세균의 활성산소종과 활성질소종에 대한 내성에서 NADH dehydrogenase-2 결손의 효과

박희정(Hee Jeong Park),채권석(Kwon Seok Chae),방일수(Iel Soo Bang) 대한구강악안면병리학회 2010 대한구강악안면병리학회지 Vol.34 No.6

The electron transport chain (ETC) delivers electrons from many substrates to reduce molecular oxygen to water. ETC accomplishes the stepwise transfer of electrons through series of protein complexes conferring oxidation-reduction reactions with concomitant transport of proton across membrane, generating a proton gradient which leads ATP synthesis by F0F1ATPase. Bacterial ETC initiates with oxidation of NADH by NADH dehydrogenase complex (complex Ⅰ). Therefore, damage of complex Ⅰ leads to insufficient function of ETC and accumulation of NADH inside the cell. Contribution of ETC activity and its consequent changes of NADH levels to bacterial damage response against reactive oxygen and nitrogen species (ROS/RNS) has been poorly understood. In this study, by constructing ndh mutant Salmonella lacking complex Ⅰ NADH dehydrogenase 2, we evaluated the effect of ETC deficiency to bacterial resistance against ROS and RNS. The growth of ndh mutant Salmonella is impaired in the culture media containing hydrogen peroxide, but rather accelerates in the media containing nitric oxide donors. Data suggest that redox potential of NADH accumulated inside the cell by ETC blockage may affect inversely to bacterial resistance against reactive oxygen species and reactive nitrogen species.

Mechanisms of Noise-Induced Hearing Loss and Treatment

최철희 한국청각언어재활학회 2011 Audiology and Speech Research Vol.7 No.2

Noise-induced hearing loss (NIHL) means hearing loss or cochlear damage induced by either a short exposure to an intense impulse sounds from 100 to 150 dB SPL or continuous exposure to loud sounds at or above 85 dB SPL over relatively long period of time. Noise exposure results in oxidative stress destroying the antioxidant defense mechanism in the cochlea by over-production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and other free radicals. The purpose of this study is to explain the basic mechanisms of NIHL and to review a target and the site of action of treatment in terms of free radical formation. Oxidative stress begins immediately after noise exposure and continues up to 21 days after the exposure. Cell death process progresses after noise exposure. A primary cell death pathway following noise exposure is called apoptosis. Pharmacological approaches for prevention or treatment of NIHL have been developed with both oxygen-based antioxidant drugs inhibiting the generation of ROS and nitrogen-based antioxidant drugs inhibiting the production of RNS. There are synergistic effects of combined antioxidant drugs because each antioxidant drug may target different treatment mechanism. When one antioxidant drug was used in combination with other antioxidant drugs, the amount of reduction was analyzed and described. In addition, the optimal timing of therapeutic effects of antioxidant drugs depends on the time of initial treatment and the length of treatment before and after noise exposure. The maximal effect of treatment was observed in treatment for 9 days with injection starting at 24 h after noise exposure. The treatment of antioxidant drugs extending up to 10 days after noise exposure can reduce cumulative cochlear damage resulting from the delayed formation of free radicals. However, the relationship between free radical formation and the optimal timing of treatment is still unclear. Further studies on the relationship should be continually performed because of clinical usefulness and its importance.

Preliminary Study of the Therapeutic Effect of a Nitrone-Based Antioxidant Drug (HPN-07) on Acute Acoustic Trauma

최철희(Chul-Hee Choi) 한국언어청각임상학회 2011 Communication Sciences and Disorders Vol.16 No.2

