Effect of Lipid Peroxidation on the Fluidity of Erythrocyte Ghost and Phospholipid Liposomal Membranes

Han, Suk-Kyu,Kim, Min,Park, Yeong-Hun,Park, Eun-Ju,Lee, Jeong-Hee The Pharmaceutical Society of Korea 1992 Archives of Pharmacal Research Vol.15 No.4

The effects of lipid peroxidation on the fluidity of the lipid bilayers of the human erythrocyte ghosts and egg-lecithin phospholipid liposomes have been studied. For the measurements of the peroxidation extent and the fluidity of the membranes, the thiobarbituric acid-reactive substances and the fluorescence depolarization of 1, 6-diphynyl-1, 3, 5-hexatriene labelled into the membrane were employed, respectively. The lipid peroxidation was performed in hypoxanthine/xanthine oxidase/ferrous ion, and hydrogen peroxide/ferrous ion systems. The results of these experiments show that both of the xanthine oxidase and hydrogen peroxide systems effectively. The lipid peroxidation decreased the fluidity of the membranes, especially at the very early stage of the peroxidation reaction. The decrease in the fluidity of membrane by the lipid peroxidation has been ascribed to the alteration of the polyunsaturated acyl chains of lipids and cross linkages among the membrane components. However, under drastic condition of lipid peroxidation, tdhe fluidity of the membrane rather increased possibly due to the deterioration of the membrane integrity by the peroxidation. Morphological change of the erythrocyte on peroxidation has also been observed.

Reaction of ferritin with hydrogen peroxide induces lipid peroxidation

Yoon, Hung-Hwan,Lee, Myeong-Seon,Kang, Jung-Hoon Korean Society for Biochemistry and Molecular Biol 2010 BMB Reports Vol.43 No.3

Lipid peroxidation is known to be an important factor in the pathologies of many diseases associated with oxidative stress. We assessed the lipid peroxidation induced by the reaction of ferritin with $H_2O_2$. When linoleic acid micelles or phosphatidyl choline liposomes were incubated with ferritin and $H_2O_2$, lipid peroxidation increased in the presence of ferritin and $H_2O_2$ in a concentration-dependent manner. The hydroxyl radical scavengers, azide and thiourea, prevented lipid peroxidation induced by the ferritin/$H_2O_2$ system. The iron specific chelator desferoxamine also prevented ferritin/$H_2O_2$ systemmediated lipid peroxidation. These results demonstrate the possible role of iron in ferritin/$H_2O_2$ system-mediated lipid peroxidation. Carnosine is involved in many cellular defense processes, including free radical detoxification. In this study, carnosine, homocarnosine, and anserine were shown to significantly prevent ferritin/$H_2O_2$ system-mediated lipid peroxidation and also inhibited the free radical-generation activity of ferritin. These results indicated that carnosine and related compounds may prevent ferritin/$H_2O_2$ system-mediated lipid peroxidation via free radical scavenging.

피지내 과산화지질이 기미와 여드름의 치료에 미치는 영향

오지원,함정희 梨花女子大學校 醫科大學 醫科學硏究所 1991 EMJ (Ewha medical journal) Vol.14 No.3

To evaluate correlation between the amounts of lipid peroxide in skin surface lipid and clinical aspect of lipid-relating cutaneous disorders, such as melasma and acne, skin surface lipid samples were collected by using cup method from the faces of 20 acne women and 20 melasma women, before and 3 months after topical treatment with 2% hydroquinone and 2.5% benzoyl peroxide, respectively. The amounts of total lipids and lipid peroxide in skin surface lipid were measured by spectrophotometer and statistically analyzed by student's t-test. The results were as follows; 1) Before treatmentin comparison with control group, melasma group showed increase of the amounts of lipid peroxide and the ratio of lipid peroxide to total lipids. But acne group showed significant increase of the ratio of lipid peroxide to total lipids as well as the amounts of total lipids and lipid peroxide. 2) After treatment, in comparison with pretreatment, melasma group showed significant decrease of the amounts of lipid peroxide and the ratio of lipid peroxide to total lipids. And in acne group, the amounts of total lipids and lipid peroxide were also decreased significantly. The amounts of lipid peroxide in skin surface lipid decreased at the time of improvements of clinical aspects in melasma and acne. This data suggest that clinical aspect of melasma and acne is related to the amounts of lipid peroxide in skin surface lipid.

