Gotowa bibliografia na temat „Xanthines – therapeutic use”

Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach.The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety).Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD.

This article aims to critically review the evidence on the available therapeutic strategies for the treatment of hyperuricemia. For this reason, several papers were reviewed. Xanthine oxidase inhibitors are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia, while the efficacy of uricosuric agents is strongly modulated by pharmacogenetics. Emergent drugs (lesinurad, peglotidase) were found to be more effective for the acute management of refractory hyperuricemia, but their use is supported by a relatively small number of clinical trials so that further well-designed clinical research is needed to deepen their efficacy and safety profile.

This article aims to critically review the evidence on the available therapeutic strategies for the treatment of hyperuricemia. For this reason, several papers were reviewed. Xanthine oxidase inhibitors are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia, while the efficacy of uricosuric agents is strongly modulated by pharmacogenetics. Emergent drugs (lesinurad, peglotidase) were found to be more effective for the acute management of refractory hyperuricemia, but their use is supported by a relatively small number of clinical trials so that further well-designed clinical research is needed to deepen their efficacy and safety profile.

Gout is arthritis caused due to Monosodium urate (MSU) crystals deposition occurring particularly in patients with associated comorbidities limiting the use of conventional therapies. This study was planned to evaluate the therapeutic efficacy of urinile (a herbal drug) for the treatment of gouty arthritis. Allopurinol was used as standard drug (positive control). The study population of 250 volunteers (gouty arthritis patients) were divided into 2 groups as test and control group (n = 125 each). Gouty arthritis patients in test and control group were treated with 300 mg each of urinile and allopurinol, respectively. Clinical symptoms of all the study volunteers were recorded and serum uric acid was determined. Significant (p < 0.05) reduction in serum uric acid level toward normal was found in test group individuals. Clinical symptoms of gouty arthritis patients were also improved in test group compared to control group. Results showed that urinile has the potential to decrease serum uric acid level in gouty arthritis patients probably because of its antioxidant potential and xanthine oxidase inhibitory activity. It can be concluded that the tested herbal drug urinile is more potent in treating gouty arthritis patients and can be used as an effective alternative to the most commonly used allopathic drugs.

Background:Xanthine oxidase inhibitors (XOI) are commonly used as urate lowering therapy (ULT) for the treatment of gout. Allopurinol, the first-line treatment, demonstrates low response rate (< 40%), defined as serum urate (sUA) lowering effect below 6 mg/dL, in multiple large-scale clinical trials. As recommended in EULAR guidelines and other literatures, targeting sUA <5 mg/dL or even <4 mg/dL, provides a better opportunity to lower incidence of gout flare and resolution of tophi in gout patients. Febuxostat, a more potent XOI, has been classified as a second-line ULT agent due to increased cardiovascular risks in certain patient populations. For XOI intolerance and non-responders, replacing the agent with a potent URAT1 inhibitor or adding an URAT1 inhibitor onto a current treatment regimen provides opportunities to improve response rates in patients with refractory gout. AR882 is a uricosuric agent that blocks the reabsorption of uric acid in the apical side of renal tubule, hence increases excretion of uric acid into the urine. A phase 2a study has demonstrated the additive effects of AR882 in combination with allopurinol or febuxostat.Objectives:To evaluate the effect of AR882 alone or in combination with allopurinol or febuxostat on circulating levels and urinary excretion of hypoxanthine, xanthine and uric acid. Furthermore, to elucidate the contribution of each drug towards the combination effect in sUA lowering.Methods:Plasma, serum, and urine samples were collected from 17 patients with gout who received a once-daily dosing of AR882 50 mg, allopurinol 300 mg or febuxostat 40 mg, or in combination for one week in a phase 2a study. Samples were collected to measure hypoxanthine, xanthine and uric acid levels in plasma or serum and the amount of each excreted in the urine. Plasma Cmax and AUC and 24-hour urine excretion amount (mg) of hypoxanthine and xanthine were calculated by non-compartmental analysis method.Results:In monotherapy, AR882 demonstrated better sUA lowering effect (↓53%) compared to allopurinol (↓35%) or febuxostat (↓39%). Combination of AR882 and allopurinol lowered sUA by 66% while combination of AR882 and febuxostat lowered sUA by 71%. Based on the change of xanthine in plasma following combination treatments, it can be calculated that allopurinol contributed 28% of the urate lowering effect, whereas AR882 contributed 38% of the effect. Similarly, febuxostat contributed 33% of the urate lowering effect and AR882 contributed to about 36-38% of the effect when used in combination. The combination treatments significantly increased the response ratio for patients achieving sUA levels < 5 mg/dL, 4 mg/dL, and even 3 mg/dL. In the combination with allopurinol, 100%, 100%, 100%, and 44% patients achieved sUA < 6 mg/dL, < 5 mg/dL, 4 mg/dL, and 3 mg/dL, respectively. Similar results were seen with the combination of AR882 and febuxostat. Treatment with allopurinol or febuxostat alone resulted in 8 to 10-fold and 16-fold increases of xanthine exposure, respectively. The combination of AR882 and allopurinol or febuxostat showed approximately 5-8 fold or 13-fold increases in plasma xanthine, respectively. Treatment with allopurinol or febuxostat alone resulted in 2-3 fold increase in hypoxanthine exposure. Relative changes of hypoxanthine were not significantly different in the presence versus absence of AR882. Increased excretion of xanthine and hypoxanthine was also observed in urine. AR882 was well tolerated in gout patients, showing a similar safety profile to that observed in healthy volunteer studies.Conclusion:AR882 dose alone had no effect on plasma or urine hypoxanthine and xanthine levels. AR882 contributed to a greater portion of the serum urate lowering effects when used in combination with XO inhibitors, and with 100% of patients achieving levels below 4 mg/dL when combined with allopurinol. The use of AR882 in combination with XO inhibitors may provide an option for preventing flares as well as tophi reduction in advanced patients.Disclosure of Interests:Zancong Shen Employee of: arthrosi therapeutics, Chris Colton Employee of: Arthrosi therapeutics Inc, Rongzi Yan Employee of: Arthrosi therapeutics Inc, Elizabeth Polvent Employee of: Arthrosi therapeutics Inc, Vijay Hingorani Consultant of: Arthrosi therapeutics Inc, Shunqi Yan Employee of: Arthrosi therapeutics Inc, Li-Tain Yeh Employee of: Arthrosi therapeutics Inc.

