• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.65-71
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• 2008

The present study examined the inhibitory effect of licorice compounds glycyrrhizin and a metabolite $18{\beta}$-glycyrrhetinic acid on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and on the 1-methyl-4-phenylpyridinium ($MPP^+$)-induced cell death in differentiated PC12 cells. MPTP treatment increased the activities of total superoxide dismutase, catalase and glutathione peroxidase and the levels of malondialdehyde and carbonyls in the brain compared to control mouse brain. Co-administration of glycyrrhizin (16.8 mg/kg) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. In vitro assay, licorice compounds attenuated the $MPP^+$-induced cell death and caspase-3 activation in PC12 cells. Glycyrrhizin up to $100{\mu}M$ significantly attenuated the toxicity of $MPP^+$. Meanwhile, $18{\beta}$-glycyrrhetinic acid showed a maximum inhibitory effect at $10{\mu}M$; beyond this concentration the inhibitory effect declined. Glycyrrhizin and $18{\beta}$-glycyrrhetinic acid attenuated the hydrogen peroxide- or nitrogen species-induced cell death. Results from this study indicate that glycyrrhizin may attenuate brain tissue damage in mice treated with MPTP through inhibitory effect on oxidative tissue damage. Glycyrrhizin and $18{\beta}$-glycyrrhetinic acid may reduce the $MPP^+$ toxicity in PC12 cells by suppressing caspase-3 activation. The effect seems to be ascribed to the antioxidant effect.

• Biomolecules & Therapeutics
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• v.7 no.2
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• pp.112-120
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• 1999

The protective actions of ambroxol, rutin, glutathione and harmaline on oxidative damages of various tissue components were compared. The mechanisms by which they prevent oxidative tissue damages were explored. Lipid peroxidation of liver microsomes induced by combinations of $Fe^{2+}$ and ascorbate or $Fe^{+3}$, ADP and NADPH was inhibited by $50\; \muM$ of rutin, ambroxol, harmaline and glutathione. Ambroxol ($100\; \muM$) inhibited the degradation of hyaluronic acid by $Fe^{2+}$, $H_2O$_2$ and ascorbate, and it was greater than that of harmaline, whereas hyaluronic acid degradation was not prevented by rutin and glutathione. The compounds used ($100\; \muM$) did not protect the degradation of cartilage collagen by xanthine and xanthine oxidase. Rutin, glutathione and harmaline decreased the degradation of IgG by xanthine and xanthine oxidate, while ambroxol did not attenuate degradation of IgG. Glutathione showed a scavenging action on $H_2O_2$. The compounds all showed scavenging actions on hydroxyl radical. Ambroxol and harmaline exhibited quenching effects en singlet oxygen. In conclusion, ambroxol, rutin, glutathione and harmaline may exert protective effects differently on tissue components against oxidative attack depend on kind of tissue component and free radical.

• Journal of Nutrition and Health
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• v.34 no.5
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• pp.513-524
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• 2001

This study was performed to investigate the effects of dry powders, ethanol extracts and juices of radish and onion on lipid metabolism, lipid peroxidation and antioxidative enzyme activity in rats. Forty-nine male Sprague-Dawley rats weighing 157$\pm$6g were blocked into seven groups according to body weight and raised for four weeks with diets containing 5%(w/w) dry powders of two different vegetables consumed frequently by Korean-radish(Raphanus sativus L.) and onion(Allium cepa L.), ethanol extracts and juices from equal amount of each dry powder. All the powders, ethanol extracts and juices of radish and onion decreased total lipids, triglycerides and total cholesterol concentrations in plasma and liver. Above all, onion ethanol extract decreased them most remarkably. It was thought that organosulfur compounds and flavonoids extracted from onion by ethanol inhibited biosynthesis and absorption of lipid and promoted degradation of lipid. Radish powder also decreased them by increasing fecal excretions of total lipids, triglycerides and total cholesterol most effectively. Catalase and glutathine peroxidase(GSH-px) activities in red blood cell(RBC) were most remarkably increased by radish powder and onion powder respectively. Superoxide dismutase(SOD), catalase and GSH-px activities in liver were most remarkably increased by onion ethanol extract, radish powder and onion ethanol extract respectively. Xanthine oxidase(XOD) activities in liver were most effectively decreased by ethanol extracts of radish and onion. Thiobarbituric acid reactive substance (TBARS) levels in plasma and liver of experimental groups were significantly lower than those of controls. Above all, onion powder decreased them most effectively. It was thought that vitamin E and high flavonoids in onion powder inhibited lipid peroxidation, promoting liver and RBC SOD, catalase and GSH-px activities and inhibiting XOD activities effectively. Flavonoids in onion ethanol extract inhibited lipid peroxidation, promoting three antioxident enzyme activities and inhibiting XOD activities most remarkably. Also flavonoids and high vitamin C in radish powder inhibited lipid peroxidation, promoting liver and RBC catalase most remarkably and inhibiting XOD activities. In conclusion, radish and onion were effective in lowering lipid levels and inhibiting of lipid peroxidation in animal tissue. From these data, radish and onion can be recommended in the treatment and prevention of diseases such as cardiovascular disease and cancer and in delaying aging. As ethanol from onion were most effective in lowering lipid level and promoting three antioxident enzymes, and inhibited lipid peroxidation as did we should try to utilize onion skin which is discarded though reported to have abundant flavonoids. (Korean J Nutrition 34(5) : 513~524, 2001)

