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Duchenne muscular dystrophy is a debilitating genetic disorder characterized by severe muscle wasting and early death in affected boys. The primary cause of this disease is mutations in the dystrophin gene resulting in the loss of the dystrophin protein from the plasma membrane of muscle fibers. In the absence of dystrophin, muscles undergo massive muscle degeneration and inflammation. Inflammation is believed to contribute substantially to dystrophic muscle pathology. The transcription factor NF-κB regulates inflammatory gene expression and provides a logical target for therapeutic treatments. Green tea extract and its primary polyphenol, epigallocatechin gallate, have been shown to have anti-inflammatory properties and to improve dystrophic muscle pathology. The purpose of these studies was to determine if dietary treatment with green tea extract or epigallocatechin gallate administered prior to disease onset could reduce dystrophic muscle pathology during the early disease time course and identify potential mechanisms through which NF-κB may be involved. Green tea extract has been shown to decrease muscle pathology and increase muscle function in mdx mice, a dystrophic mouse model. These changes have been attributed to the antioxidant potential of epigallocatechin gallate; however, other mechanisms such as suppression of the inflammatory response have not been evaluated. In the studies reported herein, both green tea extract and epigallocatechin gallate significantly decreased muscle pathology in mdx mice when provided in their diets prior to disease onset. In green tea extract (0.25% and 0.5%) treated mdx mice, serum creatine kinase, a systemic marker of muscle damage, was decreased by 85% at age 42 days. Normal fiber morphology in the tibialis anterior muscle was increased by 32% at this age (P≤0.05). The primary histopathological change was a 21% decrease in regenerating fibers (P≤0.05). NF-κB staining in central nuclei of regenerating fibers was decreased by 34% (P≤0.05). In epigallocatechin gallate (0.1%) treated mdx mice, serum creatine kinase was unchanged; however, normal fiber morphology in the tibialis anterior was increased by 20% at ages 28 and 42 days (P≤0.05). At age 42 days, the primary histopathological change was a 21% decrease in regenerating fibers (P≤0.05). NF-κB staining in central nuclei of regenerating muscle fibers was decreased by 21% at this age (P≤0.05). Epigallocatechin gallate appears to be the primary polyphenol of green tea extract responsible for many of the beneficial changes in dystrophic muscle. These data suggest that both green tea extract and epigallocatechin gallate decrease NF-κB activity in regenerating fibers resulting in reduced muscle pathology. Complimentary and alternative medicine approaches, including the use of green tea, provide important therapeutic options for ameliorating Duchenne muscular dystrophy. Green tea extract and epigallocatechin gallate are effective at decreasing muscle pathology potentially by reducing NF-κB activity in regenerating fibers in mdx mice. Use of these botanicals appears to elicit a beneficial response in dystrophic muscle that may ultimately lead to effective therapies for patients with this incurable disease. / Ph. D.

No / Green tea catechins (GTC) reduce UV radiation (UVR)-induced inflammation in experimental models, but human studies are scarce and their cutaneous bioavailability and mechanism of photoprotection are unknown. We aimed to examine oral GTC cutaneous uptake, ability to protect human skin against erythema induced by a UVR dose range and impact on potent cyclo-oxygenase- and lipoxygenase-produced mediators of UVR inflammation, PGE2 and 12-hydroxyeicosatetraenoic acid (12-HETE), respectively. In an open oral intervention study, sixteen healthy human subjects (phototype I/II) were given low-dose GTC (540 mg) with vitamin C (50 mg) daily for 12 weeks. Pre- and post-supplementation, the buttock skin was exposed to UVR and the resultant erythema quantified. Skin blister fluid and biopsies were taken from the unexposed and the UVR-exposed skin 24 h after a pro-inflammatory UVR challenge (three minimal erythema doses). Urine, skin tissue and fluid were analysed for catechin content and skin fluid for PGE2 and 12-HETE by liquid chromatography coupled to tandem MS. A total of fourteen completing subjects were supplement compliant (twelve female, median 42·5 years, range 29–59 years). Benzoic acid levels were increased in skin fluid post-supplementation (P= 0·03), and methylated gallic acid and several intact catechins and hydroxyphenyl-valerolactones were detected in the skin tissue and fluid. AUC analysis for UVR erythema revealed reduced response post-GTC (P= 0·037). Pre-supplementation, PGE2 and 12-HETE were UVR induced (P= 0·003, 0·0001). After GTC, UVR-induced 12-HETE reduced from mean 64 (sd 42) to 41 (sd 32) pg/μl (P= 0·01), while PGE2 was unaltered. Thus, GTC intake results in the incorporation of catechin metabolites into human skin associated with abrogated UVR-induced 12-HETE; this may contribute to protection against sunburn inflammation and potentially longer-term UVR-mediated damage.