Ceruloplasmin (CP), an important serum antioxidant, is a blue copper glycoprotein with ferroxidase and oxidase activities. Among other physiological actions, plasma CP was shown to protect isolated rat hearts and cultured P19 neurons exposed to oxidative stress conditions, raising the possibility of using this protein in the treatment of cardiac and neuronal diseases related to oxidative damage. However, since therapeutic applications of CP must be compatible with restrictions in the administration of blood derivatives to humans, there is a need to produce the protein by genetic engineering. To help in the choice of adequate expression systems, we undertook this study to determine if the carbohydrate moiety on the protein is essential for its functions. CP was completely deglycosylated using N-glycosidase F under nondenaturing conditions. Deglycosylated CP was found to retain most of the conformational, antioxidant, and enzymatic properties of the native protein in vitro. Moreover, both forms of the protein had similar cardioprotective and neuronoprotective effects against oxidative stress as evaluated with isolated rat hearts undergoing ischemia–reperfusion and with cultured P19 neurons exposed to xanthine – xanthine oxidase. The data thus indicate that the carbohydrate moiety of CP is not essential for its enzymatic and protective actions. Accordingly, even the use of expression systems that do not glycosylate mammalian proteins could provide a recombinant CP that retains its therapeutic potential.Key words: copperproteins, protein-linked carbohydrates, ischemia-reperfusion, isolated rat hearts, cultured P19 neurons.

Abstract Cardiovascular disease is the leading cause of disease / mortality worldwide. It is generally accepted that increased production of reactive oxygen species (ROS) has an important role in cardiovascular pathology, contributing to endothelial dysfunction and to the aggravation of atherosclerosis. Among all cardiovascular risk factors, diabetes mellitus is one of the most important. The worldwide prevalence of diabetes has increased rapidly even in developing countries, doubling the combined risk of cardiovascular events in patients with hypertension. In diabetes, increased reactive oxygen species (ROS) production leads to endothelial dysfunction, recognized by the presence of impaired vascular relaxation, increased vascular smooth muscle cells growth and hypertrophy, all together contributing to atherosclerotic plaque formation. On this basis, the vascular endothelium has emerged as a therapeutic target, with the aim to improve systemic metabolic state by improving vascular function. In this review we have focused on the most important sources of reactive oxygen species generated by vascular endothelium in diabetic patients (NADPH Oxidases, eNOS uncoupling, Xanthine oxidase). The importance of oxidative stress in mediating the vascular complications of diabetes is supported by studies showing that antioxidant therapy correct the vascular function in humans or in experimental models of diabetes. Therefore, understanding the physiological mechanisms involved in vascular disorders resulting from hyperglycemia is essential for the proper use of available therapeutic resources.