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.1
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• pp.19-25
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• 2002

The objectives of this study were to understand the possible mechanism of duck sperm toxicity induced by arsenic exposure in vivo, and to investigate the roles of the antioxidant L-ascorbic acid in ameliorating the arsenic-induced sperm impairment. To test the acute toxicity, the percentages of mortality of mature drakes treated with different concentrations of trivalent sodium arsenite, As (III), and pentavalent sodium arsenate, As (V) were measured. The LD50 value of As (III) for mature drakes was $4.89{\pm}1.49$ ppm. Although As (V) didn't cause any deaths even at a concentration of 40 ppm, the chronic toxicity of As (V) on sperm quality was shown by a decreased fertilization rate. When the concentrations of As (V) were above 0.4 ppm, fertilization rates were lower than those of 0.04 ppm and control. Drakes treated with 40 ppm of As (V) had the highest malondialdehyde (MDA) level in the testis tissue, $3.100{\pm}0.218{\mu}mole/g$ testis. This showed that 40 ppm of As (V) significantly induced lipid peroxidation in testis tissue. For the 1.2 ppm As (III) treatment, several significant effects were observed: (1) sperm motility was decreased most dramatically by $52.0{\pm}9.1$% after three days of incubation; (2) fertilization rate of artificially inseminated semen was the lowest, $26.4{\pm}15.4$; (3) the MDA concentration in testis tissue, $7.846{\pm}0.246{\mu}mole/g$ testis, was significantly higher than the others (p<0.05); (4) the sperm number, $1.17{\pm}0.40({\times}10^9)$, was significantly lower than with the 60 ppb and control treatments (p<0.05); (5) a black appearance and soft texture was observed in the testis tissue. The antioxidant L-ascorbic acid administered along with 1.2 ppm As (III) decreased the toxicity of arsenic. The ameliorating effects included: improved sperm motility, increased sperm number and fertilization rate, and decreased MDA concentration in the testis tissue. This study suggests that the toxicity of the trivalent arsenic on sperm quality is partly from free radicals generated by its metabolic pathway, and the antioxidant ascorbic acid ameliorates arsenic-caused sperm impairment.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.97-97
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• 2003

This study is investigated the effect of Rubus coreanus MIQ. against nephrotoxicity induced by cisplatin in rat. We examined the potency of the extract of R. coreanus fruits by the activity-guided fractionation. The EtOAc- and BuOH fraction, niga-ichigoside F$_1$and 23-hydroxytormentic acid showed significant protective effects as lipid peroxidation in renal tissue and was was not affect the activity of xanthine oxidase and aldehyde oxidase by cisplatin-induced nephrotoxicity. The concentration of glutathione in renal tissue was decreased by cisplatin-induced nephrotoxicity, but was improved by pretreatment of R. coreanus compounds especially in butanol, ethylacetate fraction and 23-hydroxytormentic acid.

• Biomedical Science Letters
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• v.14 no.1
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• pp.13-18
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• 2008

Excessive alcohol consumption is associated with increased risks of many diseases including cancer. Individuals who regularly consume excessive quantities of alcohol have a greater risk of developing head and neck cancers such as esophageal, pharyngeal and oral cavity cancers if they are deficient in ALDH2 expression compared to normal populations. We evaluated lipid peroxidation in Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. Malondialdehyde(MDA) level in liver tissue was evaluated as a biomarker of oxidative lipid peroxidation. Although the ethanol treatment did not increase the hepatic MDA level both in Aldh2 +/+ mice and in Aldh2 -/- mice, the MDA level was significant higher in the Aldh2 -/- mice than in the Aldh2 +/+ group. The MDA level was also significantly correlated with olive tail moment in blood and the level of 8-OHdG in liver tissue. This is a strong evidence to support our hypothesis that oxidative stress is more intense in Aldh2 -/- mice than in Aldh2 +/+ mice. Our results suggest that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated liver disease, including cancer.