O chá verde (CV) é um fitoterápico produzido a partir da planta Camellia sinensis e apresenta propriedades antioxidantes, anti-inflamatórias, anticancerígenas e antiobesidade. Foi realizado um estudo para investigar se o CV seria capaz de modular alguns parâmetros funcionais de linfócitos de animais induzidos à obesidade por dieta hipercalórica. Os grupos suplementados receberam 500 mg/kg de CV durante 22 dias seguida da dieta hipercalórica por mais 44 dias acompanhada também do tratamento com o CV. O tratamento com o CV reduziu a proliferação celular, a atividade das enzimas metabólicas hexoquinase e glicose-6-fosfato desidrogenase, aumentou a atividade de enzimas antioxidantes, diminuiu a produção de espécies reativas de oxigênio, a produção de citocinas pró- inflamatórias (IL-6, IL-1β, TNF-α) e restaurou os índices de IL-10 que se encontrava diminuído no grupo obeso. Os efeitos observados pelo CV podem proporcionar um ambiente mais adequado para o bom funcionamento celular, diminuindo a produção de mediadores inflamatórios que estão presente na obesidade. / Green tea (GT) is a phytochemical produced from Camellia sinensis and it has anti-inflammatory, anti-cancer, anti-obesity and antioxidant properties. This study was conducted to investigate whether the GT was able to modulate some lymphocyte functional parameters of obesity - induced animals by hypercaloric diet. Supplemented groups received 500 mg/kg GT for 22 days followed by hypercaloric diet for additional 44 days, together with the GT treatment. Treatment with GT reduced the cell proliferation capacity, the activity of metabolic enzymes hexokinase and glucose-6-phosphate dehydrogenase, increased the activity of antioxidant enzymes, decreased the production of reactive oxygen species, production of proinflammatory cytokines (IL-6, IL-1β, TNF-α) and restored the levels of IL-10 which was reduced by obesity. The GT effects can provide a more suitable environment for proper lymphocyte function, also reducing production of inflammatory mediators in obesity.

Extratos vegetais ricos em compostos antioxidantes têm sido amplamente utilizados em produtos cosméticos uma vez que esses compostos poderiam proteger a pele contra os danos da radiação ultravioleta (UV). Assim, o objetivo do presente trabalho foi desenvolver formulações cosméticas contendo extratos de chá verde (CV) e Ginkgo biloba (GB) a fim de avaliar a eficácia pré-clínica, na proteção contra danos causados pela radiação UV, a penetração cutânea e a segurança de tais formulações. Para tal, foram desenvolvidas 13 formulações e após os testes de estabilidade e sensorial, foi selecionada uma formulação a base de fosfato de trilaureth-4 e goma polissacarídica para a realização dos estudos propostos. A eficácia pré-clínica foi realizada por testes in vitro (atividade antioxidante) e in vivo em animais de laboratório, os quais foram submetidos à radiação UV para a avaliação dos efeitos fotoprotetores das formulações objeto de estudo. O estudo de penetração cutânea foi feito em células de difusão de Franz utilizando pele humana e o de segurança por meio da avaliação da compatibilidade cutânea (estudo clínico). Ambos os extratos, CV e GB, apresentaram atividade antioxidante in vitro, no entanto, CV apresentou maior efeito que GB. Na avaliação da eficácia in vivo, foi observado que somente as formulações acrescidas dos extratos vegetais protegeram a pele dos animais contra os danos induzidos pela radiação UV, quando comparadas ao controle irradiado. A formulação que continha GB apresentou efeitos mais pronunciados na proteção da função barreira da pele e contra o eritema, enquanto que a formulação acrescida de CV atuou de maneira mais pronunciada na proteção contra a formação de células de queimadura solar. Os resultados referentes ao estudo de penetração cutânea mostraram que a epigalocatequina-3- galato (EGCG), proveniente da formulação que continha CV, e, a quercetina proveniente da formulação acrescida de GB, penetraram na pele, mas não permearam até o líquido receptor, ou seja, ficaram retidas no estrato córneo e na