• Biomolecules & Therapeutics
• /
• v.28 no.1
• /
• pp.25-33
• /
• 2020

Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H₂O₂), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptor-mediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
• /
• 2002.05a
• /
• pp.138-138
• /
• 2002

Oxidative stress has been associated with a number of diseases in human. Among the sources that can generate oxidative stress, it has been reported that iron can generate reactive oxygen species (ROS)with thiol. In iron overload state, increased thiol levels in plasma appeared to be associated with human mortality. In this study we examined whether iron could interact with thiols in plasma, generating ROS. In human plasma, unlike with Fe(III), Fe(II) increased lucigenin-enhanced chemiluminescence in concentration-dependent manner, and this was inhibited by SOD. Boiling of plasma did not affect chemiluminescence induced by Fe(II). Hovever, thiol depletion in plasma by pretreatment with N-ethylmaleimide (NEM)decreased Fe(II)-induced chemiluminescence significantly, suggesting that Fe(II) generated superoxide anion by the nonenzymatic reaction with plasma thiol. Consistent with this findings, albumin, the major thiol contributor in plasma, also generated ROS with Fe(II) and this generation was inhibited by pretreatment with NEM. Treatment with Fe(II) to plasma resulted un significant reduction of oxygen radical absorbance capacity (ORAC) value, suggest that total antioxidant capacity could diminished in iron overload state. In conclusion, In iron overload state, plasma may be affected by oxidative stress mediated by nonenzymatic reaction of Fe (II)with plasma thiol.

• Journal of Life Science
• /
• v.18 no.2
• /
• pp.220-227
• /
• 2008

To clarify the antioxidation effect of the various solvent fractionation of Tetragonia tetragoniodes which has been known to superior plants for the traditional prevention and treatment of stomach-related diseases, total polyphenol and flavonoid contents, vitamin E content, the elimination activity of a DPPH free radical and superoxide anion, inhibition activity of the superoxide generation, reducing power and metal chelating effects were estimated. The contents of the polyphenol compounds were highest in the DCM and EA fractionation, and the content of flavonoid was high in the order of HX and EA fractionation. The vitamin E content showed high in the order of the HX and DCM fractionation among solvent fractions. $IC_{50}$ for the elimination effect of a DPPH radical were estimated as 554.25 and $394.96{\mu}g/ml$ in the DCM and EA fractions, respectively. These values were higher than that of BHT $784.7{\mu}g/ml$ widely used in antioxidation effect. The inhibition activity of the superoxide generation using the T. tetragoniodes solvent fractions represented the effects similar to that of ${\alpha}$-tocopherol known to prevent the lipoprotein oxidation, but lower consequences than that of the phenol-resins, BHT and BHA, respectively. In the antioxidation activity derived by the reducing capability, the EA fractionation in a 1.5 mg/ml concentration showed higher than that of ${\alpha}$-tocopherol.

• The Korean Journal of Pharmacology
• /
• v.32 no.2
• /
• pp.201-209
• /
• 1996

Restoration of the blood flow after a period of ischemia is accompanied by generation of toxic oxygen radicals. This phenomenon may account for the occurrence of reperfusion-mediated tissue injury in ischemic hearts. In in vitro studies, although oxygen radicals can be generated from a variety of sources, including xanthine oxidase system, activated leucocytes, mitochondria and others, the most important source and mechanism of oxygen radical production in the post-ischemic reperfused hearts is unclear. In the present study, we tested the hypothesis that the respiratory chain of mitochondria might be an important source of oxygen radicals which are responsible for the development of the reperfusion injury of ischemic hearts. Langendorff-perfused, isolated rat hearts were subjected to 30 min of global ischemia at $37^{\circ}C$, followed by reperfusion. Amytal, a reversible inhibitor of mitochondrial respiration, was employed to assess the mitochondrial contributions to the development of the reperfusion injury. Intact mitochonria were isolated from the control and the post-ischemic reperfused hearts. Mitochondrial oxygen radical generation was measured by chemiluminescence method and the oxidative tissue damage was estimated by measuring a lipid peroxidation product, malondialdehyde(MDA). To evaluate the extent of the reperfusion injury, post-ischemic functional recovery and lactate dehydrogenase(LDH) release were assessed and compared in Amytal-treated and -untreated hearts. Upon reperfusion of the ischemic hearts, MDA release into the coronary effluent was markedly increased. MDA content of mitochondria isolated from the post-ischemic reperfused hearts was increased to 152% of preischemic value, whereas minimal change was observed in extramitochondrial fraction. The generation of superoxide anion was increased about twice in mitochondria from the reperfused hearts than in those from the control hearts. Amytal inhibited the mitochondrial superoxide generation significantly and also suppressed MDA production in the reperfused hearts. Additionally, Amytal prevented the contractile dysfunction and the increased release of LDH observed in the reperfused hearts. In conclusion, these results indicate that the respiratory chain of mitochondria may be an important source of oxygen radical formation in post-ischemic reperfused hearts, and that oxygen radicals originating from the mitochondria may contribute to the development of myocardial reperfusion injury.

