nghiên cứu sự biến đổi một số chỉ số chống oxy hóa ở người tiếp xúc nghề nghiệp với chì vô cơ, tác dụng bảo vệ của sâm ngọc linh trên động vật thực nghiệm bản tóm tắt tiếng anh

26 631 0
nghiên cứu sự biến đổi một số chỉ số chống oxy hóa ở người tiếp xúc nghề nghiệp với chì vô cơ, tác dụng bảo vệ của sâm ngọc linh trên động vật thực nghiệm bản tóm tắt tiếng anh

Đang tải... (xem toàn văn)

Tài liệu hạn chế xem trước, để xem đầy đủ mời bạn chọn Tải xuống

Thông tin tài liệu

LIST OF LETTERS, SYMBOLS HAVE ABBREVIATED IN THESIS TT Abbreviation All letters 1. ADN Acid desoxyribonucleic 2. ALA Acid aminolevulinic 3. ALAD Acid aminolevulinic dehydratase 4. ALT Alanin transaminase 5. AST Aspartat transaminase 6. GGT Gamma glutamyl transferase 7. GPx Glutathion peroxidase 8. GR Glutathion reductase 9. LO • Gốc alkoxyl 10. LOO • Gốc peroxyl 11. LPO Lipid hydroperoxides 12. MCH Mean corpuscular volume 13. MCHC Mean corpuscular hemoglobin concenrtration 14. MDA Malonyl dialdehyd 15. ppm Parts per million 16. G Group 17. ROS Reactive oxygen species 18. TAS Total antioxydant status 2 INTRODUCTION When infiltrating into body, lead causes a number of diversified and complicated injuries on most organs and organizations. The mechanism of causing diseases of lead is inhibiting and linking with enzymes, biological substances containing -SH group but not satisfactorily explaining the systematically lead- induced injuries. Some studies shown that lead entering into the body can stimulate the generation of free radicals and reduce the function of the system against free radicals. To clarify this matter, it is necessary to evaluate changes of antioxidant enzymes in the body. Panax vietnamensis biomass is believed to have capacity of preventing oxidation, protecting the body from oxidative stress. The application and assessment of the protection effectiveness of Panax vietnamensis biomass for objects exposing to lead is a new issue which has not been studied in reality. Based on that fact, we carry out the theme “Study the change of some oxidation indexes of people occupationally exposing to inorganic lead, the protective effects of biomass Panax vietnamensis on experimental animals”. 1. Objectives: - Specify the change of some antioxidant indexes and blood biochemistry of people occupationally exposing to inorganic lead and experimental animals. - Assess the protective effects of Panax vietnamensis biomass on animals infected semi-chronic with lead acetate. 2. Necessity: Lead is an irreplaceable raw material in many industries. The number of people exposing to lead not only reduces but also tends to increase despite the fact that lead triggers to several adverse effects on human’s health. When entering into the body, lead can cause occupational exposure and oxidative stress. Nowadays, specific treatment drugs are used to treat lead poisoning but their effects are not as expected especially in chronic poisoning. Panax vietnamensis biomass is a preparation having 3 antioxidant and protective effects on the body. It can reduce harms of lead causing to the body. From this fact, we conducted to study this theme. 3. New contributions of the thesis: Lead is harmful to the body, causing oxidative stress which leads to the alteration of antioxidant indexes. The thesis studied quite comprehensively the antioxidant indexes of workers directly exposing to inorganic lead and on experimental animals. The thesis assessed the protective effects of Panax vietnamensis biomass on animals semichronic poisoned with lead acetate. By dint of the research results, factories, enterprises using lead in production enhance measures to protect heath of labors as well as study more to choose Panax vietnamensis biomass to protect workers occupationally exposing to lead. 4. Arrangement of the thesis: The thesis includes 137 pages consisting of 2 pages of introduction, 38 pages of general view, 20 pages of research objects and methods, 41 pages of research results, 33 pages of discussion, 