Background:According to modern concepts, rheumatoid arthritis (RA) refers to severe autoimmune rheumatic diseases. The activation of free radical oxidation processes is essential in the development of this disease [1]. Xanthine oxidoreductase is a significant reactive oxygen species source [2]. Despite the great advances in the treatment of rheumatoid arthritis (RA) associated with the introduction of innovative drugs and especially the improvement of the strategy for their use into clinical practice, glucocorticoids still remain an important component of RA pharmacotherapy in actual clinical practice.Objectives:to evaluate the changes in activities of xanthine oxidoreductase interconvertible forms (xanthine oxidase, ЕС 1.17.3.2 and xanthine dehydrogenase, ЕС 1.17.1.4) in lysed red blood cells of RA patients in relation with glucocorticoid treatment.Methods:47 RA patients with verified RA and 30 healthy controls were enrolled in the study. The diagnosis was verified using the 2010 ACR/EULAR criteria 2010. All patients have moderate DAS28 scores. RA patients were randomized into 2 groups comparable in gender, age and the principal clinical manifestations. Methylprednisolone (Metipred, Orion Corp.), average dose 30 mg/day, and betamethasone (Diprospan, Schering-Plough), single dose7 mg, were administered intramuscularly in the respective groups. Хanthine oxidase (XO) and xanthine dehydrogenase (XDG) activities were measured in lysed red blood cells by spectrophotometric method as previously described [3]. The changes of these enzymes activities were studied in RA patients before and after the injection of glucocorticoids. Statistical comparison tests were selected in according to common guidelines, differences were considered significant when p<0.05. Central tendencies were expressed as means±SEM.Results:Mean age of patients in methylprednisolone group was 41.8±1.05 years, and mean RA duration (± SEM) was 7.9±0.21 years. Mean age of patients in diprospan group was 40.9±1.07 years, and mean RA duration was 8.0±0.33 years. Significant decreases of XO activity and increase of XDG activity were observed in lysed red blood cells of RA patients just after the injection of each glucocorticoid drug. Changes of the enzymatic activities in lysed red blood cells were more pronounced in methylprednisolone group. However enzymatic activity did not reach the level of healthy controls. As described previously, decreased XO activity and increased XDG activity were observed in plasma of RA patients just after the injection of the average therapeutic doses of glucocorticoids, as well as in lysed lymphocytes just after the injection of methylprednisolone [4].Conclusion:Treatment with methylprednisolone and betamethasone can affect the balance of XO/XDG activity and increase the antioxidant potential of the blood. This effect can exert beneficial influence on autoimmune inflammation in RA.References:[1]Mateen S., et al. Increased reactive oxygen species formation and oxidative stress in rheumatoid arthritis. PLoS ONE 2016;11(4):e0152925.[2]Çimen M.Y., et al. Oxidant/antioxidant status of the erythrocytes from patients with rheumatoid arthritis. Clin Rheumatol 2000;19(4):275-277.[3]Zborovskaya I.A., et al. Influence of analgetics on plasma and lymphocytic activity of the purine metabolism enzymes in rheumatoid arthritis patients. Russian Journal of Pain 2018;3:47.[4]Mozgovaya E.E., et al. Xanthinoxidase and xanthine dehydrogenase activities in rheumatoid arthritis after glucocorticoid treatment. Osteoporosis International 2019;30(2):S433-434.Disclosure of Interests:None declared

