• Title/Summary/Keyword: Free radical mechanism

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Effect of Biphenyl Dimethyl Dicarboxylate on Cytochrome $P_{450}$ 1A1 and 2B1 and ${CCl_4}-Induced$ Hepatotoxicity in Rat Liver (Biphenyl Dimethyl Dicarboxylate가 간내 Cytochrome $P_{450}$ 1A1과 2Bl 및 $CCl_4$ 유도 간독성에 미치는 영향)

  • 김순선;오현영;김학림;양지선;김동섭;신윤용;최기환
    • YAKHAK HOEJI
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    • v.43 no.6
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    • pp.827-833
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    • 1999
  • In this study, we have investigated the effect of Biphenyl Dimethyl Dicarboxylate (DDB), a synthetic analogue of Schizandrin C isolated from Schizandrae Fructus on cytochrome $P_450$ lAl and 2Bl, and the protective mechanism against $CCl_4-induced$ hepatotoxicity in rat liver. After DDB was administered into male rats for different periods of time (1~7 days) and with different doses (25, 50, 100 and 200 mg/kg), mRNA levels of CYPlAl were measured by polymearse chain reaction (PCR) and assayed the activities of CYPlAl specific ethoxyresorufin-O-dealkylase (EROD) and CYP2Bl specific benzyloxyresorufin-O-dealkylase (BROD). DDB treatment resulted in increase in CYP2Bl mRNA level and BROD activity, whereas there was no change in CYPlAl mRNA level and EROD activity. This effect of DDB was time-and dose-dependent and reached maximal level by 3 day and 200 mg/kg treatment. In addition, rats were pre-treated with DDB at doses of 25, 50 or 100 mg/kg daily for 4 days, 3-hr after final treatment on the 4th day, $CCl_4$ 0.3ml/kg was intraperitonially injected into the rats to examine the effect of DDB on $CCl_4-induced$ hepatic injury. Serum levels of ALT and AST were determined and histopathological examination was done in rat liver. Furthermore, we have measured hepatic microsomal malondialdehyde(MDA) level, a parameter of lipid peroxidation. Based on serum ALT level and lipid peroxidation, pretreatment of DDB, 50 mg/kg appeared the most protective effect against $CCl_4-induced$ heapatotoxity. These results indicate that DDB stimulates CYP2Bl mRNA level and BROD activity in time and dose dependent manner and suggest that protective effect of DDB on $CCl_4-induced$ hepatotoxicity may be mediated through free radical scavenging.

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Effect of Kamisamul-tang on Hypertension and Free Radical (가미사물탕(加味四物湯)이 고혈압 병태 모델과 활성산소에 미치는 영향)

  • Song, Nak-Kun;Koo, Young-Sun;Kim, Dong-Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1485-1496
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    • 2006
  • Various kinds of related parameters on hypertension such as anti-oxygen effect, ACE, weight of body, hwart and kidney, blood pressure, heartbeat rates, contents of aldosterone, catecholamine, change rates, of plasma constituents, uric acid, BUN, creatinine were determined to verify the effects on hypertension by Kamisamul-tang (KSMT). And the results are concluded as follows. KSMT did not show any cytotoxicity at the range of concentration (1-250 ${\mu}g/m{\ell}$) on the human fibroblast cell (hFCs). KSMT decreased the production of reactive oxygen species (ROS) and DPPH generation depending on the concentration. KSMT significantly inhibited angiotensin converting enzyme(ACE) activity depending on the concentration compared with control. KSMT maintained body weight of body, heat and kidney nearly normal group in hypertensive rat induced by DOCA-salt. KSMT significantly blood pressure and heart beat rate compared with control in hypertensive rat induced by DOCA-salt. KSMT significantly decreased aldosterone, dopamine, norepineph- rine, epinephrine compared with control in hypertensive rat induced by DOCA-salt. KSMT significantly decreased the level of potassium and cloride compared with control wheareas increased that of calcium significantly in hypertensive rat induced by DOCA-salt. KSMT significantly decreased the level of uric acid and BUN compared with control in hypertensive rat induced by DOCA-salt. It is verified experimentally tat Kamisamultang(KMST) which has been used broadly as a clinical therapeutics in oriental medicine is effective for anti-hypertension mechanism. And it could be applied to develope the reliable prescriptions for anti-hypertension in the future.

