Biomedical subjects

K M Ko

Publications and source records attributed to K M Ko.

At least 19 recordsLinked to original sources

PubMed2006

Evaluation of acute tacrine treatment on passive-avoidance response, open-field behavior, and toxicity in 17- and 30-day-old mice.

The potential of tacrine in altering cognitive/behavioral function as well as in causing toxicity was evaluated in mice of 17 and 30 days of age. Cognitive and behavioral studies were performed using a step-through passive avoidance task and a habituation open-field test with a 24-h retention interval. Tacrine was subcutaneously injected (1.25-80 micro mol/kg) 30 min prior to the first session of both tests. During the training session in step-through task, tacrine treatment dose-dependently decreased the number of footshocks, with IC(50) values being 7.8 and 23.3 micro mol/kg in 17- and 30-day-old mice, respectively. Treatment with tacrine at a low dose (5 micro mol/kg) significantly prolonged the retention latency in 17-day-old mice only, but it shortened the retention latency at high doses of 20 and 40 micro mol/kg in 17- and 30-day-old, respectively. During the acquisition session in the open-field test, tacrine treatment dose-dependently decreased the locomotor activity in 17- and 30-day-old mice, with IC(50) values being 15.1 and 24.7 micro mol/kg, respectively. High doses of tacrine invariably increased the locomotor activity during the recall session. Tacrine treatment at a dose of 40 micro mol/kg caused a significant increase in serum alanine aminotransferase activity in 17- and 30-day-old mice at 6 h post-dosing, with the extent of stimulation in 30-day-old mice being more prominent. In conclusion, tacrine was more potent in enhancing/disrupting the cognitive function, inhibiting locomotor activity as well as in causing hepatotoxicity in 17-day-old than in 30-day-old mice.

Animals↗

PubMed2006

Dang-Gui Buxue Tang produces a more potent cardioprotective effect than its component herb extracts and enhances glutathione status in rat heart mitochondria and erythrocytes.

The effects of pretreatment with Dang-Gui Buxue Tang (DBT, a decoction of Astragali and Angelica roots) and its component herb extracts on myocardial ischaemia-reperfusion (IR) injury were examined in rats ex vivo. DBT and its component herb extracts could protect against myocardial IR injury in a dose-dependent manner. The more potent cardioprotection afforded by DBT pretreatment than that of a mixture of Astragali and Angelica root extracts was associated with a much higher extraction yield of active ingredients from Angelica root in the herbal decoction. The high level of active ingredients might increase their bioavailability after oral administration. DBT pretreatment could enhance myocardial mitochondrial as well as red blood cell (RBC) glutathione status, thereby increasing their resistance to oxidative stress-induced injury in rats. The measurement of RBC glutathione status may serve as a useful index for the antioxidant effect produced by DBT treatment in human subjects.

Angelica sinensis↗

PubMed2005

Benign metastasising leiomyoma: a rare but possible cause of bilateral pulmonary nodules in Chinese patients.

We report three cases of benign metastasising leiomyoma, which is a rare cause of multiple lung nodules, in three Hong Kong Chinese females. One patient presented with pleuritic chest pain, another was asymptomatic, while the last presented with haemoptysis. All three patients had previously undergone surgical resection of uterine leiomyomas. Multiple lung nodules mimicking lung metastases were demonstrated on chest radiographs, and all three diagnoses were obtained from lung biopsies. Hormonal therapy was given to two patients with variable responses. To the best of our knowledge, this is the first report of benign metastasising leiomyoma in Hong Kong Chinese population. It highlights the importance of considering this rare and benign disease in premenopausal females presenting with multiple lung nodules.

Adult↗

PubMed2004

Comparing an in vitro electrochemical measurement of superoxide scavenging activity with an in vivo assessment of antioxidant potential in Chinese tonifying herbs.