2 pages of conclusion, 1 page of recommendation. The thesis has 37 tables, 21 charts, 5 diagrams, and 161 references in which 27 in Vietnamese and 137 in English. CHAPTER 1 - GENERAL VIEW 1.1. Free radicals and system against the free radicals of the body 1.1.1. Definition of free radicals and types of Reactive Oxygen Species (ROS) Free radicals are atoms or group of atoms whose outer layer contains unpaired electrons (single electrons). Free radicals are frequently unstable in both energy and kinematics and tend to reach to very short stability and longevity, strong reactivity. ROS are free radicals, active ions, and molecules containing oxygen atoms and are capable of generating free radicals or activated by free radicals. 1.1.2. Oxidative stress 4 Oxidative stress is an imbalance between the formation of reactive oxygen species and the antioxidant systems. Oxidative stress may be resulted from the decline of the antioxidant system, increasing formation of reactive oxygen species and the lack of ability to repair injuries caused by oxidation in the body. 1.1.3. The formation process of free radicals. The free radicals in the body is created from cellular respiration chain, radioactive agents, inflammatory syndrome, the phenomenon of ischemia - reperfusion, xenobiotic agents and some other factors. Xenobiotic substances including lead when entering into the body will be converted and xenobiotic structure significantly altered, they can add more -OH,-NH2,-SH,-COOH groups to form water-soluble substances and continue connecting with substances, excreting from the body; at the same time generating ROS such as • 2 O , 1 O 2, etc which have high toxicity causing oxidative stress. The antioxidants in the body such as SOD, catalase, protein SH groups, ceruloplasmin, etc in erythrocytes and liver are very sensitive to the xenobiotic. 1.1.4. Antioxidant system in the body. 1.1.4.1. Ezymatic antioxidant system. - Superoxid dismutase (SOD, EC 1.15.1.1) is an antioxidant enzyme containing metal of oxidoreductase type and it catalyzes the reaction to convert superoxid to O 2 and H 2 O 2 : 2 • 2 O + 2H + → SOD H 2 O 2 + O 2 The higher activity SOD has, the less activity O 2 • has. SOD SOD is an very basic antioxidant that lowers the concentration of precursor • 2 O from which all other reactive oxygen species are produced. - Catalase (CAT, EC 1.15.1.1) is an enzyme catalyxing the reaction of H 2 O 2 decompostion H 2 O 2  → Catalase H 2 O + ½ O 2 5 - Peroxidase (EC 1.11.1.7) is a group of enzyems catalyzing redox reaction belong to oxidoreductase catalyzing the following reaction. AH 2 + H 2 O 2  → peroxidase A + 2H 2 O - Glutathion peroxidase (GPx) (E C.1.11.1.9) is an enzyme catalyzing reactions to remove peroxides which activate in the tissues and erythrocyte when the concentration of H2O2 is low. GPx ROOH + 2GSH GSSG + ROH + H 2 O 1.1.4.2. Non-enzymatic antioxidant system It consists of three main groups: group of polyphenols, iron and copper ligands and thiols. The gruops can exist both inside and outside cells. This system support for te enzymatic antioxidant system. - Total antioxidant status (TAS) is the total antioxidant status of plasma basing on the ability of inhibiting and combating the oxidants of antioxidants including all the antioxidants in the body wich include a lot of protection systems to prevent from the adverse effects of free radicals and peroxide phenomenon for the body. 1.2. The Mechanism of effect, capacity of generating free radicals, inhibiting antioxidant system of inorganic lead 1.2.1. Mechanisms of common effects Lead entering into the body will inhibit and connect selectively with enzyme system, biomolecular having -SH group and cause several important biochemical disorders of cells. 