Antioxidant, Cytotoxicity and Cytoprotective Potential of Extracts of Grewia Flava and Grewia Bicolor Berries

  • Masisi, Kabo;Masamba, Riach;Lashani, Keletso;Li, Chunyang;Kwape, Tebogo E.;Gaobotse, Goabaone
    • Journal of Pharmacopuncture
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    • v.24 no.1
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    • pp.24-31
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    • 2021
  • Objectives: Accumulation of cellular reactive oxygen species (ROS) leads to oxidative stress. Increased production of ROS, such as superoxide anion, or a deficiency in their clearance by antioxidant defences, mediates cellular pathology. Grewia Spp fruits are a source of bioactive compounds and have notable antioxidant activity. Although the antioxidant capacity of Grewia Spp has been studied, there is very limited evidence that links the antioxidant activities of Grewia bicolor and Grewia flava to the inhibition of free radical formation associated with damage in biological systems. Methods: This study evaluated the protective effects of Grewia bicolor and Grewia flava extracts against free radical-induced oxidative stress and the resulting cytotoxicity effect using HeLa cells. Antioxidant properties determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and total phenolic content (TPC) assays showed significantly higher (p < 0.05) antioxidant activity in Grewia flava (ethanol extract) than Grewia flava (water extract) and Grewia bicolor (ethanol and water extracts). Results: Using 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide or MTT assay, cytotoxicity results showed that extracts of Grewia bicolor and Grewia flava were less toxic to HeLa cells at tested concentrations compared to the untreated control. This confirmed the low toxicity of these edible fruits at the tested concentrations in HeLa cells. Furthermore, hydrogen peroxide (H2O2)-induced cell loss was effectively reduced by pre-incubating HeLa cells with Grewia bicolor and Grewia flava extracts, with Grewia flava (ethanol extract) revealing better protection. Conclusion: The effect was speculated to be associated with the higher antioxidant activity of Grewia flava (ethanol extract). Additional studies will warrant confirmation of the mechanism of action of such effects.

Formation and Inhibition of Cholesterol Oxidation Products (COPs) in Foods; An Overview (식품 내 콜레스테롤 산화 생성물(COPs)의 생성 및 억제; 개요)

  • Joo-Shin Kim
    • Journal of the Korean Applied Science and Technology
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    • v.40 no.5
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    • pp.1163-1175
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    • 2023
  • Cholesterol is prone to oxidation, which results in the formation of cholesterol oxidation products (COPs). This occurs because it is a monounsaturated lipid with a double bond on C-5 position. Cholesterol in foods is mostly non-enzymatically oxidized by reactive oxygen species (ROS)-mediated auto-oxidative reaction. The COPs are found in many common foods of animal-origin and are formed during their manufacture process. The formation of COPs is mainly related to the temperature and the heating time the food is processed, storage condition, light exposure and level of activator present such as free radical. The level of COPs in processed foods could reach up to 1-10 % of the total cholesterol depending on the foods. The most predominant COPs in foods including meat, eggs, dairy products as well as other foods of animal origin were 7-ketocholesterol, 7 α-hydroxycholesterol (7α-OH), 7β-hydroxycholesterol (7β-OH), 5,6α-epoxycholesterol (5,6α-EP), 5,6β-epoxycholesterol (5,6β-EP), 25-hydoxycholesterol (25-OH), 20-hydroxycholesterol (20-OH) and cholestanetriol (triol). They are mainly formed non-enzymatically by cholesterol autoxidation. The COPs are known to be potentially more hazardous to human health than pure cholesterol. The procedure to block cholesterol oxidation in foods should be similar to that of lipid oxidation inhibition since both cholesterol and lipid oxidation go through the same free radical mechanism. The formation of COPs in foods can be stopped by decreasing heating time and temperature, controlling storage condition as well as adding antioxidants into food products. This review aims to present, discuss and respond to articles and studies published on the topics of the formation and inhibition of COPs in foods and key factors that might affect cholesterol oxidation. This review may be used as a basic guide to control the formation of COPs in the food industry.

Assessment of antinociceptive property of Cynara scolymus L. and possible mechanism of action in the formalin and writhing models of nociception in mice