The in vitro superoxide scavenging activity (as determined by electrochemical measurement) and the in vivo antioxidant potential (as determined by a mouse model of carbon tetrachloride (CCl(4)) hepatotoxicity) of methanolic extracts prepared from 10 Chinese tonifying herbs were compared. Electrochemical measurement using a cytochrome c (Cyt. c) sensor showed that all of the tested herbal extracts exhibited a medium superoxide scavenging activity of different potency, as indicated by their IC(50) values. The in vivo measurement demonstrated that 80% of the herbal extracts displayed in vivo antioxidant potential, as assessed by the percentage of protection of the activity of plasma alanine aminotransferases and the hepatic glutathione regeneration capacity under CCl(4)-intoxicated condition. Although the in vitro antioxidant activity did not correlate quantitatively with the in vivo antioxidant potential, for 8 out of 10 samples a similar tendency was found. The rapid amperometric assessment of antioxidant potential by Cyt. c sensor may offer a convenient and direct method for screening as well as the quality control of herbal products.

Animals↗

PubMed2004

A yang-promoting Chinese herbal suppository preparation enhances the antioxidant status of red cells in male human subjects.

In the 16-week pilot study, the effect of a Yang-promoting Chinese herbal suppository preparation (VI-28) on the red cell antioxidant status was examined in 31 healthy male subjects aged 41-66 years old. VI-28 treatment for 12 weeks (one suppository (0.3 g) daily for week 1-4; one every 2 days for week 5-8; one every 3 days for week 9-12) produced a time/dose-dependent alteration in red cell antioxidant status. The VI-28-induced change is characterized by a slight depletion in cellular reduced glutathione (GSH) level and a decrease in susceptibility to peroxide-induced lipid peroxidation as well as increases in catalase (CAT) and Cu-Zn-superoxide dismutase (SOD) activities. While a reversal trend of change was observed in cellular GSH level, the susceptibility to lipid peroxidation as well as the CAT activity after the cessation of treatment for 4 weeks, the SOD activity exhibited a protracted increase. The results indicate that VI-28 treatment enhances red cell antioxidant status in male subjects. The beneficial effect of VI-28 treatment on red cells may re fl ect a corresponding change in antioxidant status of peripheral tissues.

Adult↗

PubMed2002

Schisandrin B protects against tacrine- and bis(7)-tacrine-induced hepatotoxicity and enhances cognitive function in mice.

Intragastric administration (100-200 micromol/kg) of tacrine (THA) or bis(7)-THA could cause an acute and dose-dependent increase in plasma alanine aminotransferases activity in mice at 6 h after the drug administration. The increase in plasma enzyme activity was associated with an increase in hepatic malondialdehyde level, an indirect index of oxidative tissue damage. Pretreating mice with schisandrin B (Sch B), an active dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, at a daily dose of 0.125-0.5 mmol/kg for 3 days protected against the THA/bis(7)-THA induced hepatic oxidative damage in a dose-dependent manner. Sch B treatment (0.025-0.5 mmol/kg/day x 5) also enhanced the passive avoidance-response in mice as assessed by the step-through task experiment. The ensemble of results suggests that Sch B may be useful for reducing the potential hepatotoxicity of THA/bis(7)-THA in anti-Alzheimer's therapy.

Alanine Transaminase↗

PubMed2002

In vivo antioxidant action of a lignan-enriched extract of Schisandra fruit and an anthraquinone-containing extract of Polygonum root in comparison with schisandrin B and emodin.