Lipid Peroxidation Induced by the Reaction of Cytochrome c with Hydrogen Peroxide

Kang, Jung-Hoon Korean Chemical Society 2006 Bulletin of the Korean Chemical Society Vol.27 No.6

Lipid peroxidation induced by the reaction of cytochrome c with $H_2O_2$ was investigated. When linoleic acid micelles or phosphatidyl choline liposomes were incubated with cytochrome c and $H_2O_2$, lipid peroxidation was increased in cytochrome c and $H_2O_2$ concentrations-dependent manner. Radical scavengers, azide, formate and ethanol prevented lipid peroxidation induced by the cytochrome c/$H_2O_2$ system. Iron specific chelator, desferoxamine also prevented the cytochrome c/$H_2O_2$ system-mediated lipid peroxidation. These results suggest that lipid peroxidation may be induced by the cytochrome c/$H_2O_2$ system via the generation of free radicals. Carnosine, homocarnosine and anserine are present in the muscle and brain of many animals and human. Previous studies show that these compounds have an antioxidant function. In the present study, carnosine, homocarnosine and anserine significantly prevented the cytochrome c/$H_2O_2$ system-mediated lipid peroxidation. Carnosine and related compounds also inhibited the free radical-generating activity of cytochrome c. The results suggest that carnosine, homocarnosine and anserine may prevent lipid peroxidation induced by the cytochrome c/$H_2O_2$ system through a free radical scavenging.

뇌경색후 Lipid Peroxidation에 미치는 Allopurinol 및 Deferoxamine의 효과에 대한 실험적 연구

권택현,박윤관,정용구,정흥섭,서중근,이훈갑,주정화,이기찬 대한신경외과학회 1992 Journal of Korean neurosurgical society Vol.21 No.1

It has been hypothesized that ischemia, followed by reperfusion, facilitates peroxidative free radical chain process in brain. This study was undertaken to investigate the effect of allopurinol and deferoxamine on cerebral lipid peroxidation, estimated by a thiobarbituric acid test, following transient bilateral forebrain ischemia in the rat model of four vessel occlusion. Sprague-Dawley rats fed ad libitum were subjected to transient but severe forebrain ischemia by permanently occluding the vertebral arteries and 48 hours later temporarily occluding the common carotid arteries for 20minutes. Carotid artery blood flow was restored and rats were decapitated after 48 hours. We assessed the lipid peroxidation capacity of cerebral homogenates obtained from hippocampus, basal ganglia, cortex and thalamus. The homogenates were subjected to 30 minutes of aerobic incubation. The production of lipid peroxides were decreased in all sampled area in the treated groups compared with the control group. Allopurinol and deferoxamine-treated groups showed decreased lipid peroxide levels in all the sampled area, but especially more in the hippocampus, (p=0.02), (p<0.01) repecxtively. Combined group (allopurinol and deferoxamine) showed decreased lipid peroxide levels in all the sampled area, but was not statistcally significant(p>0.05). The results suggest that allopurinol and deferoxamine play a role in protecting ischemic cellular damages by scavenging free radicals and subsequently lipid peroxides formed by oxygen supply through blood reperfusion.

Effects of Nitrofurantoin on Lipid Peroxidation and Reactive Oxygen Radical Generation in Porcine Lung Microsome

백재승,김시황,김혜원,정명희,김명석,Paick, Jae-Seung,Kim, Si-Whang,Kim, Hae-Won,Chung, Myung-Hee,Kim, Myung-Suk The Korean Society of Pharmacology 1985 대한약리학잡지 Vol.21 No.1

