological sample was 95.51% and pooled standard deviation was 0.033. At the time of study, there was no work at the workplace. So, airborne mercury concentration was measured with area sampling 5 days after the work, ranged from 0.1459 to 1.2351 mg/㎥(Arithmatic mean 0.4711 mg/㎥, Geometric mean 0.3566 mg/㎥) at the inside of the plant, that is far above the ACGIH's TLV(0.025 mg/㎥) and ranged from 0.0073 to 0.0330 mg/㎥ at the outdoor. Blood mercury levels at the beginning of the monitoring were 4~14 times greater than the American Conference of Governmental Industrial Hygienists Biological Exposure Index(ACGIH BEI, 15 ug/L). Blood mercury levels were decreased logarithmically, that is, rapidly at the high level and slowly at the low level but sustained above the level of the ACGIH BEI 60~80 days after the work. Urine mercury levels at the beginning of the monitoring were 8~16 times greater than the ACGIH BEI(35 ug/g creatinine). Urine mercury levels were decreased logarithmically, but correlation between urine level and off-days were lower than those of blood. Decreasing pattern of blood mercury levels were little affected than that of urine levels when the chelating agent, D-penicillamine, was administered. There was correlation between blood mercury level and urine mercury level(0.81~0.83) but it didn\`t mean that the highest blood mercury level corresponded the highest urine mercury level. In our study, Case 1 always shows the highest level in urine but case 3 always shows the highest level in blood. Creatinine correction represented better correlations between urine mercury levels and blood levels, and between urine levels and off-days rather than by urine volume. Spot urine sampling had a wide variation than that of whole day urine sampling. So, We recommend spot urine sampling for screening and whole day urine sampling for exact diagnosis.