The in vivo antioxidant action of a lignan-enriched extract of the fruit of Schisandra chinensis (FS) and an anthraquinone-containing extract of the root of Polygonum multiflorum (PME) was compared with their respective active constituents schisandrin B (Sch B) and emodin by examining their effect on hepatic mitochondrial glutathione antioxidant status in control and carbon tetrachloride (CCl 4 )-intoxicated mice. FS and PME pretreatments produced a dose-dependent protection against CCl 4 hepatotoxicity, with the effect of FS being more potent. Pretreatment with Sch B, emodin or alpha-tocopherol (alpha-Toc) also protected against CCl 4 hepatotoxicity, with the effect of Sch B being more potent. The extent of hepatoprotection afforded by FS/Sch B and PME/emodin pretreatment against CCl 4 toxicity was found to correlate well with the degree of enhancement in hepatic mitochondrial glutathione antioxidant status, as evidenced by increases in reduced glutathione level and activities of glutathione reductase, glutathione peroxidase as well as glutathione S-transferases, in both control and CCl 4 -intoxicated mice. alpha-Toc, which did not enhance mitochondrial glutathione antioxidant status, seemed to be less potent in protecting against CCl 4 hepatotoxicity. The ensemble of results indicates that FS/PME produced a more potent in vivo antioxidant action than alpha-Toc by virtue of their ability to enhance hepatic mitochondrial glutathione antioxidant status and that the differential potency of FS and PME can be attributed to the difference in in vivo antioxidant potential between Sch B and emodin. Abbreviations. ALT:alanine aminotransferases CCl 4 :carbon tetrachloride FS:lignan-enriched extract of Schisandra fruit GRD:glutathione reductase GSH:reduced glutathione GSH-Px: Se-glutathione peroxidase GST:glutathione S-transferases mt:mitochondrial MDA:malondialdehyde PME:anthraquinone-containing fraction of Polygonum root Sch B:schisandrin B SDH:sorbitol dehydrogenase alpha-Toc:alpha-tocopherol

Alanine Transaminase↗

PubMed2001

Hepatoprotective action of an oleanolic acid-enriched extract of Ligustrum lucidum fruits is mediated through an enhancement on hepatic glutathione regeneration capacity in mice.

The fruits of Ligustrum lucidum Ait. (FLL) were fractionated into petroleum ether (FLL-Pe), chloroform (FLL-Ch), butanol (FLL-Bu) and aqueous (FLL-Aq) fractions, of which FLL-Ch and FLL-Bu were found to be enriched with oleanolic acid (OLA). The in vivo antioxidant activities of various FLL fractions and OLA were assessed by examining the effect on carbon tetrachloride (CCl(4))-induced hepatotoxicity in mice. Pretreatment of animals with various FLL fractions could protect against CCl(4)-induced hepatotoxicity to a varying degree, with OLA-enriched FLL-Bu and FLL-Ch being more potent. However, a mortality rate of 60% was observed in the FLL-Ch pretreated and CCl(4)-intoxicated mice. OLA pretreatment also produced a dose-dependent protection against CCl(4) hepatotoxicity. The hepatoprotection afforded by FLL-Bu or OLA pretreatment was associated with an enhancement of hepatic-glutathione regeneration capacity (GRC). In contrast, the inability of FLL-Aq pretreatment to enhance hepatic GRC resulted in a failure to prevent CCl(4)-induced hepatic injury. The results suggest that the hepatoprotective action afforded by OLA-enriched FLL-Bu or OLA pretreatment may be mainly mediated by the enhancement of hepatic GRC, particularly under conditions of CCl(4)-induced oxidative stress.

Animals↗

PubMed2001

Schisandrin B modulates the ischemia-reperfusion induced changes in non-enzymatic antioxidant levels in isolated-perfused rat hearts.

Isolated Langendorff-perfused rat hearts were subjected to a fixed period of ischemia followed by increasing periods of reperfusion for investigating the changes in the extent of ischemia-reperfusion (IR) injury and tissue levels of non-enzymatic antioxidants. Effects of schisandrin B (Sch B) and (+/-) alpha-lipoic acid (LA) pretreatment were also examined. A 40-min of ischemia (40-I) followed by 20- or 40-min of reperfusion (20-R or 40-R) caused sustainable tissue damage in isolated hearts, as indicated by the increased extent of lactate dehydrogenase (LDH) leakage and impaired contractile force. The myocardial IR injury was associated with a marked decrease in tissue ascorbic acid (V(C)) level. However, myocardial reduced glutathione (GSH) and alpha-tocopherol (V(E)) levels remained relatively unchanged except under a more severe IR condition (40-I, 40-R). Pretreating rats with Sch B or LA at a daily dose of 1.2 mmol/kg for 3 days protected against IR injury in isolated hearts to varying degrees. While only Sch B pretreatment could improve the recovery of contractile force, LA pretreatment produced a better inhibitory effect on LDH leakage. The protection against IR injury was associated with significant increases in myocardial V(E) and V(C) levels in both Sch B and LA pretreated hearts. The ensemble of results suggests that the cardioprotection afforded by Sch B or LA pretreatment may at least in part be attributed to the modulation on the interplay among non-enzymatic antioxidants under oxidative stress induced by IR.