epiderme viável, sendo que no caso de EGCG, pequenas concentrações também foram encontradas na derme. O estudo de segurança mostrou que as diferentes formulações objeto de estudo apresentaram uma ótima compatibilidade cutânea. Considerando que as formulações contendo os extratos vegetais de CV e de GB apresentaram efeitos fotoprotetores in vivo, penetração e retenção de seus flavonóides majoritários na pele e ótima compatibilidade cutânea, pode-se considerar que tais formulações apresentam eficácia e segurança para uso cosmético. Além disso, os resultados obtidos neste estudo contribuíram para mostrar a importância da associação dos extratos de chá verde e de Ginkgo biloba em formulações cosméticas com finalidades fotoprotetoras uma vez que estes extratos apresentam efeitos que se complementam na proteção da pele contra o conjunto de danos induzidos pela radiação UV. / Botanical extracts rich in antioxidant compounds have been widely used in cosmetic products since they could protect the skin against UV-induced damages. Thus, the objective of this study was to develop cosmetic formulations containing green tea (GT) and Ginkgo biloba (GB) extracts in order to evaluate the preclinical efficacy on the skin protection against UV-induced damages, skin penetration and safety of these formulations. For this, 13 formulations were developed and the formulation number 11, containing trilaureth-4 phosphate and a polysaccharide gum, was chosen for the next studies, after stability and sensorial analysis. The pre-clinical efficacy was done by in vitro (antioxidant activity) and in vivo tests in animal skin submitted to UV radiation in order to evaluate the photoprotective effects of the formulations. The skin penetration study was carried out by using human skin biopsies and Franz diffusion cells. The safety study was performed by a skin compatibility test (clinical study). Both extracts presented antioxidant activity, however GT showed higher antioxidant effect than GB. The in vivo efficacy evaluation showed that only the extracts supplemented formulations protected the skin against UV damages, when compared to the irradiated control. The formulation containing GB was more effective in protecting against skin barrier damages and erythema formation, while the formulation containing GT had more pronounced effects against sunburn cell formation. The results of the skin penetration study showed that epigalocatechin-3- galate (EGCG) from GT containing formulation, and quercetin from GB containing formulation penetrated the skin but they were not able to permeate further through the skin to the receptor fluid, that is, these flavonoids were retained into the stratum corneum and viable epidermis. In addition, small quantities of EGCG were found in dermis. The safety study showed that the formulations under study presented very good skin compatibility. Considering that the formulations containing GT and GB provided in vivo photoprotective effects, penetration and retention of their mainly flavonoids into the skin and good skin compatibility as well, we can consider that these formulations present efficacy and safety for cosmetic use. In addition, the results contributed to demonstrate the importance of the combination of these two extracts in cosmetic formulations with photoprotective purpose since both extracts had complementary effects on the constellation of UV-induced skin damages.

O chá é uma das bebidas mais consumidas no mundo. Os chás provenientes da planta Camellia sinensis possuem altos teores de antioxidantes, o que significa que podem ter diversos efeitos benéficos na preservação da saúde. Durante séculos, a humanidade procura formas de conservar melhor e por mais tempo os alimentos que consomem. O processo de irradiação de alimentos é uma técnica amplamente utilizada em todo o mundo e é indicada por diversos órgãos de saúde e sanitários de diversos países. A radiação interage com o material causando dois tipos de efeitos, o efeito direto e o efeito indireto. No efeito direto a radiação interage com a molécula de DNA, causando a quebra