  • Pegah Yaghooti;Samad Alimoahmmadi
    • The Korean Journal of Pain
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    • v.37 no.3
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    • pp.218-232
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    • 2024
  • Background: Cynara scolymus has bioactive constituents and has been used for therapeutic actions. The present study was undertaken to investigate the mechanisms underlying pain-relieving effects of the hydroethanolic extract of C. scolymus (HECS). Methods: The antinociceptive activity of HECS was assessed through formalin and acetic acid-induced writhing tests at doses of 50, 100 and 200 mg/kg intraperitoneally. Additionally, naloxone (non-selective opioid receptors antagonist, 2 mg/kg), atropine (non-selective muscarinic receptors antagonist, 1 mg/kg), chlorpheniramine (histamine H1-receptor antagonist, 20 mg/kg), cimetidine (histamine H2-receptor antagonist, 12.5 mg/kg), flumazenil (GABAA/BDZ receptor antagonist, 5 mg/kg) and cyproheptadine (serotonin receptor antagonist, 4 mg/kg) were used to determine the systems implicated in HECS-induced analgesia. Impact of HECS on locomotor activity was executed by open-field test. Determination of total phenolic content (TPC) and total flavonoid content (TFC) was done. Evaluation of antioxidant activity was conducted employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Results: HECS (50, 100 and 200 mg/kg) significantly indicated dose dependent antinociceptive activity against pain-related behavior induced by formalin and acetic acid (P < 0.001). Pretreatment with naloxone, atropine and flumazenil significantly reversed HECS-induced analgesia. Antinociceptive effect of HECS remained unaffected by chlorpheniramine, cimetidine and cyproheptadine. Locomotor activity was not affected by HECS. TPC and TFC of HECS were 59.49 ± 5.57 mgGAE/g dry extract and 93.39 ± 17.16 mgRE/g dry extract, respectively. DPPH free radical scavenging activity (IC50) of HECS was 161.32 ± 0.03 ㎍/mL. Conclusions: HECS possesses antinociceptive activity which is mediated via opioidergic, cholinergic and GABAergic pathways.

Effects of Aralia elata Water Extracts on Activities of Hepatic Oxygen Free Radical Generating and Scavenging Enzymes in Streptozotocin-Induced Diabetic Rats (두릅열수추출물이 당뇨유발 흰쥐의 간조직 중 유해 활성산소 대사효소계 활성에 미치는 영향)

  • 김명주;조수열;이미경;신경희
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.4
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    • pp.653-658
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    • 2004
  • Oxidative stress is currently suggested as a mechanism underyling diabetes. Accordingly, the present study was designed to evaluate the effect of Aralia elate water extracts (AEW) on activities of hepatic oxygen free radical generating and scavenging enzymes in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats divided into nondiabetic group, diabetic group, and diabetic-AEW supplemented group. The extract was supplemented in 1.14% of raw Aralia elata/kg diet for 7 weeks. Diabetes was induced by injecting STZ (55 mg/kg BW, ip) once 2 weeks before sacrifying. The hepatic cytochrome P-450 content, xanthine oxidase and aminopyrine N-demethylase activities were significantly lowered in the diabetic group compared to the nondiabetic group. Whereas, the activities of aniline hydroxylase and oxygen free radical scavenging enzymes, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione S-transferase, were significantly higher in the diabetic group than in the nondiabetic group. However, the supplementation of AEW normalized these enzyme activities in STZ-induced diabetic rats. When the AEW was supplemented with the diabetic rats, hepatic glutathione content was markedly elevated as well as lipid peroxide level was significantly lowered compared to those of the diabetic group. Thus, these results suggested that AEW supplement enhanced the activities of oxygen species metabolizing enzymes in STZ-induced diabetic rats.

Oxidation and Surface Functional Group Analyses under Ozone Treatment of Carbon Black (오존처리에 의한 카본 블랙의 산화와 표면 작용기 분석)

  • Yang, Se-In;Kim, Ki-Yeo;Rhyoo, Hae-Yoon;Cho, Sang-Je;Yoon, Kwang-Eui
    • Elastomers and Composites
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    • v.40 no.3
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    • pp.188-195
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    • 2005
  • Chemical and physical changes and the contents of functional groups in the carbon black surface after the ozone treatment was investigated using elemental analysis, pH, tint strength, DBP, $N_2SA$, IA, and acid-base reaction. As the treatment time was increased, surface structure, particle size and surface area of carbon black did not change, while surface oxygen contents increased, and pH decreased and then saturated after $1{\sim}2$ hour. The contents of carboxylic, lactone, hydroxyl, and carbonyl groups were analyzed with four bases such as $NaHCO_3,\;Na_2CO_3,\;NaOH$, and $NaOC_2H_5$. Before oxidation, the carbonyl group was dominantly present on the surface, but by increasing the treatment time, the contents of the carboxylic and carbonyl groups increased to a saturated level after $1{\sim}2$ hour. Before and after the oxidation, the lactone and hydroxyl groups were nearly absent. These results showed that the reaction mechanism of carbon black and ozone is similar to that of ethylene and ozone. Weight of oxidized carbon black was increased after treating AIBN, while free radical was slightly decreased by ESR analysis. When carbon black was treated with organic compounds containing mercapto- groups, the results of ESR showed that free radical peak intensity was almost diminished compared to original carbon black.