항균제 nitrofurantion에 의한 폐독작용의 생화학적 기전을 규명하기 위한 연구 일환으로 in vitro에서 폐장 microsome 지질의 과산화 및 반응성 산소 radical $(O^{-}_{2}{\cdot},\;H_2O_2,\;OH{\cdot},\;^1O_2)$의 생성에 대한 nitrofurantion의 영향과 양자 간의 상호 관련성을 검토하였다. Nitrofurantion은 호기성 반응 조건에서 돼지 폐장 microsome의 NADPH 의존성 지질 과산화를 용량 의존적으로 증가시킬 뿐 아니라 $O^{-}_{2}{\cdot},\;H_2O_2$ 및 두 radical의 상호 작용으로 2차적으로 형성되는 $OH{\cdot}$의 생성 또한 촉진하였으며 $^1O_2$생성은 관찰되지 않았다. 이와 같은 폐장 microsome지질 과산화 증가는 SOD 및 catalase에 의하여 억제될 뿐만 아니라 $OH{\cdot}$ 제거 물질인 mannitol, thiourea에 의하여도 현저히 억제되었으며, $^1O_2$ 제거 물질에 의하여는 영향을 받지 않았던 한편 염기성 반응 조건에서는 nitrofurantoin에 의한 지질 과산화가 관찰되지 않았다. 이상의 결과로 미루어 보아 nitrofurantoin은 폐장 microsome의 NADPH 의존적이 반응성산소 radical $(O^{-}_{2}{\cdot},\;H_2O_2$ 및 $OH{\cdot})$의 생성을 증가시키며 이들 중 특히 $OH{\cdot}$ 에 의한 microsome막 지질 과산화를 촉진하는 것으로 결론지었고, 이와 같은 in vivo 현상은 nitrofurantion의 in vitro 폐독작용의 기전을 설명하는 일부가 될 것으로 사료하였다. In vitro effects of nitrofurantoin, an antimicrobial agent for acute and chronic urinary tract infection, on the lung microsomal lipid peroxidation and the generation of reactive oxygen radicals were investigated to elucidate the biochemical mechanisms of its in vivopulmonary toxicity. The interaction of nitrofurantoin with porcine lung microsome resulted in significant lipid peroxidation. In addition, nitrofurantoin stimulated the generation of reactive oxygen radicals, $O^{-}_{2}{\cdot},\;H_2O_2$ as well as a highly reactive secondary oxygen species, $OH{\cdot}$. The stimulation of lipid peroxidation was inhibited not only by superoxide dismutase and catalase, but also by hydroxyl radical scavengers, mannitol and thiourea. Neither singlet oxygen $({^1}O_{2})$ was detected during the incubation of microsome with nitrofurantoin, nor lipid peroxidation was inhibited by singlet oxygen scavengers. When incubated anaerobically under the nitrogen atmosphere, the ability of nitrofurantoin to stimulatle lipid peroxidation was abolished. It appears that NADPH-dependent metaboliam of nitrofurantoin in pulmonary microsome under aerobic condition is accompanied by the stimulation of lipid peroxidation through the mediation of reactive oxygen radicals, particularly hydroxyl radical. It is strongly suggested from these results that the stimulation of pulmonary microsomal lipid peroxidation by the reactive oxygen radical may be a in vivo mechanism of pulmonary toxicity caused by nitrofurantoin.

OxyR Regulon Controls Lipid Peroxidation-mediated Oxidative Stress in Escherichia coli

Yoon, Seon-Joo,Park, Ji-Eun,Yang, Joon-Hyuck,Park, Jeen-Woo 생화학분자생물학회 2002 Journal of biochemistry and molecular biology Vol.35 No.3

Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. The oxyR gene product regulates the expression of enzymes and proteins that are needed for cellular protection against oxidative stress. Upon exposure to tert-butylhydroperoxide (t-BOOH) and 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH), which induce lipid peroxidation in membranes, the Escherichia coli oxyR overexpression mutant was much more resistant to lipid peroxidation-mediated cellular damage, when compared to the oxyR deletion mutant in regard to growth kinetics, viability, and DNA damage. The deletion of the oxyR gene in E. coli also resulted in increased susceptibility of superoxide dismutase to lipid peroxidation-mediated inactivation. The results indicate that the peroxidation of lipid is probably one of the important intermediary events in free radical-induced cellular damage. Also, the oxyR regulon plays an important protective role in lipid peroxidation-mediated cellular damage.