배경 및 목적: 급성음향외상(Acute acoustic trauma)은 활성산소기(reactive oxygen species, ROS), 활성질소기(reactive nitrogen species, RNS), 그리고 다른 유리기(other free radicals) 의 초과 생산으로 내이의 와우의 항산화방어기제 능력을 초과하는 산화적 스트레스(oxidative stress)를 만든다. 최근 급성음향외상에 발생하는 와우손상을 예방하거나 치료하는 약리학적 접근이 발전되어오고 있다. 본 논문은 질소에 기초한 항산화제인 HPN-07 [4-hydroxy Phenyl-N-tert-butylnitrone (4-OHPBN)의 파생약품]의 급성음향외상 치료효과를 조사하는데 목적을 두고 있다. 방법: 각 집단에 여섯 마리의 친칠라를 통제군, HPN-07치료군, 그리고 HPN-07과 NAC (N-acetyl-L-cystein) 치료군으로 무작위로 할당하여 모든 집단의 동물들을 4 ㎑ 중심에 놓여진 옥타브당 -12 ㏈를 가진 옥타브밴드 소음을105 ㏈의 강도로 6시간 동안 노출 시켰다. 두 실험 집단의 동물들은 소음노출 후 4시간 경과 후 입으로 약물을 먹었고, 그 후 2일 동안 하루에 두 번 아침 저녁으로 계속 먹었다. 소음 노출 전과 후 21일에 측정된 청성뇌간 반응(auditory brainstem response, ABR)의 차이로 계산된 영구적인 청력역치가 얻어졌고 그것이 통계학적으로 분석되었다. 결과: 고주파수(2-8 ㎑)의 평균으로 계산된 영구적인 청력역치변화(permanent hearing threshold shifts)는 HPN-07 치료집단과 HPN-07과 NAC 치료 집단은 소음에만 노출된 통제집단보다 유의미하게 차이가 있었고 두 치료집단 사이에도 유의미한 차이가 나타났다 (p < 0.05). 통제집단의 영구적인 청력역치변화는 36 ㏈인데 반해 HPN-07치료집단은 26 ㏈로 줄어들었고 HPN-07과 NAC 치료를 모두 받은 집단은 약 11 ㏈로 감소하였다. 게다가 HPN-07과 NAC 치료집단의 영구적인 청력역치변화는 4-OHPBN과 NAC 치료그룹과의 거의 비슷하였다. 논의 및 결론: HPN-07은 영구적인 청력역치변화를 떨어뜨렸고 HPN-07과 NAC 치료집단이 가장 높은 치료효과를 보여 주었다 (p < 0.05). 이것은 HPN-07과 NAC와의 결합은 급성음향외상을 치료하는데 효과적이며 다른 항산화제와의 결합은 그 큰 치료효과를 가져올 수 있음을 증명한다. 비록 본 연구가 정확한 활동기저를 보여주지는 않았지만 HPN-07은 유리기의 활동을 제거하는 약물로 효과적으로 사용될 수 있음을 보여주었다. Background & Objectives: Acute acoustic trauma (AAT) results in oxidative stress exceeding the capacity of the antioxidant defense mechanisms in cochlea by excessive production of reactive oxygen species, reactive nitrogen species, and other free radicals. Pharmacological approaches have been developed to prevent or treat cochlear injury induced by AAT. The present study aims to investigate if another nitrogen-based antioxidant drug, HPN-07 [a derivative of 4-hydroxy phenyl-N-tert-butyl Nitrone (4-OHPBN)] can be used to treat the permanent hearing loss induced by AAT. Method: Eighteen female chinchillas (six for each group) were exposed to a 105 ㏈ octave-band noise centered at 4 ㎑ for 6 h. HPN-07 and HPN-07 plus N-acetyl-L-cystein (NAC) were orally administered to two experimental groups giving a first injection 4 h after noise exposure and continually injecting twice daily for the next two days. Auditory brainstem responses (ABR) before noise exposure and 21 days after noise exposure were obtained and analyzed for permanent hearing threshold shifts. Results: Results showed that the mean permanent hearing threshold shifts averaged at higher frequencies (2-8 ㎑) for HPN-07 treated group (26 ㏈) and HPN-07 plus NAC treated groups (11 ㏈) were significantly decreased compared to the noise exposure group (control group, 36 ㏈). In addition, significant differences between HPN-07 treated group and HPN-07 plus NAC treated groups were also found. Discussion & Conclusion: HPN-07 reduced permanent hearing threshold shifts and HPN-07 plus NAC showed greater effects. These results demonstrate that HPN-07 and the combination of HPN-07 with NAC can treat acute acoustic trauma and the drug combination increase the therapeutic effect. The therapeutic effect of HPN-07 may result from its role as a free radical scavenger.

병원성 살모넬라의 활성산소종과 활성질소종에 대한 내성에서 글루타치온 합성효소의 역할

방일수 대한구강악안면병리학회 2008 대한구강악안면병리학회지 Vol.32 No.1

Intracellular pathogens must maintain redox homeostasis against the antimicrobial actions of reactive oxygen and nitrogen species produced by host cells. This study proves that glutathione is required to promote survival of an enteric pathogen Salmonella under the conditions producing reactive oxygen or nitrogen species. Glutathione is the non-protein thiol compound distributed in a variety of organisms and possesses strong electron-donating capability to reduce intracellular redox environment. To examine the role of glutathione on Salmonella redox homeostasis under oxidative and nitrosative stress conditions, gshB gene encoding glutathione synthetase was mutated by the one-step PCR inactivation method. The growth of gshB mutant Salmonella producing virtually no glutathione was greatly impaired in the culture media containing either hydrogen peroxide or nitric oxide donors. The results suggest that physiological levels of glutathione can provide a fundamental capability to maintain redox homeostasis for Salmonella in surviving oxidizing conditions of host cells.