dessa molécula, inativando a célula. No efeito indireto, que representa 70% da interação, a radiação quebra a molécula de água presente no meio, em um processo chamado de radiólise, criando uma série de radicais livres que vão interagir com os componentes celulares, levando a morte da célula. Portanto, o objetivo deste trabalho foi estudar os efeitos da radiação gama em dois tipos de chás da planta Camellia sinensis irradiados com diferentes valores de atividade de água. As amostras de chá verde e chá preto tiveram suas Aw ajustadas a três valores (Aw alta, Aw média e Aw baixa). As amostras foram irradiadas em fonte de 60Co nas doses de 0; 1,0; 1,5; 2,0; 2,5; 5,0; 7,5 e 10,0 kGy. As análises utilizadas foram: microbiologia por semeadura de superfície, quantificação de fenólicos totais, análise da atividade antioxidante por ORAC e identificação e quantificação dos principais antioxidantes presente nessas bebidas. Foi possível constatar que quanto maior a quantidade de água livre presente no meio, menor foi a dose para realizar o controle microbiológico. O chá verde mostrou ser um pouco mais suscetível a irradiação com alta Aw do que o chá preto, pois houve variação da quantidade de fenólicos e flavonóides, diminuindo a quantidade desses compostos em algumas doses, mas também houve aumento da quantidade em outras doses. Entretanto em ambos os chás, essas mudanças podem ser consideradas insignificantes, uma vez que não houve diferença da atividade antioxidante em doses de até 10 kGy. A dose de 5,0 kGy foi a dose mínima que garantiu o controle microbiológico e não causou alterações nos parâmetros analisados. / Tea is the most consumed beverage in the world. Teas from Camellia sinensis plant have high levels of antioxidants, which mean that they may have several beneficial effects on health preservation. For centuries, mankind looks for ways to conserve better and for a longer time the food that they eat. The food irradiation process is a largely technique used worldwide, and is recommended by many health agencies and authorities of several countries. The radiation interacts with the material causing two kinds of effects, the direct and the indirect effect. In the direct effect the radiation interacts with the DNA molecule, breaking it, and then inactivates the cell. In the indirect effect, which represents 70% of the interaction, the radiation breaks the water molecule in a process denominated radiolysis, creating a number of free radicals that will interact with the cellular components, leading to the cell death. Therefore, the aim of this work is to study the effects of gamma radiation on two kinds of tea from Camellia sinensis plant irradiated with different water activities. The green tea and black tea samples had their Aw adjusted to three values (high Aw, medium Aw, and low Aw). The samples were irradiated in 60Co source at doses of 0, 1.0, 1.5, 2.0, 2.5, 5.0, 7.5, and 10.0 kGy. The analyses used were: microbiology by plate count, total phenolic compounds quantification, antioxidant activity by ORAC assay, and identification and quantification of main antioxidants in these beverages. It was noted that the greater the quantity of free water present in the medium, the lower was the dose to achieve microbiological control. The green tea showed to be a little more susceptible to irradiation by high Aw once there was more variation in the amount of flavonoids and phenolics than the black tea, decreasing the amount of these compounds in some doses, but increasing the amount in other ones. However in both teas, these changes can be considered insignificant, since there was no difference in antioxidant activity at doses up to 10 kGy. The dose of 5.0 kGy was the minimum dose that secured the microbiological control and had no changes on the parameters analyzed.