Nitrofurantion이 폐장 미크로솜 지질과산화와 반응성 산소 라디칼 생성에 미치는 영향

백재승(Jae-Seung Paick),김시황(Si-Whang Kim),김혜원(Hae-Won Kim),정명희(Myung-Hee Chung),김명석(Myung-Suk Kim) 대한약리학회 1985 대한약리학잡지 Vol.21 No.1

항균제 nitrofurantion에 의한 폐독작용의 생화학적 기전을 규명하기 위한 연구 일환으로 in vitro에서 폐장 microsome 지질의 과산화 및 반응성 산소 radical (O₂^-⋅, H₂O₂, OH⋅, ¹O₂)의 생성에 대한 nitrofurantion의 영향과 양자 간의 상호 관련성을 검토하였다. Nitrofurantion은 호기성 반응 조건에서 돼지 폐장 microsome의 NADPH 의존성 지질 과산화를 용량 의존적으로 증가시킬 뿐 아니라 O₂^-⋅, H₂O₂ 및 두 radical의 상호 작용으로 2차적으로 형성되는 OH⋅의 생성 또한 촉진하였으며 ¹O₂생성은 관찰되지 않았다. 이와 같은 폐장 microsome지질 과산화 증가는 SOD 및 catalase에 의하여 억제될 뿐만 아니라 OH⋅ 제거 물질인 mannitol, thiourea에 의하여도 현저히 억제되었으며, ¹O₂ 제거 물질에 의하여는 영향을 받지 않았던 한편 염기성 반응 조건에서는 nitrofurantoin에 의한 지질 과산화가 관찰되지 않았다. 이상의 결과로 미루어 보아 nitrofurantoin은 폐장 microsome의 NADPH 의존적이 반응성산소 radical (O₂^-⋅, H₂O₂ 및 OH⋅)의 생성을 증가시키며 이들 중 특히 OH⋅ 에 의한 microsome막 지질 과산화를 촉진하는 것으로 결론지었고, 이와 같은 in vivo 현상은 nitrofurantion의 in vitro 폐독작용의 기전을 설명하는 일부가 될 것으로 사료하였다. In vitro effects of nitrofurantoin, an antimicrobial agent for acute and chronic urinary tract infection, on the lung microsomal lipid peroxidation and the generation of reactive oxygen radicals were investigated to elucidate the biochemical mechanisms of its in vivopulmonary toxicity. The interaction of nitrofurantoin with porcine lung microsome resulted in significant lipid peroxidation. In addition, nitrofurantoin stimulated the generation of reactive oxygen radicals, O₂^-⋅, H₂O₂ as well as a highly reactive secondary oxygen species, OH⋅. The stimulation of lipid peroxidation was inhibited not only by superoxide dismutase and catalase, but also by hydroxyl radical scavengers, mannitol and thiourea. Neither singlet oxygen (¹O₂) was detected during the incubation of microsome with nitrofurantoin, nor lipid peroxidation was inhibited by singlet oxygen scavengers. When incubated anaerobically under the nitrogen atmosphere, the ability of nitrofurantoin to stimulatle lipid peroxidation was abolished. It appears that NADPH-dependent metaboliam of nitrofurantoin in pulmonary microsome under aerobic condition is accompanied by the stimulation of lipid peroxidation through the mediation of reactive oxygen radicals, particularly hydroxyl radical. It is strongly suggested from these results that the stimulation of pulmonary microsomal lipid peroxidation by the reactive oxygen radical may be a in vivo mechanism of pulmonary toxicity caused by nitrofurantoin.

Paraquat에 의한 산소 Radical 생성 및 지질과산화 작용의 Mouse 간 Submitochondria Particle과 Microsome에서의 비교

최중환(Jung-Hwan Choi),김용식(Yong-Sik Kim),박종완(Jong-Hwan Park),정명희(Myung-Hee Chung),윤종구(Chong-Ku Yunn) 대한약리학회 1991 대한약리학잡지 Vol.27 No.2