1.2.2. Mechanism of generating free radicals, inhibiting antioxidant system of inorganic lead Inorganic Lead induces to oxidative stress by two opposing mechanisms closely linking to each other: stimulating the formation of free radicals and reducing the antioxidant ability of the body. - Stimulating the generation of free radicals: free radicals are formed from four main sources such as (1) the enolization and oxidation process of aminolevulinic acid (ALA), (2) the self- 6 oxidation of oxyhemoglobin, (3) the enhancement of activity of oxidative enzymes, (4) the oxidation of nitric oxide by free radicals. - Inhibiting the antioxidant system: Lead associates with -SH groups to reduce level of GSH, GR, G6PD activity and GSH/GSSH ratio. Lead reduces the absorption of microquantity elements such as selenium, Cu, Zn, therefore reducing the activity of antioxidant enzymes such as GPx, SOD, CAT and increasing reactivity of the membranes to oxidative attacks. 1.3. Antioxidant effects of biomass Panax vietnamensis 1.3.1. Chemical composition Panax vietnamensis biomass consists of main chemical ingredients such as saponin whose total content is 2.01%. In which, the content of ginsennosids such as Rg1, Rb1, Rg1 is 0.31%, 0.36%, 0.15% respectively. 1.3.2. Antioxidant effects Total saponin and active element MR-2 in SNL antioxidant have antioxidant effects. Ginseng extracts can inhibit the formation of OH • radicals from Fenton reaction by the mechanism of complexion with metal ions as well as directly cleanup OH • radicals. They have antioxidant effects in both the oil and water environment and are able to participate in all stages of the POL process. Some authors believed that antioxidant effects of SNL are by dint of the mineral components of ginseng. CHAPTER 2- RESEARCH OBJECTS AND METHODS 2.1. Research objects 2.1.1. Study labor environment Study on characteristics of microclimate and lead level in the air in labor environment. 2.1.2. Study on humans - Objects: 165 workers working in primary detonating explosives (Zx factory); battery assembly workshop, plate electrode workshop (Vinh Phu Battery Joint Stock Company) directly exposing to lead, are divided into 2 groups: 7 + Group I (55 workers) has blood lead level ≤ 10 µg/dL + Group II (110 workers) has blood lead level > 10 µg/dL. + Group II is divided into 2 small groups: Group IIA (86 workers): blood lead level from 10 µg/dL to < 40 µg/dL and group IIB (24 workers): blood lead level ≥ 40 µg/dL. - Criteria to choose: + Time to work in the environment directly exposing to lead is ≥ 5 năm, and continuous. Not expose to other toxic elements. And participate in the study voluntarily. + Exclusion criteria: acute exacerbations of chronic diseases, malignant diseases, diabetes mellitus, hypertension, kidney diseases, acute and chronic hepatitis, liver failure and autoimmune disease. - Choose all workers in the criteria and not in exclusion criteria into the research. 2.1.3. Study on animals * Experimental animals: 360 male white house-mice, 20 - 25 gram, divided into 3 lots. - Control lot (108 mice) (lot 1). - Lot infected lead acetate (108 mice) (lot 2). - Lot infected lead acetate and drinking/with SNLSK to protect (108 mice) (lot 3). - 36 mice were killed and taken blood to experiment immediately prior to testing. * Research materials. Lead acetate solution is provided by Division of Technical Equipment, Vietnam Military Medical Academy (manufactured by Lucheng Qinda plastic injection Factory- China). Panax vietnamensis biomass is newly manufactured and provided by the Center for Research and Application of Military Medicine, Vietnam Military Medical Academy. Research tools are full enough for the experiment. 2.2. Research methods. 2.2.1. Research methods of labor environment. Survey microclimate and lead dust concentration in labor environment. 8 2.2.2. Research methods on workers - Research design: descriptive and cross-sectional - Research targets and techniques. + Test lead concentration in blood + Test peripheral blood formula + Test blood biochemistry indexes + Identify content of free –SH group in blood, activity of plasma peroxidase, erythrocyte superoxide dismutase (SOD), activity of erythrocyte glutathion peroxidase (GPx), plasma malondialdehyde (MDA), plasma total antioxidant status (TAS). 