Ma, Ka Ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 113-129). / Abstracts in English and Chinese. / ACKNOWLEDGMENTS --- p.I / ABSTRACT --- p.II / LIST OF ABBREVIATIONS --- p.VII / TABLE OF CONTENTS --- p.IX / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Calcium --- p.1 / Chapter 1.1.1 --- Recommendation of calcium intake --- p.1 / Chapter 1.1.2 --- Calcium toxicity --- p.2 / Chapter 1.1.3 --- Calcium homeostasis --- p.2 / Chapter 1.1.3.1 --- Role of parathyroid hormone in calcium homeostasis --- p.4 / Chapter 1.1.3.2 --- "Role of 1,25-dihydroxyvitamin D3 in calcium homeostasis" --- p.4 / Chapter 1.1.3.3 --- Role of calcitonin in calcium homeostasis --- p.6 / Chapter 1.2 --- Magnesium --- p.7 / Chapter 1.2.1 --- Recommendation of magnesium intake --- p.7 / Chapter 1.2.2 --- Absorption and secretion of magnesium --- p.8 / Chapter 1.3 --- Cholesterol --- p.9 / Chapter 1.3.1 --- Cholesterol homeostasis --- p.11 / Chapter 1.3.1.1 --- Role of LDLR --- p.14 / Chapter 1.3.1.2 --- Role of SREBP-2 --- p.17 / Chapter 1.3.1.3 --- HMGR as rate limiting step for cholesterol synthesis --- p.19 / Chapter 1.3.1.4 --- CYP7A1 as a key factor in production of bile acids --- p.21 / Chapter 1.3.1.5 --- Role of LXR in production of bile acids --- p.22 / Chapter 1.3.1.6 --- AC AT regulates cholesterol uptake in intestine --- p.22 / Chapter Chapter 2 --- Effect of Calcium Deficiency and Inadequacy on Blood Cholesterol Level in Intact Male and Castrated Hamsters --- p.25 / Chapter 2.1 --- Introduction --- p.25 / Chapter 2.2 --- Objective --- p.28 / Chapter 2.3 --- Materials and methods --- p.29 / Chapter 2.3.1 --- Hamsters --- p.29 / Chapter 2.3.1.1 --- Intact male hamster --- p.29 / Chapter 2.3.1.2 --- Castrated hamster --- p.30 / Chapter 2.3.2 --- Diets --- p.31 / Chapter 2.3.3 --- Determination of calcium content in animal diet --- p.33 / Chapter 2.3.4 --- "Determination of serum lipid, lipoproteins and calcium concentration" --- p.33 / Chapter 2.3.5 --- Determination of cholesterol concentration in organs --- p.34 / Chapter 2.3.6 --- Determination of fecal neutral and acidic sterols --- p.37 / Chapter 2.3.7 --- Determination of fecal neutral sterols --- p.37 / Chapter 2.3.8 --- Determination of fecal acidic sterols --- p.40 / Chapter 2.3.9 --- Statistics --- p.42 / Chapter 2.4 --- Results on intact male hamsters --- p.43 / Chapter 2.4.1 --- Diet composition --- p.43 / Chapter 2.4.2 --- Growth and food intake --- p.43 / Chapter 2.4.3 --- Organ weights --- p.43 / Chapter 2.4.4 --- Effect of calcium deficiency diet on the plasma lipid profile and calcium concentration of hamsters --- p.43 / Chapter 2.4.5 --- Effect of calcium deficiency diet on hepatic cholesterol of hamsters --- p.44 / Chapter 2.4.6 --- Effect of calcium on fecal neutral sterol output --- p.48 / Chapter 2.4.7 --- Effect of calcium on fecal acidic sterol output --- p.48 / Chapter 2.5 --- Results on castrated hamsters --- p.50 / Chapter 2.5.1 --- Growth and food intake --- p.50 / Chapter 2.5.2 --- Organ weights --- p.50 / Chapter 2.5.3 --- Effect of calcium deficiency diet on the plasma lipid profile and calcium concentration of hamsters --- p.50 / Chapter 2.5.4 --- Hepatic cholesterol --- p.50 / Chapter 2.5.5 --- Effect of calcium on fecal neutral sterol output --- p.53 / Chapter 2.5.6 --- Effect of calcium on fecal acidic sterol output --- p.53 / Chapter 2.6 --- Discussion --- p.55 / Chapter Chapter 3 --- Effect of Calcium Deficiency and Inadequacy on Blood Cholesterol Level in Intact Female and Ovariectomized Hamsters --- p.57 / Chapter 3.1 --- Introduction --- p.57 / Chapter 3.2 --- Objective --- p.58 / Chapter 3.3 --- Materials and methods --- p.59 / Chapter 3.3.1 --- Hamsters --- p.59 / Chapter 3.3.1.1 --- Intact female hamster --- p.59 / Chapter 3.3.1.2 --- Ovariectomized hamster --- p.60 / Chapter 3.3.2 --- Diets --- p.60 / Chapter 3.3.3 --- "Determination of serum lipid, lipoproteins and calcium concentration" --- p.60 / Chapter 3.3.4 --- "Determination of cholesterol concentration in organs, fecal neutral and acidic sterols" --- p.60 / Chapter 3.3.5 --- "Western blottting of liver SREBP-2, LDLR, HMGR, LXR and CYP7A1 proteins" --- p.61 / Chapter 3.3.6 --- Preparation of intestinal microsome --- p.62 / Chapter 3.3.7 --- Intestinal acyl coenzyme A: cholesterol acyltransferase (ACAT) activity measurement --- p.63 / Chapter 3.3.8 --- Statistics --- p.64 / Chapter 3.4 --- Results on intact female hamsters --- p.65 / Chapter 3.4.1 --- Growth and food intake --- p.65 / Chapter 3.4.2 --- Organ weights --- p.65 / Chapter 3.4.3 --- Effect of calcium deficiency diet on the plasma lipid profile and calcium concentration of hamsters --- p.65 / Chapter 3.4.4 --- Effect of calcium deficiency diet on hepatic cholesterol of hamsters --- p.65 / Chapter 3.4.5 --- Effect of dietary calcium on fecal neutral sterol output --- p.66 / Chapter 3.4.6 --- Effect of dietary calcium on fecal acidic sterol output --- p.66 / Chapter 3.4.7 --- Effect of dietary calcium on liver LDLR immunoreactive mass --- p.71 / Chapter 3.4.8 --- Effect of dietary calcium on liver CYP7A1 immunoreactive mass --- p.71 / Chapter 3.4.9 --- Effect of dietary calcium on liver LXR immunoreactive mass --- p.71 / Chapter 3.4.10 --- Effect of dietary calcium on liver SREBP-2 immunoreactive mass --- p.71 / Chapter 3.4.11 --- Effect of dietary calcium on liver HMGR immunoreactive mass --- p.71 / Chapter 3.4.12 --- Effect of dietary calcium deficiency on intestinal ACAT activity --- p.77 / Chapter 3.5 --- Results on ovariectomized hamsters --- p.79 / Chapter 3.5.1 --- Growth and food intake --- p.79 / Chapter 3.5.2 --- Organ weights --- p.79 / Chapter 3.5.3 --- Effect of calcium deficiency diet on plasma lipid profile and calcium concentration of hamsters --- p.79 / Chapter 3.5.4 --- Hepatic cholesterol --- p.79 / Chapter 3.5.5 --- Effect of dietary calcium on fecal neutral sterol output --- p.80 / Chapter 3.5.6 --- Effect of dietary calcium on fecal acidic sterol output --- p.80 / Chapter 3.5.7 --- Effect of dietary calcium on liver LDLR immunoreactive mass --- p.85 / Chapter 3.5.8 --- Effect of dietary calcium on liver CYP7A1 immunoreactive mass --- p.85 / Chapter 3.5.9 --- Effect of dietary calcium on liver LXR immunoreactive mass --- p.85 / Chapter 3.5.10 --- Effect of dietary calcium on liver SREBP-2 immunoreactive mass --- p.85 / Chapter 3.5.11 --- Effect of dietary calcium on liver HMGR immunoreactive mass … --- p.85 / Chapter 3.6 --- Discussion --- p.91 / Chapter Chapter 4 --- Effect of Dietary Magnesium Supplementation on Blood Cholesterol Level in Intact Male Hamsters --- p.94 / Chapter 4.1 --- Introduction --- p.94 / Chapter 4.2 --- Objective --- p.96 / Chapter 4.3 --- Materials and methods --- p.97 / Chapter 4.3.1 --- Hamsters --- p.97 / Chapter 4.3.2 --- Diets --- p.98 / Chapter 4.3.3 --- "Determination of serum lipid, lipoproteins and magnesium concentration" --- p.100 / Chapter 4.3.4 --- "Determination of cholesterol concentration in organ, fecal neutral and acidic sterols" --- p.100 / Chapter 4.3.5 --- Statistics --- p.100 / Chapter 4.4 --- Results on male hamster --- p.101 / Chapter 4.4.1 --- Growth and food intake --- p.101 / Chapter 4.4.2 --- Organ weights --- p.101 / Chapter 4.4.3 --- Effect of dietary magnesium on plasma lipid profile and magnesium concentration in hamsters --- p.101 / Chapter 4.4.4 --- Effect of dietary magnesium on hepatic cholesterol of hamsters..