Animals↗

PubMed2001

Altered susceptibility to ischemia-reperfusion injury in isolated-perfused hearts of short-term diabetic rats associated with changes in non-enzymatic antioxidants.

The effects of short-term (2-week) diabetes on myocardial ischemia-reperfusion (I-R) injury and associated changes in myocardial non-enzymatic antioxidant level were examined. Isolated-perfused hearts prepared from control and diabetic rats were subjected to increasing periods of ischemia and reperfusion, and myocardial I-R injury was assessed by measuring the extent of lactate dehydrogenase (LDH) leakage and contractile force recovery. While a brief period (20 min) of post-ischemic reperfusion caused a smaller extent of LDH leakage, the prolonged period (40 min) of reperfusion produced a greater degree of I-R injury in diabetic hearts, as indicated by the impaired recovery of contractile force. The apparent protection against I-R injury in diabetic hearts during the early phase of post-ischemic reperfusion was associated with increases in myocardial reduced glutathione/ascorbic acid and a-tocopherol levels, with the effect on a-tocopherol being most prominent. Insulin treatment could reverse the diabetes-associated changes in susceptibility to myocardial I-R injury and antioxidant response. The ensemble of results indicates that the myocardium isolated from short-term diabetic rat can produce a beneficial antioxidant response to I-R challenge, which may, in turn, be attributable to the decreased susceptibility to I-R injury observable during the early phase of reperfusion.

Animals↗

PubMed2001

Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced apoptosis and Hsp70 expression in mouse liver.

Tumor necrosis factor-alpha (TNFalpha) could cause apoptosis in hepatic tissue of D-galactosamine sensitized mice, as evidenced by the increase in the extent of DNA fragmentation. The hepatic apoptosis induced by TNFalpha was associated with hepatocellular damage as assessed by plasma alanine aminotransferase activity. Schisandrin B (Sch B) pretreatment at daily doses ranging from 0.5 to 2 mmol/kg for 3 days caused a dose-dependent protection against TNFalpha-induced apoptosis in mice. The hepatoprotection was accompanied by a parallel reduction in the extent of hepatocellular damage. The same Sch B pretreatment regimens increased hepatic Hsp70 level in a dose-dependent manner. The relevance of Sch B-induced increase in Hsp70 expression to the prevention of TNFalpha-triggered hepatic apoptosis remains to be elucidated.

Animals↗

PubMed2000

Myocardial protection against ischaemia-reperfusion injury by a Polygonum multiflorum extract supplemented 'Dang-Gui decoction for enriching blood', a compound formulation, ex vivo.

'Dang-Gui Decoction for Enriching the Blood' (BE), a traditional Chinese formulation comprising Angelica sinensis and Astragalus membranaceus, is used for stimulating red blood cell production as well as enhancing cardiovascular function. In the present study, we have demonstrated the myocardial protection afforded by BE pretreatment against ischaemia-reperfusion (IR) injury in isolated-perfused rat hearts. A more complete and potent myocardial protection against IR injury was also shown by a Polygonum multiflorum extract supplemented BE preparation (BEA). The results suggest that the more potent cardioprotective action of BEA may be related to its ability to sustain the myocardial glutathione antioxidant status under conditions of IR-induced oxidative stress, which may possibly in turn result from the synergistic interaction between the BE and Polygonum extract.

Angelica sinensis↗

PubMed2000

Modulation of Nad(P)H:quinone oxidoreductase (NQO1) activity mediated by 5-arylamino-2-methyl-4,7-dioxobenzothiazoles and their cytotoxic potential.