Review of the Current State of Medical Plasma Technology and its Potential Applications

문익준,Chong Hyun Won 대한의학레이저학회 2018 MEDICAL LASERS Vol.7 No.1

Plasma technology is entering a new chapter through medical use. Medical devices based on plasma technology have recently been tested for the biochemical effects of plasma on cells and tissues. The implementation of plasma technology in medicine was made possible by the introduction of non-thermal, cold plasma emitted at atmospheric pressure. To date, the putative biological effects of plasma include decontamination, disinfection, tooth bleaching and accelerated wound healing. In addition, cold plasma treatment has some potential as a novel cancer therapeutic. Plasma is currently believed to exert its diverse effects mainly by regulating both intra-and extracellular oxidationreduction reactions as a result of the generation of reactive oxygen and nitrogen species. Interestingly, the biological effects of plasma exhibited hormesis, which is a biphasic response depending on the degree or amount of exposure. Ongoing investigations focus largely on elucidating how the modulation of oxidation-reduction by plasma affects the behavior of cells and helps determine the optimal treatment parameters maximizing the favorable effects of cold plasma. Although accumulating evidence indicates the role of cold plasma as the next-generation therapeutic in various medical fields, more detailed characterization of the biomolecular effects of plasma appears to be the next critical step, along with clinical studies designed to validate its clinical efficacy and safety.

The known and unknown sources of reactive oxygen and nitrogen species in haemocytes of marine bivalve molluscs

Donaghy, L.,Hong, H.K.,Jauzein, C.,Choi, K.S. Academic Press 2015 FISH AND SHELLFISH IMMUNOLOGY Vol.42 No.1

Reactive oxygen and nitrogen species (ROS and RNS) are naturally produced in all cells and organisms. Modifications of standard conditions alter reactive species generation and may result in oxidative stress. Because of the degradation of marine ecosystems, massive aquaculture productions, global change and pathogenic infections, oxidative stress is highly prevalent in marine bivalve molluscs. Haemocytes of bivalve molluscs produce ROS and RNS as part of their basal metabolism as well as in response to endogenous and exogenous stimuli. However, sources and pathways of reactive species production are currently poorly deciphered in marine bivalves, potentially leading to misinterpretations. Although sources and pathways of ROS and RNS productions are highly conserved between vertebrates and invertebrates, some uncommon pathways seem to only exist in marine bivalves. To understand the biology and pathobiology of ROS and RNS in haemocytes of marine bivalves, it is necessary to characterise their sources and pathways of production. The aims of the present review are to discuss the currently known and unknown intracellular sources of reactive oxygen and nitrogen species in marine bivalve molluscs, in light of terrestrial vertebrates, and to expose principal pitfalls usually encountered.

Reactive Oxygen and Nitrogen Species in Pathogenesis of Vascular Complications of Diabetes

손석만 대한당뇨병학회 2012 Diabetes and Metabolism Journal Vol.36 No.3

Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in subjects with diabetes. Disorders of the physiological signaling functions of reactive oxygen species (superoxide and hydrogen peroxide) and reactive nitrogen species (nitric oxide and peroxynitrite) are important features of diabetes. In the absence of an appropriate compensation by the endogenous antioxidant defense network, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause cellular damage and contribute to the vascular complications of diabetes. It has recently been suggested that diabetic subjects with vascular complications may have a defective cellular antioxidant response against the oxidative stress generated by hyperglycemia. This raises the concept that antioxidant therapy may be of great benefit to these subjects. Although our understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. Thus, further investigation of therapeutic interventions to prevent or delay the progression of diabetic vascular complications is needed.