Despite progress in understanding the pathophysiology of acute lung damage, currently approved treatment possibilities are limited to lung-protective ventilation, prone positioning, and supportive interventions. Various pharmacological approaches have also been tested, with neuromuscular blockers and corticosteroids considered as the most promising. However, inhibitors of phosphodiesterases (PDEs) also exert a broad spectrum of favorable effects potentially beneficial in acute lung damage. This article reviews pharmacological action and therapeutical potential of nonselective and selective PDE inhibitors and summarizes the results from available studies focused on the use of PDE inhibitors in animal models and clinical studies, including their adverse effects. The data suggest that xanthines as representatives of nonselective PDE inhibitors may reduce acute lung damage, and decrease mortality and length of hospital stay. Various (selective) PDE3, PDE4, and PDE5 inhibitors have also demonstrated stabilization of the pulmonary epithelial–endothelial barrier and reduction the sepsis- and inflammation-increased microvascular permeability, and suppression of the production of inflammatory mediators, which finally resulted in improved oxygenation and ventilatory parameters. However, the current lack of sufficient clinical evidence limits their recommendation for a broader use. A separate chapter focuses on involvement of cyclic adenosine monophosphate (cAMP) and PDE-related changes in its metabolism in association with coronavirus disease 2019 (COVID-19). The chapter illuminates perspectives of the use of PDE inhibitors as an add-on treatment based on actual experimental and clinical trials with preliminary data suggesting their potential benefit.

Thein vitromethods currently used to screen bioactive compounds focus on the use of a single model of oxidative stress. However, this simplistic view may lead to conflicting results. The aim of this study was to evaluate the antioxidant properties of two natural extracts (a mix of red wine polyphenols (RWPs) and epigallocatechin gallate (EGCG)) with three models of oxidative stress induced with hydrogen peroxide (H2O2), a mixture of hypoxanthine and xanthine oxidase (HX/XO), or streptozotocin (STZ) in RINm5F beta cells. We employed multiple approaches to validate their potential as therapeutic treatment options, including cell viability, reactive oxygen species production, and antioxidant enzymes expression. All three oxidative stresses induced a decrease in cell viability and an increase in apoptosis, whereas the level of ROS production was variable depending on the type of stress. The highest level of ROS was found for the HX/XO-induced stress, an increase that was reflected by higher expression antioxidant enzymes. Further, both antioxidant compounds presented beneficial effects during oxidative stress, but EGCG appeared to be a more efficient antioxidant. These data indicate that the efficiency of natural antioxidants is dependent on both the nature of the compound and the type of oxidative stress generated.

Helicobacter pylori infects more than half of the global population and causes gastric disorders. The increasing development of antibiotic resistance by the bacterium continues to limit treatment options. The identification and characterisation of novel therapeutic targets are necessary for successful future treatment of the infection. One potential target for therapeutic intervention is the gpt gene encoded by hp0735 (jhp0672) in H. pylori strain 26695 (J99). This gene produces a putative xanthine-guanine phosphoribosyltransferase (XGPRTase), an enzyme of the purine salvage synthesis pathway. This project employed theoretical, molecular and biochemical approaches to investigate features of H. pylori gpt and XGPRTase that will serve to ascertain their therapeutic potential. The production of a functional XGPRTase by H. pylori was investigated in cell-free extracts, and the kinetic parameters of this activity were compared to those of purified rXGPRTase enzyme. The three 6-oxopurine substrates were recognised by rXGPRTase and allosteric kinetics were observed for some substrates of the enzyme in cell-free extracts and for purified enzyme. These observations indicate complex regulation and an influence of cellular interactions on activity. Bioinformatics were employed to analyse XGPRTase phylogeny, and threading techniques used to build a structural model of XGPRTase. The enzyme is significantly divergent from the equivalent mammalian enzyme, and modelling identified specific features of the enzyme. Molecular approaches were utilised to analyse the essential role of gpt in H. pylori survival. These included insertional inactivation of the gpt in wild-type H. pylori strains and in mutants possessing a complementing copy of the gene present at the rdxA locus. No mutants were recovered with inactivated gpt possibly as a result of pleiotropic effects. Plasmid-mediated complementation was attempted employing IPTG-inducible shuttle vectors and did not yield any mutants. Further characterisation of H. pylori XGPRTase was performed by determining the effects of nucleotide monophosphates and purine analogues on enzyme activity. Inhibition by GMP was observed in all cases, however differences in the inhibition by other nucleotide monophosphates were found between cell-free extracts and the recombinant enzyme. Inhibition of rXGPRTase activity was observed by the purine analogue 6-mercaptopurine ribose, a compound that previously has been shown to inhibit H. pylori growth in culture.