Synthesized 5-arylamino-2-methyl-4,7-dioxobenzothiazoles 3a-3o were evaluated for modulation of NAD(P)H: quinone oxidoreductase (NQO1) activity with the cytosolic fractions derived from cultured human lung cancer cells and their cytotoxicity in cultured several human solid cancer cell lines. The 4,7-dioxobenzothiazoles affected the reduction potential by NQO1 activity and showed a potent cytotoxic activity against human cancer cell lines. The tested compounds 3a, 3b, 3g, 3h, 3n and 3o were considered as more potent cytotoxic agents, and comparable modulators of NQO1 activity.

Antineoplastic Agents↗

PubMed2000

Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT-diaphorase activity.

Pretreating mice with schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, at a daily dose of 1 mmol/kg for 3 days protected against menadione-induced hepatic oxidative damage in mice, as evidenced by decreases in plasma alanine aminotransferase activity (78%) and hepatic malondialdehyde level (70%), when compared with the menadione intoxicated control. In order to define the biochemical mechanism involved in the hepatoprotection afforded by Sch B pretreatment, we examined the activity of DT-diaphorase (DTD) in hepatocytes isolated from Sch B pretreated rats. Hepatocytes isolated from Sch B pretreated (a daily dose of 1 mmol/kg for 3 days) rats showed a significant increase (25%) in DTD activity. The increase in DTD activity was associated with the enhanced rate of menadione elimination in the hepatocyte culture. The ensemble of results suggests that the ability of Sch B pretreatment to enhance hepatocellular DTD activity may at least in part be attributed to the protection against menadione hepatotoxicity.

Alanine Transaminase↗

PubMed2000

Differential effect of schisandrin B and dimethyl diphenyl bicarboxylate (DDB) on hepatic mitochondrial glutathione redox status in carbon tetrachloride intoxicated mice.

The effects of schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, and dimethyl diphenyl bicarboxylate (DDB), a synthetic intermediate of schisandrin C (also a dibenzocyclooctadiene derivative), on hepatic mitochondrial glutathione redox status in control and carbon tetrachloride (CCl4)-intoxicated mice were examined. Treating mice with Sch B or DDB at a daily oral dose of 1 mmol/kg for 3 d did not produce any significant alterations in plasma alanine aminotransferase (ALT) and sorbital dehydrogenase (SDH) activities. CCl4 treatment caused drastic increases in both plasma ALT and SDH activities in mice. Pretreating mice with Sch B or DDB at the same dosage regimen significantly suppressed the CCl4-induced increase in plasma ALT activity, with the inhibitory effect of Sch B being much more potent. Sch B, but not DDB, pretreatment could also decrease the plasma SDH activity in CCl4-intoxicated mice. The lowering of plasma SDH activity, indicative of hepatoprotection against CCl4 toxicity, by Sch B pretreatment was associated with an enhancement in hepatic mitochondrial glutathione redox status as well as an increase in mitochondrial glutathione reductase (mtGRD) activity in both non-CCl4 and CCl4-treated mice. DDB pretreatment, though enhancing both hepatic mitochondrial glutathione redox status and mtGRD activity in control animals, did not produce any beneficial effect in CCl4-treated mice. The difference in hepatoprotective action against CCl4 toxicity between Sch B and DDB may therefore be related to their ability to maintain hepatic mitochondrial glutathione redox status under oxidative stress condition.

Alanine Transaminase↗

PubMed1999

Methylenedioxy group and cyclooctadiene ring as structural determinants of schisandrin in protecting against myocardial ischemia-reperfusion injury in rats.