Paraquat 독성작용에 있어서 mitochondria의 잠재적인 역할을 평가하기 위하여, 이 약물의 산소 radical 생성과 지질과산화 반응에 미치는 영향을 mouse간의 submitochondrial particle 과 microsome에서 비교하여 보았다. Submitochondrial particle 사용시 NADH를, microsome 사용시 NADPH를 전자공여체로 이용한 경우 paraquat는 두 분획에서 superoxide anion과 hydrogen peroxide의 생성을 증가시켰다. 동일한 조건하에서 paraquat는 hydroxyl radical의 생성을 시사하는 methional로 부터 ethylene의 생성을 증가시켰다. 그러나, paraquat에 의한 이들 각각의 효과는 microsome에서 보다 submitochondrial particle에서 약간 낮았다. 한편, 두 분획 모두에서 paraquat는 지질과산화 반응을 촉진시켰다. Submitochondrial particle과 microsome에서의 Paraquat에 의한 지질과산화반응은 i) 두 분회에서 지질과산화는 SOD에 의해서 부분적으로 억제됨을 보였고, DETAPAC(iron chelator)에 의해서는 완전히 억제되었고, catalase와 hydroxyl radical scavenger에 의해서는 억제되지 아니하였으며, ii) 반응내ADP-Fe³⁺ 첨가로 paraquat에 의한 지질과산화는 더욱 증가되었지만 methional로 부터 ethylene 생성은 감소하여 hydroxyl radical 생성과 지질과산화 사이에는 상관성이 없음으로 보아 같은 기전을 통해 촉진됨을 알 수 있었고 이러한 촉진작용은 perferryl ion을 통하여 일어나리라 추측되었다. Submitochondrial particle에서 paraquat에 의해 촉진된 산소라디칼 생성과 지질과산화 반응은 p-hydroxymercuribenzoate(NADH dehydrogenase 억제제)에 의하여 억제되었으나 다른 respiratory chain 차단제들에 의해서는 거의 영향을 받지 않음으로 보아 mitochondria에서의 paraquat의 redox-cycling은 CoQ 보다는 NADH dehyrogenase와 관련이 있음을 시사하였다. 이상의 결과로 보아 산소 radical의 생성과 지질과산화를 유도하는 paraquat의 redox-cycling은 microsome에서와 마찬가지로 mitochondria에서도 일어나며, 이결과 생체내에서의 paraquat의 독작용에 관여함을 짐작할 수 있다. In order to evaluate a potential role of mitochondria in the mediation of toxicity of paraquat (PQ), submitochondrial particle and microsome of mouse liver were compared by oxygen radical generation and lipid peroxidation. With NADH in submitochondrial particle and NADPH in microsome as electron donors, PQ stimulated production of superoxide anion and H₂O₂ in both fractions. Under the same conditions, PQ enhanced the generation of ethylene from methional suggestiong stimulation of OH production by PQ. But these effects by PQ were somewhat lower in submitochondrial particle than in microsome. In addition, lipid peroxidation(measured as MDA production) was stimulated by PQ in both fractions. The stimulation of lipid peroxidation in both fractions seemed to occur by the same mechanism probably through perferryl ion. This was supported by the following findings: i) The lipid peroxidation in both fractions was partially inhibited by SOD and completely inhibited by DETAPAC(an iron chelator) but not by catalase or OH scavenger. ii) Addition of ADP-Fe³⁺ further increased PQ-induced lipid peroxidation but decreased ethylene production from methional suggesting no correlation between OH production and lipid peroxidation. The redox-cycling of PQ in mitochondria appeared to be linked to NADH dehydrogenase, not to CoQ since all of the observed stimulations by PQ in submitochondrial particle were inhibited by p-hydroxymercuribenzoate(a NADH dehydrogenase inhibitor) but not affected by other respiratory chain blockers. The above results demonstrate that redox-cycling properties of PQ leading to oxygen radical generation and lipid peroxidation can also occur in mitochondria in the same manner as in microsome. Therefore, the observed actions of PQ in mitochondria suggest that mitochondria may also contribute to toxicity of this drug in vivo.