Lam Rosanna Yen Yen.<br>Thesis submitted in: September 2004.<br>Thesis (M.Phil.)--Chinese University of Hong Kong, 2005.<br>Includes bibliographical references (leaves 142-154).<br>Abstracts in English and Chinese.<br>Abstract --- p.i<br>Chinese Abstract --- p.iii<br>Acknowledgements --- p.v<br>Table of Contents --- p.vi<br>List of Abbreviations --- p.xii<br>List of Figures --- p.xv<br>List of Tables --- p.xix<br>Chapter Chapter 1 --- Introduction --- p.1<br>Chapter 1.1 --- Reactive oxygen species --- p.1<br>Chapter 1.1.1 --- Intracellular sources of ROS --- p.1<br>Chapter 1.1.2 --- Extracellular sources of ROS --- p.2<br>Chapter 1.1.3 --- Superoxide anion radicals --- p.2<br>Chapter 1.1.4 --- Hydrogen peroxide --- p.3<br>Chapter 1.1.5 --- Hydroxyl radicals --- p.3<br>Chapter 1.1.6 --- Singlet oxygen --- p.4<br>Chapter 1.1.7 --- Peroxyl radicals and peroxides --- p.4<br>Chapter 1.1.8 --- Damage of cellular structures by ROS --- p.5<br>Chapter 1.2 --- Antioxidative defence in the body --- p.6<br>Chapter 1.2.1 --- Antioxidant proteins --- p.6<br>Chapter 1.2.2 --- Antioxidant enzymes --- p.6<br>Chapter 1.2.3 --- Antioxidant compounds --- p.7<br>Chapter 1.2.3.1 --- Vitamin E --- p.8<br>Chapter 1.2.3.2 --- Vitamin C --- p.9<br>Chapter 1.2.3.3 --- Glutathione --- p.9<br>Chapter 1.2.3.4 --- Urate --- p.9<br>Chapter 1.2.3.4.1 --- Purine metabolism --- p.10<br>Chapter 1.2.3.4.2 --- Xanthine oxidase --- p.12<br>Chapter 1.2.4 --- Oxidative stress and antioxidant defence mechanisms in RBC --- p.12<br>Chapter 1.2.5 --- Oxidative stress and antioxidant defence mechanisms in LDL --- p.16<br>Chapter 1.3 --- Human diseases originated from pro-oxidant conditions --- p.16<br>Chapter 1.3.1 --- Atherosclerosis --- p.17<br>Chapter 1.3.2 --- Ischemia /reperfusion injury --- p.17<br>Chapter 1.3.3 --- Glucose-6-phosphate dehydrogenase deficiency --- p.18<br>Chapter 1.3.4 --- DNA mutation --- p.18<br>Chapter 1.3.5 --- Other pro-oxidant state related diseases --- p.19<br>Chapter 1.4 --- Hyperuricemia and gout: diseases originated from an extreme antioxidant condition --- p.19<br>Chapter 1.4.1 --- Inhibition of XOD as a treatment method for hyperuricemia --- p.20<br>Chapter 1.4.2 --- Relationship between ROS injury and hyperuricemia --- p.22<br>Chapter 1.5 --- Antioxidants in human nutrition --- p.23<br>Chapter 1.6 --- Chinese medicinal therapeutics --- p.23<br>Chapter 1.6.1 --- Rhubarb --- p.25<br>Chapter 1.6.2 --- Aloe --- p.26<br>Chapter 1.6.3 --- Ginger --- p.27<br>Chapter 1.6.4 --- Objectives of the project --- p.30<br>Chapter 1.6.5 --- Strategies applied to achieve the objectives of the present project --- p.30<br>Chapter Chapter 2 --- Materials and methods --- p.31<br>Chapter 2.1 --- XOD inhibition assay --- p.31<br>Chapter 2.1.1 --- Assay development --- p.31<br>Chapter 2.1.2 --- Dose-dependent study --- p.32<br>Chapter 2.1.3 --- Reversibility of the enzyme inhibition --- p.32<br>Chapter 2.1.4 --- Lineweaver-Burk plots --- p.33<br>Chapter 2.2 --- Lipid peroxidation inhibition assay of mouse liver microsomes --- p.34<br>Chapter 2.2.1 --- Preparation of mouse liver microsomes --- p.34<br>Chapter 2.2.2 --- Basis of assay --- p.34<br>Chapter 2.2.3 --- Assay procedures --- p.35<br>Chapter 