Glutathione Dimerization-Based Plasmonic Nanoswitch for Biodetection of Reactive Oxygen and Nitrogen Species

Kumar, Sumit,Rhim, Won-Kyu,Lim, Dong-Kwon,Nam, Jwa-Min American Chemical Society 2013 ACS NANO Vol.7 No.3

<P>Reactive oxygen and nitrogen species (ROS and RNS) are continuously produced in the cellular systems and are controlled by several antioxidant mechanisms. Here, we developed a straightforward, sensitive, and quantitative assay for the colorimetric and spectroscopic detection of various ROS and RNS such as H<SUB>2</SUB>O<SUB>2</SUB>, ·OH, <SUP>–</SUP>OCl, NO<B>·</B>, and O<SUB>2</SUB><SUP>–</SUP> using glutathione-modified gold nanoparticles (GSH-AuNPs). A basic principle here is that the GSHs on the AuNP surface can be readily detached <I>via</I> the formation of glutathione disulfides upon the addition of ROS and RNS, and destabilized particles can aggregate to generate the plasmonic couplings between plasmonic AuNPs that trigger the red shift in UV–vis spectrum and solution color change. For nonradical species such as H<SUB>2</SUB>O<SUB>2</SUB>, this process can be more efficiently achieved by converting them into radical species <I>via</I> the Fenton reaction. Using this strategy, we were able to rapidly and quantitatively distinguish among cancerous and normal cells based on ROS and RNS production.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2013/ancac3.2013.7.issue-3/nn305250p/production/images/medium/nn-2012-05250p_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn305250p'>ACS Electronic Supporting Info</A></P>

NecroX as a Novel Class of Mitochondrial Reactive Oxygen Species and ONOO− Scavenger

Hyoung Jin Kim,Sun Young Koo,Bong-Hyun Ahn,Oeuk Park,Doo Hoe Park,Dong Ook Seo,Jong Heon Won,Hyeon Joo Yim,Hyo-Shin Kwak,Heui Sul Park,정철웅,Young Leem Oh,Soon Ha Kim 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.11

Mitochondrial reactive oxygen species and reactive nitrogen species are proven to be major sources of oxidative stress in the cell; they play a prominent role in a wide range of human disorders resulting from nonapoptotic cell death. The aim of this study is to examine the cytoprotective effect of the NecroX series against harmful stresses, including pro-oxidant (tertiarybutylhydroperoxide), doxorubicin, CCl4, and hypoxic injury. In this study, these novel chemical molecules inhibited caspase-independent cell death with necrotic morphology, which is distinctly different from apoptosis, autophagy, and necroptosis. In addition, they displayed strong mitochondrial reactive oxygen species and ONOO− scavenging activity. Further, oral administration of these molecules in C57BL/6 mice attenuated streptozotocin-induced pancreatic islet β-cell destruction as well as CCl4-induced hepatotoxicity in vivo. Taken together, these results demonstrate that the NecroX series are involved in the blockade of nonapoptotic cell death against mitochondrial oxidative stresses. Thus, these chemical molecules are potential therapeutic agents in mitochondria-related human diseases involving necrotic tissue injury.

Scavenging activity of Curcuma caesia rhizome against reactive oxygen and nitrogen species

Indrajit Karmakar,Narayan Dolai,Pathik Saha,Nilanjan Sarkar,Asis Bala,Pallab Kanti Haldar 경희대학교 융합한의과학연구소 2011 Oriental Pharmacy and Experimental Medicine Vol.11 No.4

Curcuma caesia Roxb. (Zingiberaceae), known as black turmeric in English, is a perennial herb found throughout the Himalayan region, North-East and Central India. The plant has been traditionally used in India for several medicinal purposes. Present study was carried out to evaluate the methanol extract of C. caesia (MECC) rhizome for some in vitro antioxidant studies as because we know that many diseases are associated with reactive oxygen species (ROS) and reactive nitrogen species (RNS). Effect of MECC on ROS and RNS were evaluated in different in vitro methods like 1, 1-diphenyl-2-picrylhydrazil radical, hydroxyl radicals, superoxide anions, nitric oxide, hydrogen peroxide,peroxynitrite and hypochlorous acid. Lipid peroxidation,total phenolic content was also measured by standard assay method. The extract showed significant antioxidant activities in a dose dependent manner. The IC_(50) values for scavenging of free radicals were 94.03±0.67 μg/ml, 155.59±3.03 μg/ml,68.10±1.24 μg/ml, 21.07±1.78 μg/ml, 260.56±12.65 μg/ml and 33.33±0.52 μg/ml for DPPH, nitric oxide, superoxide,hydroxyl, peroxynitrite and hypochlorous acid respectively. Reductive ability of the extract was also tested where dose dependent reducing capability was observed. The rhizome extract contains 677.7 μg of phenolic compound in 10 mg of the extract which is accounted for its free radical as well as antioxidant activity. From the above study it is concluded that the methanol extract of C. caesia rhizome is a potential source of natural antioxidant.