• Toxicological Research
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• v.34 no.2
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• pp.143-150
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• 2018

It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no in vivo data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (${\alpha}_1$) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal ${\alpha}_1-Na$, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of ${\alpha}_1-Na$, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These in vivo findings demonstrate that vanadate might suppress renal ${\alpha}_1-Na$, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.

• Nutrition Research and Practice
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• v.3 no.2
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• pp.114-121
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• 2009

The effect of diet supplemented with red beet (Beta vulgaris L.) leaf on antioxidant status of plasma and tissue was investigated in C57BL/6J mice. The mice were randomly divided into two groups after one-week acclimation, and fed a high fat (20%) and high cholesterol (1%) diet without (control group) or with 8% freeze-dried red beet leaf (RBL group) for 4 weeks. In RBL mice, lipid peroxidation determined as 2-thiobarbituric acid-reactive substances (TBARS value) was significantly reduced in the plasma and selected organs (liver, heart, and kidney). Levels of antioxidants (glutathione and $\beta$-carotene) and the activities of antioxidant enzyme (glutathione peroxidase) in plasma and liver were considerably increased, suggesting that antioxidant defenses were improved by RBL diet. Comet parameters such as tail DNA (%), tail extent moment, olive tail moment and tail length were significantly reduced by 25.1%, 49.4%, 35.4%, and 23.7%, respectively, in plasma lymphocyte DNA of RBL mice compared with control mice, and indicated the increased resistance of lymphocyte DNA to oxidative damage. In addition, the RBL diet controlled body weight together with a significant reduction of fat pad (retroperitoneal, epididymal, inguinal fat, and total fat). Therefore, the present study suggested that the supplementation of 8% red beet leaf in high fat high cholesterol diet could prevent lipid peroxidation and improve antioxidant defense system in the plasma and tissue of C57BL/6J mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.658-665
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• 2007

Phyllostachys pubescens (Maengiong-Juk), a kind of the bamboo, was reported to have many beneficial pharmacological actions. in this study, of using 70% ethanol extract of Phyllostachys pubescens we investigated its efficacy on angiotensin converting enzyme (ACE) and antioxidant enzyme activities. In addition, vasorelaxant effect was examined in rat aortic rings. The inhibitory effect of ACE activity by Phyllostachys pubescens extract (PPE) was dose-dependently increased by 61.42% at 10mg/ml. PPE relaxed the pre-contracted rat aortic rings with 10$^{-6}$M phenylephrine, showing about 88% at 4.0mg/ml. Sprague Dawley (SD) rats were given different concentrations of PPE mixed in the drinking water for 10 weeks. PPE did not show any difference with control group in blood pressure, body weight (BW) and food intake. However, it revealed the highest total antioxidative effect at dose of 1.0 g/100 g BW in plasma by TEAC assay. Thiobarbituric acid reactive substance (TBARS) and protein carbonyl levels which are markers of tissue peroxidation, were significantly lowed at the same dosage. Furthermore, hepatic antioxidant enzymes such as total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and catalase activities were also significantly increased by PPE (1.0 g/100 g BW). In conclusion, we suggest that PPE might have antihypertensive effect through increasing antioxidant activities.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.119-124
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• 2000

We hypothesized that the extent of hypoxic injury would be involved in reduction of oxygen delivery to the tissue. Livers isolated from 18 hr-fasted rats were subjected to $N_2$-induced hypoxia or low flow hypoxia. Livers were perfused with nitrogen/carbon dioxide gas for 45min or perfused with normoxic Krebs-Henseleit bicarbonate buffer (KHBB) at low flow rates around 1 ml/g liver/min far 45min, which caused cells to become hypoxic because of insufficient delivery of oxygen. When normal flow rates(4 ml/g liver/min) of KHBB (pH 7.4, 37$^{\circ}C$, oxygen/carbon dioxide gas) were restored for 30min reoxygenation injury occurred. Lactate dehydrogenase release gradually increased in $N_2$-induced hypoxia, whereas it rapidly increased in low flow hypoxia. Total glutathione in liver tissue was not changed but oxidized glutathione markedly increased after hypoxia and reoxygenation, expecially in $N_2$-induced hypoxia. Similarly, lipid peroxidation in liver tissue significantly increased after hypoxia and reoxygenation in low flow hypoxia. Hepatic drug metabolizing functions (phase I, II) were suppressed during hypoxia, especially in $N_2$-induced hypoxia but improved by reoxygenation in both models. Our findings suggest that hypoxia results in abnormalities in drug metabolizing function caused by oxidative stress and that this injury is dependent on hypoxic conditions.