Comparison of Paraquat Actions on Oxygen Radical Generation and Lipid Peroxidation between Submitochondrial Particle and Microsome of Mouse Liver

최중환,김용식,박종완,정명희,윤종구,Choi, Jung-Hwan,Kim, Yong-Sik,Park, Jong-Hwan,Chung, Myung-Hee,Yunn, Chong-Ku The Korean Society of Pharmacology 1991 대한약리학잡지 Vol.27 No.2

Paraquat 독성작용에 있어서 mitochondria의 잠재적인 역할을 평가하기 위하여, 이 약물의 산소 radical 생성과 지질과산화 반응에 미치는 영향을 mouse간의 submitochondrial particle 과 microsome에서 비교하여 보았다. Submitochondrial particle 사용시 NADH를, microsome 사용시 NADPH를 전자공여체로 이용한 경우 paraquat는 두 분획에서 superoxide anion과 hydrogen peroxide의 생성을 증가시켰다. 동일한 조건하에서 paraquat는 hydroxyl radical의 생성을 시사하는 methional로 부터 ethylene의 생성을 증가시켰다. 그러나, paraquat에 의한 이들 각각의 효과는 microsome에서 보다 submitochondrial particle에서 약간 낮았다. 한편, 두 분획 모두에서 paraquat는 지질과산화 반응을 촉진시켰다. Submitochondrial particle과 microsome에서의 Paraquat에 의한 지질과산화반응은 i) 두 분회에서 지질과산화는 SOD에 의해서 부분적으로 억제됨을 보였고, DETAPAC(iron chelator)에 의해서는 완전히 억제되었고, catalase와 hydroxyl radical scavenger에 의해서는 억제되지 아니하였으며, ii) 반응내 $ADP-Fe^{3+}$ 첨가로 paraquat에 의한 지질과산화는 더욱 증가되었지만 methional로 부터 ethylene 생성은 감소하여 hydroxyl radical 생성과 지질과산화 사이에는 상관성이 없음으로 보아 같은 기전을 통해 촉진됨을 알 수 있었고 이러한 촉진작용은 perferryl ion을 통하여 일어나리라 추측되었다. Submitochondrial particle에서 paraquat에 의해 촉진된 산소라디칼 생성과 지질과산화 반응은 p-hydroxymercuribenzoate(NADH dehydrogenase 억제제)에 의하여 억제되었으나 다른 respiratory chain 차단제들에 의해서는 거의 영향을 받지 않음으로 보아 mitochondria에서의 paraquat의 redox-cycling은 CoQ 보다는 NADH dehyrogenase와 관련이 있음을 시사하였다. 이상의 결과로 보아 산소 radical의 생성과 지질과산화를 유도하는 paraquat의 redox-cycling은 microsome에서와 마찬가지로 mitochondria에서도 일어나며, 이결과 생체내에서의 paraquat의 독작용에 관여함을 짐작할 수 있다. In order to evaluate a potential role of mitochondria in the mediation of toxicity of paraquat (PQ), submitochondrial particle and microsome of mouse liver were compared by oxygen radical generation and lipid peroxidation. With NADH in submitochondrial particle and NADPH in microsome as electron donors, PQ stimulated production of superoxide anion and $H_2O_2$ in both fractions. Under the same conditions, PQ enhanced the generation of ethylene from methional suggestiong stimulation of OH production by PQ. But these effects by PQ were somewhat lower in submitochondrial particle than in microsome. In addition, lipid peroxidation(measured as MDA production) was stimulated by PQ in both fractions. The stimulation of lipid peroxidation in both fractions seemed to occur by the same mechanism probably through perferryl ion. This was supported by the following findings: i) The lipid peroxidation in both fractions was partially inhibited by SOD and completely inhibited by DETAPAC(an iron chelator) but not by catalase or OH scavenger. ii) Addition of $ADP-Fe^{3+}$ further increased PQ-induced lipid peroxidation but decreased ethylene production from methional suggesting no correlation between OH production and lipid peroxidation. The redox-cycling of PQ in mitochondria appeared to be linked to NADH dehydrogenase, not to CoQ since all of the observed stimulations by PQ in submitochondrial particle were inhibited by p-hydroxymercuribenzoate(a NADH dehydrogenase inhibitor) but not affected by other respiratory chain blockers. The above results demonstrate that redox-cycling properties of PQ leading to oxygen radical generation and lipid peroxidation can also occur in mitochondria in the same manner as in microsome. Therefore, the observed actions of PQ in mitochondria suggest that mitochondria may also contribute to toxicity of this drug in vivo.