2.3 --- AAPH-induced hemolysis inhibition assay --- p.36<br>Chapter 2.3.1 --- Preparation of RBC --- p.36<br>Chapter 2.3.2 --- Basis of assay --- p.36<br>Chapter 2.3.3 --- Assay procedures --- p.37<br>Chapter 2.4 --- Lipid peroxidation inhibition assay of RBC membrane --- p.38<br>Chapter 2.4.1 --- Preparation of RBC membrane --- p.38<br>Chapter 2.4.2 --- Basis of assay --- p.39<br>Chapter 2.4.3 --- Assay procedures --- p.40<br>Chapter 2.5 --- ATPase protection assay --- p.41<br>Chapter 2.5.1 --- Preparation of RBC membrane --- p.41<br>Chapter 2.5.2 --- Preparation of malachite green (MG) reagent --- p.41<br>Chapter 2.5.3 --- Basis of assay --- p.41<br>Chapter 2.5.4 --- Assay procedures --- p.42<br>Chapter 2.5.5 --- Determination of ATPase activities --- p.43<br>Chapter 2.5.6 --- Assay buffers --- p.43<br>Chapter 2.6 --- Sulfhydryl group protection assay --- p.44<br>Chapter 2.6.1 --- Preparation of RBC membrane --- p.44<br>Chapter 2.6.2 --- Basis of assay --- p.45<br>Chapter 2.6.3 --- Assay procedures --- p.45<br>Chapter 2.7 --- Lipid peroxidation inhibition assay of LDL by the AAPH method --- p.46<br>Chapter 2.7.1 --- Basis of assay --- p.46<br>Chapter 2.7.2 --- Assay procedures --- p.46<br>Chapter 2.8 --- Lipid peroxidation inhibition assay of LDL by the hemin method --- p.47<br>Chapter 2.8.1 --- Basis of assay --- p.47<br>Chapter 2.8.2 --- Assay procedures --- p.47<br>Chapter 2.9 --- Protein assay --- p.48<br>Chapter 2.10 --- Statistical analysis --- p.48<br>Chapter 2.11 --- Test compounds --- p.48<br>Chapter Chapter 3 --- Xanthine oxidase inhibition assay: results and discussion --- p.49<br>Chapter 3.1 --- Introduction --- p.49<br>Chapter 3.2 --- Results --- p.54<br>Chapter 3.3 --- Discussion --- p.59<br>Chapter Chapter 4 --- Lipid peroxidation inhibition in mouse liver microsomes: results and discussion --- p.64<br>Chapter 4.1 --- Introduction --- p.64<br>Chapter 4.2 --- Results --- p.64<br>Chapter 4.3 --- Discussion --- p.69<br>Chapter Chapter 5 --- Assays on protection of RBC from oxidative damage: results and discussion --- p.71<br>Chapter 5.1 --- Introduction --- p.71<br>Chapter 5.2 --- Results --- p.75<br>Chapter 5.2.1 --- AAPH-induced hemolysis inhibition assay --- p.75<br>Chapter 5.2.2 --- Lipid peroxidation inhibition assay of RBC membranes --- p.82<br>Chapter 5.2.3 --- Ca2+-ATPase protection assay --- p.88<br>Chapter 5.2.4 --- Na+/K+-ATPase protection assay --- p.95<br>Chapter 5.2.5 --- Sulfhydryl group protection assay --- p.100<br>Chapter 5.3 --- Discussion --- p.110<br>Chapter 5.3.1 --- AAPH-induced hemolysis inhibition assay --- p.110<br>Chapter 5.3.2 --- Lipid peroxidation inhibition assay of RBC membranes --- p.111<br>Chapter 5.3.3 --- Ca2+-ATPase protection assay --- p.113<br>Chapter 5.3.4 --- Na+/K+-ATPase protection assay --- p.114<br>Chapter 5.3.5 --- Sulfhydryl group protection assay --- p.115<br>Chapter 5.3.6 --- Chapter summary --- p.117<br>Chapter Chapter 6 --- Lipid peroxidation inhibition assay of LDL: results and discussion --- p.118<br>Chapter 6.1 --- Introduction --- p.118<br>Chapter 6.2 --- Results --- p.118<br>Chapter 6.3 --- Discussion --- p.134<br>Chapter Chapter 7 --- General discussion --- p.137<br>References --- p.142