• Korean Journal of Food Science and Technology
• /
• v.33 no.3
• /
• pp.378-383
• /
• 2001

Formation of superoxide anion $O_2\bar{{\bullet}}$ in the autoxidation of L-ascorbic acid (AsA) in the presence of heavy metal ions were determined. The generation of $O_2\bar{{\bullet}}$ was studied by using superoxide dismutase (SOD) in aqueous and buffer solution, and using nitro bule tetrazolium (NBT) in methanol solution. The remaining amount of AsA was significantly higher in the presence of SOD than in its absence. It suggested that SOD stabilizes AsA in aqueous and buffer solution because of scavenging $O_2\bar{{\bullet}}$ formed during the autoxidation reaction of AsA in the presence of heavy metal ions. NBT has an absorption maximum at about 560 nm in methanol solution. The absorbance at 560 nm increased during the oxidation of AsA, suggested the formation of $O_2\bar{{\bullet}}$in methanol solution. Thus, the formation of $O_2\bar{{\bullet}}$ was confirmed during the autoxidation of AsA not only in aqueous solution but also in methanol solution in the presence heavy metal ions.

• Archives of Reconstructive Microsurgery
• /
• v.15 no.1
• /
• pp.1-9
• /
• 2006

The purpose of this study is to determine the effects of selective inducible nitric oxide synthase (iNOS) inhibitor N-[3-aminomethyl]benzyl]acetamidine (l400W) on the reperfused cremaster muscle. The extracellular superoxide dismutase knockout ($EC-SOD^{-/-}$) mice was used to make the experimental window for ischemia-reperfusion injury. The muscle was exposed to 4.5 h of ischemia followed by 90 min of reperfusion and the mice received either 3 mg/kg of 1400W or the same amount of phosphate buffered saline (PBS) subcutaneously at 10 min before the start of reperfusion. The results showed that 1400W treatment markedly improved the recovery of the vessel diameter and blood flow in the reperfused cremaster muscle compared to that of PBS group. Histological examination showed reduced edema in the interstitium and muscle fiber, and reduced nitrotyrosine formation (a marker of total peroxinitrite ($ONOO^-$) in 1400W-treated muscle compared to PBS. Our results suggest that iNOS and $ONOO^-$ products are involved in skeletal muscle I/R injury. Reduced I/R injury by using selective inhibition of iNOS is perhaps via limiting cytotoxic $ONOO^-$ generation, a reaction product of nitric oxide (NO) and superoxide anion ($O_2^-$). Thus, inhibition of iNOS appears to be a good treatment strategy in reducing clinical I/R injury.

• 대한생식의학회:학술대회논문집
• /
• 2000.06a
• /
• pp.13-28
• /
• 2000

Human spermatozoa exhibit a capacity to generate ROS and initiate peroxidation of the unsaturated fatty acids in the sperm plasma membrane, which plays a key role in the etiology of male infertility. The short half-life and limited diffusion of these molecules is consistent with their physiologic role in key biological events such as acrosome reaction and hyperactivation. The intrinsic reactivity of these metabolites in peroxidative damage induced by ROS, particularly $H_2O_2$ and the superoxide anion, has been proposed as a major cause of defective sperm function in cases of male infertility. The number of antioxidants known to attack different stages of peroxidative damage is growing, and it will be of interest to compare alpha-tocopherol and ascorbic acid with these for their therapeutic potential in vitro and in vivo. Both spermatozoa and leukocytes generate ROS, although leukocytes produce much higher levels. The clinical significance of leukocyte presence in semen is controversial. Seminal plasma confers some protection against ROS damage because it contains enzymes that scavenge ROS, such as catalase and superoxide dismutase. A variety of defense mechanisms comprising a number of antioxidants can be employed to reduce or overcome oxidative stress caused by excessive ROS. Determination of male infertility etiology is important, as it will help us develop effective therapies to overcome excessive ROS generation. ROS can have both beneficial and detrimental effects on the spermatozoa and the balancing between the amounts of ROS produced and the amounts scavenged at any moment will determine whether a given sperm function will be promoted or jeopardized. Accurate assessment of ROS levels and, subsequently, OS is Vital, as this will help clinicians both elucidate the fertility status and identify the subgroups of patients that respond or do not respond to these therapeutic strategies. The overt commercial claims of antioxidant benefits and supplements for fertility purposes must be cautiously looked into, until proper multicentered clinical trials are studied. From the current data it appears that no Single adjuvant will be able to enhance the fertilizing capacity of sperm in infertile men, and a combination of the possible strategies that are not toxic at the dosage used would be a feasible approach.