Antioxidant and Whitening Effects of Sorbus commixta HEDL Cortex Extract (정공피 추출물의 항산화 활성 및 미백효과에 관한 연구)

  • Kim, Tae-Hyuk;You, Jin-Kyoun;Kim, Jeong-Mi;Baek, Jong-Mi;Kim, Hyun-Sook;Park, Jeong-Hae;Choe, Myeon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.10
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    • pp.1418-1424
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    • 2010
  • This study was performed to assess the antioxidant activities and whitening effects of Sorbus commixta HEDL cortex on melanin synthesis. The whitening effects of Sorbus commixta HEDL cortex water extracts were examined by in vitro mushroom tyrosinase assay and B16BL6 melanoma cells. We assessed inhibitory effects of Sorbus commixta HEDL cortex water extracts on expression of melanogenic enzyme proteins including tyrosinase, tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2 (TRP-2) in B16BL6 cells. Inhibitory effects of Sorbus commixta HEDL cortex onto free radical generation were determined by measuring DPPH and hydroxyl radical scavenging activities. Our results indicated that Sorbus commixta HEDL cortex water extracts effectively inhibited free radical generation. In DPPH radical scavenging activity, Sorbus commixta HEDL cortex water extracts had a potent anti-oxidant activity in a dose-dependent manner. They significantly inhibited tyrosinase activity in vitro and in B16BL6 melanoma cells. Also, Sorbus commixta HEDL cortex suppressed the expression of tyrosinase, TRP-1 and TRP-2 in B16BL6 melanoma cells. These results show that Sorbus commixta HEDL cortex inhibited melanin production on the melanogenesis. The underlying mechanism of Sorbus commixta HEDL cortex on whitening activity may be due to the inhibition of tyrosinase activity and tyrosinase, TRP-1, TRP-2 expression. We suggest that Sorbus commixta HEDL cortex may be contain new natural active ingredients for antioxidant and whitening cosmetics.

Action Mechanism of Anticonvulsive Effect of Nelumbo Nucifera in Pentylenetetrazole-induced Animal Models (펜틸렌테트라졸로 유도된 실험동물에서 연자육 추출물의 항경련 작용기전)

  • Kim, Sung-Hoon;Choi, Jong-Won
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.4
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    • pp.614-619
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    • 2011
  • Nelumbo nucifera(NN) is a oriental medicinal herb which has been used traditionally for the treatment of antidiarrhea, sedative action and various brain diseases including convulsion and epilepsy. In order to examine the mechanism of anticonvulsive effect, we treated the methanol extract of NN(100, 200 mg/kg, P.0) to the sleeping time and pentylenetetrazole(PTZ)-induced convulsive mice. The methanol extract of NN prolonged sleep time by pentobarbital. Methanol extracts of NN were not effected the concentration of GABA and GABA-T activity in the brain of PTZ-induced mice. Methanol extracts of NN significantly inhibited the convulsion state as well as the level of lipid peroxidation in the brain. The butanol and dichloromethane fraction of methanol extracts among the others effectively inhibited in vitro lipid peroxidation dose dependently($5.0{\times}10^{-6}\sim2.0{\times}10^{-5}\;g/ml$). These results suggest that the anticonvulsive effect of NN is possibly due to the antioxidative effects of the free radical formation at brain for the PTZ-induced convulsion if it were by due to generating system.

The Role of Nitric Oxide in Menadione-Induced Cytotoxicity in Rat Platelets (Menadione에 의한 흰쥐 혈소판 세포독성에서 nitric oxide의 역할)

  • 승상애;김대병;윤여표;정진호
    • Toxicological Research
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    • v.11 no.2
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    • pp.303-308
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    • 1995
  • Nitric oxide, a physiological transmitter, is reported to mediate cellular injury in various tissues. Its reactivity to free radical is believed to be one of the reasons for its involvement in cytotoxicity. Menadione, a representative quinone, is cytotoxic to several cell systems including isolated hepatocyte, endothelial cell and red blood cells. Its toxic mechanism is related to oxidative stress, mediated by toxic free radicals. Our previous studies demonstrated that menadione induced cell lysis and increase of oxygen consumption in platelets. It has been reported that platelets have nitric oxide producing enzyme, nitric oxide synthase. Thus, we have investigated to manifest the role of nitric oxide.in menadione-induced cytotoxicity in rat platelets. Menadione induced cytotoxicity in platelets was unaffected by $N^G$-nitro-arginine methyl ester (L-NAME), selective and competitive inhibitor of nitric oxide synthase. We also invesitgated the role of extracellular nitric oxide in menadione-induced cytotoxicity of platelets by addition with sodium nitroprusside (SNP). SNP did not affect platelet cytotoxicity by menadione. These results suggested that nitric oxide which was generated endogeneously or exogeneously might have a negligible role in menadione-induced cytotoxicity in rat platelets.

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