Orientador: Paula Schimidt Azevedo Gaiolla / Resumo: INTRODUÇÃO: A doxorrubicina (DOX) é um medicamento muito eficaz no tratamento de vários tipos de câncer, mas seu uso em larga escala tem causado preocupação devido à cardiotoxicidade causada pela droga. Não se sabe exatamente quais mecanismos estão envolvidos, mas acredita-se nos papeis centrais da ligação da DOX com a topoisomerase 2-β (Top2-β), que é uma enzima que protege a célula da citotoxicidade e destruição; da interação DOX-ferro gerando espécies reativas de oxigênio; além de disfunção mitocondrial, seguida por muitas outras vias secundárias ativadas por essas primárias, como inflamação e fatores da matriz extracelular (MEC). Por outro lado, o chá verde, uma bebida muito popular em todo o mundo, tem efeitos antioxidantes e antitumorais. MÉTODOS: Foram utilizados 60 ratos Wistar machos. Estes animais foram divididos grupos: C=20 (controle) que recebeu ração padrão e administração intraperitoneal de salina, CV=20 (controle + chá verde) que receberam ração adicionada de extrato de chá verde e administração intraperitoneal de solução salina, D=20 (doxorrubicina) que recebeu ração padrão e administração intraperitoneal de doxorrubicina e DCV=20 (doxorrubicina + chá verde) que receberam ração adicionada de extrato de chá verde e administração intraperitoneal de doxorrubicina. A ração foi oferecida por 35 dias e no 33º dia a infusão de doxorrubicina ou soro fisiológico foi realizada na mesma proporção (20 mg / kg em dose única) e os animais foram eutanasiados 48 horas após a... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: INTRODUCTION: doxorubicin (dox) is a very effective drug in the treatment of several types of cancer, but it plays an important role in cardiotoxicity. The mechanisms of DOX-induced cardiotoxicity include: binding to Top2-β, an enzyme that protects cells from citotoxicity and destruction; interaction with iron and altering intracellular and mitochondrial antioxidants enzymes activities, followed by many other secondary pathways activated by these primary, for example inflammation, estracellular matrix ( ECM) factors and others. On the other hand, green tea, a very popular beverage all over the world, has antioxidants and antitumor properties. METHODS: Sixty male Wistar rats were used. These animals were divided into groups: C = 20 (control) that received standard chow and intraperitoneal administration of saline, GT = 20 (control + green tea) receiving added chow of green tea extract and intraperitoneal administration of saline solution, D = 20 (doxorubicin) who received standard chow and intraperitoneal administration of doxorubicin and DGT = 20 (doxorubicin + green tea) who received added ration of green tea extract and intraperitoneal administration of doxorubicin. The feed was offered for 35 days and on the 33rd day the infusion of doxorubicin or saline was performed in the same proportion (20 mg / kg in a single dose) and the animals were euthanized 48 hours after the injection of the drug. The rats were submitted to echocardiogram to evaluate the cardiac morphology and ... (Complete abstract click electronic access below) / Doutor

Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 218-235). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Li, Yuk Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 121-132). / Abstracts in English and Chinese. / ACKNOWLEDGMENTS --- p.i / ABSTRACT --- p.ii / LIST OF ABBREVATIONS --- p.vii / TABLE OF CONTENTS --- p.x / Chapter Chapter 1 --- General Introduction / Chapter 1.1 --- Introduction --- p.1 / Chapter 1.2 --- Theories of aging --- p.2 / Chapter 1.2.1 --- Free radical theory of aging --- p.3 / Chapter 1.2.2 --- Free radicals reactions and their effects --- p.4 / Chapter 1.2.2.1 --- Lipid peroxidation --- p.6 / Chapter 1.2.2.2 --- Protein oxidation --- p.6 / Chapter 1.2.2.3 --- DNA oxidation --- p.8 / Chapter 1.2.2.4 --- Carbohydrate oxidation --- p.8 / Chapter 1.2.3 --- Antioxidant defense systems --- p.9 / Chapter 1.2.3.1 --- Superoxide dismutase (SOD) --- p.9 / Chapter 1.2.3.2 --- Catalase --- p.11 / Chapter 1.2.3.3 --- Glutathione peroxidase (GPx) and reductase --- p.11 / Chapter 1.3 --- Models on aging study --- p.12 / Chapter 1.3.1 --- Non-mammalian model systems --- p.12 / Chapter 1.3.1.1 --- History of Drosophila on longevity study --- p.14 / Chapter 1.3.1.2 --- Advantages of Drosophila model --- p.14 / Chapter 1.3.2 --- Mammalian model systems --- p.15 / Chapter 1.4 --- Antioxidant effects on aging process --- p.16 / Chapter 1.4.1 --- Antioxidant capacity of tea --- p.16 / Chapter 1.4.2 --- Antioxidant capacity of vegetables --- p.19 / Chapter 1.5 --- Dietary fat on longevity --- p.21 / Chapter Chapter 2 --- Anti-aging: Effects of Green Tea Catechins on Life Span and Antioxidant Enzymes of Drosophila melanogaster / Chapter 2.1 --- Introduction --- p.24 / Chapter 2.2 --- Gbjectives --- p.27 / Chapter 2.3 --- Materials and methods --- p.28 / Chapter 2.3.1 --- Materials --- p.28 / Chapter 2.3.2 --- Preparation of GTCs --- p.28 / Chapter 2.3.3 --- Feeding experiment --- p.30 / Chapter 2.3.3.1 --- Dose determination --- p.31 / Chapter 2.3.3.2 --- Paraquat treatment --- p.31 / Chapter 2.3.3.3 --- Hydrogen peroxide (H202) treatment --- p.33 / Chapter 2.3.3.4 --- Enzyme activity assay --- p.34 / Chapter 2.3.4 --- Enzyme analysis --- p.34 / Chapter 2.3.4.1 --- SOD activity --- p.34 / Chapter 2.3.4.2 --- Catalase activity --- p.35 / Chapter 2.3.4.3 --- Lipid hydorperoxies (LOOHs) formation --- p.36 / Chapter 2.3.4.4 --- Determination of protein concentration --- p.37 / Chapter 2.3.5 --- Semi-quantitative RT-PCR assay --- p.37 / Chapter 2.3.5.1 --- RNA isolation --- p.37 / Chapter 2.3.5.2 --- Primer sequences --- p.38 / Chapter 2.3.5.3 --- Reverse Transcriptase PCR --- p.40 / Chapter 2.3.6 --- Statistics --- p.40 / Chapter 2.4 --- Results --- p.42 / Chapter 2.4.1 --- Dose determination --- p.42 / Chapter 2.4.2 --- Paraquat treatment --- p.45 / Chapter 2.4.3 --- H202 treatment --- p.48 / Chapter 2.4.4 --- SOD activity --- p.51 / Chapter 2.4.5 --- Catalase activity --- p.51 / Chapter 2.4.6 --- LOOHs formation --- p.53 / Chapter 2.4.7 --- Semi-quantitative RT-PCR assay --- p.53 / Chapter 2.5 --- Discussion --- p.55 / Chapter Chapter 3 --- Anti-aging: Effects of Vegetable Extracts on Life Span and Antioxidant Enzymes of Drosophila melanogaster / Chapter 3.1 --- Introduction --- p.62 / Chapter 3.2 --- Objectives --- p.64 / Chapter 3.3 --- Materials and methods --- p.65 / Chapter 3.3.1 --- Materials --- p.65 / Chapter 3.3.2 --- Preparation of vegetables extracts --- p.65 / Chapter 3.3.3 --- Feeding experiment --- p.65 / Chapter 3.3.3.1 --- Dose determination --- p.66 / Chapter 3.3.3.2 --- Paraquat and hydrogen peroxide (H2O2) treatment --- p.67 / Chapter 3.3.4 --- Lipid hydroperoxide (LOOHs) formation --- p.67 / Chapter 3.3.5 --- Enzyme analysis --- p.67 / Chapter 3.3.6 --- Semi-quantitative RT-PCR assay --- p.67 / Chapter 3.3.7 --- Statistics --- p.68 / Chapter 3.4 --- Results --- p.69 / Chapter 3.4.1 --- Dose determination --- p.69 / Chapter 3.4.2 --- Antioxidant effect among different vegetables --- p.69 / Chapter 3.4.3 --- SOD activity --- p.76 / Chapter 3.4.4 --- Catalase activity --- p.76 / Chapter 3.4.5 --- LOOHs formation --- p.78 / Chapter 3.4.6 --- Semi-quantitative RT-PCR assay --- p.78 / Chapter 3.5 --- Discussion --- p.80 / Chapter Chapter 4 --- Anti-aging Activity of Greeen Tea Catechins and Broccoli Extracts in Drosophila melanogaster Fed a High Fat Diet / Chapter 4.1 --- Introduction --- p.85 / Chapter 4.2 --- Objectives --- p.87 / Chapter 4.3 --- Materials and methods --- p.88 / Chapter 4.3.1 --- Materials --- p.88 / Chapter 4.3.2 --- Preparation of free fatty acid --- p.88 / Chapter 4.3.3 --- Prepartion of GTCs and BEs --- p.89 / Chapter 4.3.4 --- Feeding experiment --- p.89 / Chapter 4.3.5 --- LOOHs formation --- p.90 / Chapter 4.3.6 --- Enzyme analysis --- p.91 / Chapter 4.3.7 --- Semi-quantitative RT-PCR assay --- p.91 / Chapter 4.3.8 --- Statistics --- p.91 / Chapter 4.4 --- Results --- p.92 / Chapter 4.4.1 --- Dose determination --- p.92 / Chapter 4.4.2 --- Effects of GTCs or BEs on life span with lard consumption --- p.95 / Chapter 4.4.3 --- LOOHs formation --- p.101 / Chapter 4.4.4 --- SOD activity --- p.103 / Chapter 4.4.5 --- Catalase activity --- p.107 / Chapter 4.4.6 --- Semi-quantitative RT-PCR assay --- p.110 / Chapter 4.5 --- Discussion --- p.112 / References --- p.121