As a preliminary investigation to exploring whether the methylenedioxy group and the cyclooctadiene ring of the dibenzo[a,c]cyclooctadiene (schisandrin) molecule plays an important role in the protection against myocardial ischemia-reperfusion (IR) injury, we examined the effects of three schisandrins, namely schisandrin A (Sch A), schisandrin B (Sch B), and schisandrin C (Sch C), and the effect of dimethyl-4,-4'-dimethoxy-5,6,5',6'-dimethylene-dioxy-biphenyl-2,2' -bicarboxylate (DDB), an intermediate compound derived from the synthesis of Sch C, on myocardial IR injury in isolated Langendorff-perfused rat hearts. While pretreating rats with Sch A or DDB at a daily oral dose of 1.2 mmol/kg for 3 days did not protect the isolated-perfused hearts against IR-induced damage, pretreatment with Sch B or Sch C at the same dosage regimen produced cardioprotective action. The extent of cardioprotection afforded by Sch B or Sch C pretreatment correlated well with the degree of enhancement in myocardial glutathione antioxidant status, as indicated by significant increases in the tissue-reduced glutathione level and Se-glutathione peroxidase (EC 1.11.1.9), glutathione transferases (EC 2.5.1.18), and glutathione reductase (EC 1.6.4.2) activities in ischemic-reperfused hearts when compared with the unpretreated IR control. Our results indicate that both the methylenedioxy group and the cyclooctadiene ring of the schisandrin molecule are important structural determinants in mediating the protection against myocardial IR injury.

Animals↗

PubMed1999

Schisandrin B protects against myocardial ischemia-reperfusion injury by enhancing myocardial glutathione antioxidant status.

The effects of Schisandrin B (Sch B) and dimethyl-4,4'-dimethoxy-5,6,5',6'dimethylene-dioxy-biphenyl-2,2'-+ ++bicarboxylate (DDB) treatment on myocardial ischemia-reperfusion (IR) injury in isolated perfused rat hearts were examined under both in vitro and ex vivo conditions. In vitro administration of liposome-entrapped Sch B or DDB during reperfusion did not protect against myocardial IR injury, whereas ascorbic acid or Trolox supplemented perfusate produced protective effect, as evidenced by the significant decrease in the extent of lactate dehydrogenase leakage as well as an improvement in contractile force recovery. Myocardial protection afforded by N-acetyl-L-cysteine supplemented perfusate was not accompanied by the enhancement in contractile force recovery. In ex vivo experiment, pretreatment of Sch B (0.6/1.2 mmol/kg/day x 3) protected against IR-induced myocardial damage in a dose-dependent manner. The myocardial protection was associated with an enhancement in myocardial glutathione antioxidant status, as indicated by significant reductions in both the extent of IR-induced reduced glutathione depletion and inhibition of Se-glutathione peroxidase and glutathione reductase activities. In contrast, the inability of DDB pretreatment to enhance myocardial glutathione antioxidant status resulted in a failure in preventing IR injury. The ensemble of results suggests that the myocardial protection afforded by Sch B pretreatment, which was unlikely due to free radical scavenging action, may be mainly mediated by the enhancement of myocardial glutathione antioxidant status, particularly under oxidative stress conditions.

Animals↗

PubMed1998

Myocardial protective effect of an anthraquinone-containing extract of Polygonum multiflorum ex vivo.

An ethyl acetate extract of Polygonum multiflorum Thunb. (PME) was fractionated into an anthraquinone-containing (PME-I) and a non-anthraquinone-containing (PME-II) fraction. The effects of PME and its related extracts pretreatment on myocardial ischemia-reperfusion (IR) injury in isolated perfused rat hearts were examined. Pretreatment with PME extract or its anthraquinone-containing fraction produced a dose-dependent protection against myocardial IR injury, as evidenced by a significant decrease in the extent of LDH leakage as well as an improvement in contractile force recovery. The myocardial protection was found to be associated with an enhancement in myocardial glutathione antioxidant status, as indicated by significant reductions in both the extent of IR-induced reduced glutathione (GSH) depletion and inhibition of Se-glutathione peroxidase (GPX) and glutathione reductase (GRD) activities. Both alpha-tocopherol acetate (VE) and emodin (EMD) pretreatments protected against IR-induced myocardial injury as assessed by the decrease in the extent of LDH leakage. But the contractile force recovery of the ischemic-reperfused hearts prepared from VE or EMD pretreated animals was not improved. The more complete myocardial protection afforded by the anthraquinone-containing fraction of PME extract may be related to its ability to sustain the glutathione antioxidant status under the condition of IR-induced oxidative stress.

Animals↗