• Journal of Applied Biological Chemistry
• /
• v.42 no.1
• /
• pp.40-44
• /
• 1999

The in vitro antioxidative activities of the 33 plant-derived essential oils and 37 phytochemicals including 3 Mentha arvensis leaf-, 2 Thymus vulgaris leaf- and 2 Syzygium aromaticum flower-derived isolates were determined by the inhibition of linoleic acid autoxidation, the generation of superoxide anion and scavenging of DPPH radical. They were then compared to those of the widely used plant-derived antioxidants (pyrogallol and quercetin) and synthetic antioxidant BHT. At a concentration of 0.01%, potent antioxidative effect was observed in the essential oils from Cinnamomum cassia roots, Mentha arvensis leaves, Ginkgo biloba fruits, and Syzygium aromaticum flowers. Of the phytochemicals used, eugenol and isoeugenol at 0.01% showed potent antioxidative activity, and their activities were comparable to those of pyrogallol, quercetin, and BHT. The Cinnamomum root-, the Mentha leaf-, the Ginkgo fruit-, and the Syzygium flower-derived materials may be a good source for an alternative to the currently used antioxidants.

• The Journal of Internal Korean Medicine
• /
• v.28 no.1
• /
• pp.80-91
• /
• 2007

Objectives : Peroxynitrite (ONOO-), superoxide anion radical (?O2-) and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging process, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer and atherosclerosis. The aim of this study was to investigate Sabohwan's activity for scavenging ONOO- and its precursors. NO and ?02-. Methods : For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4.5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Results : Sabohwanblocked tert-butylhydroperoxide (t-BHP)-induced cell death in a dose-dependent fashion. It scavenged t-BHP-induced ONOO-, NO and ?O2- in YPEN cells. Sabohwan inhibited the generation of ONOO-, NO and ?O2- in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondria both in vitro and in vivo. The lipid peroxide level increased and glutathione level decreased in the LPS-treated mice, whereas the ones in the Sabohwanadministered group among the LPS-treated mice reversed toward their natural levels. Conclusions : These results suggest that Sabohwanis an effective ONOO-, ?O2- and NO scavenger, and thereby it might have a potential role as a therapy against the aging process and age-related diseases.

• Environmental Analysis Health and Toxicology
• /
• v.10 no.1_2
• /
• pp.47-54
• /
• 1995

To investigate and evaluated the scavenging and antioxidative effects of various flavonoids on paraquat induced toxicity, in vivo and vitro tests of eight flavonoids (catechin, epocatechin, flavone, chrysin, apigenin, quercetin, morin and biochanin A) were carried out. The generation of reactive oxygen substances(ROS) in PMS-NADH system $H_2O_2$ induced hemolysis and lipidperoxidation to blood, NADPH dependent lipidperoxidation to liver and lung microsome by paraquat were studied.The results are summerized as follows; 1) In the concentration ranges from 3.3 to 9.8$\mu$M of catechin,epicatechin, quercetin and biochanin A removed the 50% of DPPH radical scavenging effects. 2) In the concentration ranges from 0.60 to 1.86 mM of catechin, epicatechin, quercetin and biochanin A showed the inhibitory and antioxidative activity on superoxide anion which gernerated in PMA-NADH system. 3) In the concentration ranges from 0.12 to 0.49mM of catechin, epicatechin, quercetin and biochanin A showed the inhibitory and antioxidative activity on H202 which generated in PMA-NADH system. 4) In the concentration ranges from 0.6 x10$^{-5}$ to 6.3 x 10$^{-5}$mM of catechin, epicatechin, flavone, chrysin, quercetin and morin showed the inhibitory and antioxidative activity on $H_2O_2$ induced hemolysis to blood 5) All flavonoids tested exhibited inhibitory and antioxidative effects on paraquat induced liver and tung microsomal lipidperoxidation. Therefore, all flavonoids evaluated showed the useful compounds for scavenger and antioxidant on paraquat induced toxicity.