2.2.3. Research methods on animals. Research design: experimental, have intervention * Mix lead acetate and Panax vietnamenis biomass: Mix 2,592g (2.592mg) of lead acetate into 1,296L (1.296mL) of distilled water, obtain lead acetate solution. Mix 24,30g (24.300mg) of Panax vietnamenis biomass into 0,324L (324mL) of distilled water, obtain Panax vietnamenis biomass solution. * Toxic method: Semichronic toxic method under toxic model of El-Sayed I. H, Lotfy. M et al (2006); Flora G, Gupta D et al (2013) - Lot 1 (n = 108): drink 0,2mL of distilled water in mornings every day, continuous in 15 days, 30 days and 45 days. - Lot 2 (n = 108): drink 0,2mL of lead acetate solution (20 mg/kg/day) in mornings every day, continuous in 15 days, 30 days and 45 days. - Lot 3 (n = 108): drink 0,1mL of Panax vietnamensis biomass solution (375 mg/kg/day). After drinking SNLSK for one hour, mice are drunk 0,2mL of lead acetate solution (20 mg/kg/day), continuous in 15 days, 30 days and 45 days. * Method of blood drawn for testing: Mice are killed at the time of experiment and blood is taken at two eye sockets. * Prior to the implementation of experiment: (36 mice). - 12 mice are randomly selected, taken blood and divided into 2 parts to test blood formula and blood lead level. 9 - 12 next mice are randomly in the remainder, taken blood and divided into 2 parts to test the activity of SOD, erythrocyte GPx and TAS, activity of peroxidase, plasma MDA, -SH. - 12 remaining mice are taken blood to test biochemistry index. * After the implementation of experiment: (324 mice). - At the time of 15 days, 30 days and 45 days after the implementation of experiment, 108 mice (each lot: 36 mice) are randomly selected, killed and taken blood for the experiment. * Research targets and techniques: as on humans. 2.3. Data processing The data is processed by medical statistical methods and used softwares such as EpiInfo 2005 (Version 3.3.2), EpiCalc 2000. 2.4. Ethnic issues in the research. Ensure medical ethnics in the research. CHAPTER 3 RESULT OF RESEARCH 3.1. Result of research on human. 3.1.1. The mean blood lead level in the research groups. 10 Group Content Group I (n=55) ( X ±SD) Group II (n=110) ( X ±SD) Group II Group IIA (n=86) ( X ±SD) Group IIB (n=24) ( X ±SD) blood lead level (µg/dL) 4,26±2,28 36,54±18,36 23,82±7,54 57,66±9,73 Blood lead level in group II, IIB have considerable change. 3.1.2.The result of test of SOD, GPx, peroxidase, -SH, MDA, TAS in the research groups. Table 3.7. The change of some antioxidant index in group I, II Group Content Group I (n=55) ( X ±SD) Group II (n=110)( X ±SD) p SOD (U/g Hb) 1212.87±180.70 1578.26±180.65 p<0.001 GPx (U/g Hb) 64.46±8.57 54.29±7.82 p<0.001 Peroxidase (µg/mg) 0.019±0.006 0.021±0.008 p>0.05 - SH (mmol/mg) 0.685±0.092 0.461±0.120 p<0.001 MDA (µmol/L) 3.19±0.42 4.01±0.49 p<0.001 TAS (mmol/L) 1.58±0.22 1.42±0.21 p<0.001 Table 3.11. The correlation of SOD, GPx, peroxidase, MDA, TAS with blood lead level in group II Content r p Linear equation SOD (U/gHb) BLL (µg/dL) 0.45 <0.05 y = 5.282 x + 1197 GPx (U/gHb) BLL (µg/dL) -0.49 <0.01 y = -0.339 x + 58.31 [...]... 3.51±0.44 3.54±0.41 L3 1.52±0.14 2.72±0.58 2.58±0.55 2.56±0.46 p21 . transferase 7. GPx Glutathion peroxidase 8. GR Glutathion reductase 9. LO • Gốc alkoxyl 10. LOO • Gốc peroxyl 11. LPO Lipid hydroperoxides 12. MCH Mean corpuscular volume 13. MCHC Mean corpuscular. MDA Malonyl dialdehyd 15. ppm Parts per million 16. G Group 17. ROS Reactive oxygen species 18. TAS Total antioxydant status 2 INTRODUCTION When infiltrating into body, lead causes a number. containing oxygen atoms and are capable of generating free radicals or activated by free radicals. 1.1.2. Oxidative stress 4 Oxidative stress is an imbalance between the formation of reactive oxygen

Ngày đăng: 03/10/2014, 11:02

Từ khóa liên quan

Tài liệu cùng người dùng

  • Đang cập nhật ...

Tài liệu liên quan