… --- p.102 / Chapter 4.4.5 --- Effect of dietary magnesium on fecal neutral sterol output --- p.105 / Chapter 4.4.6 --- Effect of dietary magnesium on fecal acidic sterol output --- p.105 / Chapter 4.6 --- Discussion --- p.107 / Chapter Chapter 5 --- Conclusion --- p.110 / References --- p.113

Fertilization is a process that generates the first cell of a new organism. In mammals, fertilization occurs in the female reproductive tract. The male gametes (spermatozoa) are rendered fertilization-competent only after they undergo capacitation and acrosome reaction (AR). The set of physiological changes, characterised by the acquisition of hyperactivated motility, that render the spermatozoa fertilization competent is known as capacitation. Using in vitro models, the complex intracellular signaling events mediating this process are still being understood. This thesis explores the role of protein tyrosine phosphorylation during capacitation using the golden hamster (Mesocricetus auratus) spermatozoa. The knowledge about the molecular components involved in capacitation, apart from enriching our understanding about a basic cellular process could also provide leads in the management of male (in)fertility. A comprehensive review on the perspectives of male reproduction, spermatogenesis, the structural features of a spermatozoon and sperm maturation, relevant to the content of the thesis is provided in Chapter-1 (General Introduction). Molecular mediators that initiate capacitation include cAMP, Ca2+and HCO3- ions. These signalling molecules regulate activities of protein kinases and phosphatases, which control the level of protein phosphorylation in spermatozoa. Capacitation-associated increase in protein phosphorylation, specifically protein tyrosine phosphorylation (PYP) has been demonstrated in a few species such as mouse, rat and human. The unique nature of PYP signaling during sperm capacitation has been exemplified by discoveries of several male germ cell-specific signalling molecules like soluble adenylate cyclase. However,molecular identities of tyrosine-phosphorylated proteins and their functional role during sperm capacitation are yet to be investigated in detail. In this context, the effect of modulating intracellular levels of signaling molecules upstream of protein phosphorylation was sought using pentoxifylline (PF), a cAMP phosphodiesterase inhibitor. Interestingly, PF-induced capacitation was associated with an early induction of tyrosine phosphorylation of proteins (45-80 kDa) localized to the mid piece of the sperm tail. Interestingly, the ultrastructural localization of tyrosine-phosphorylated proteins in the sperm tail by immunoelectron microscopy (IEM) revealed most intense immunolabelling in the fibrous sheath, followed by outer dense fibers (ODFs)and the axoneme. Data pertaining to the effect of PF on sperm capacitation and the associated protein-phosphorylation is presented in Chapter-2. Since PYP was determined to be extremely critical for hyperactivation in spermatozoa, the involvement of protein tyrosine kinases (PTKs) in this process was assessed using a specific PTK inhibitor, tyrphostin A47 (TP-47: EGFR-TK specific). The third chapter deals with the effect of tyrphostins on sperm capacitation and PYP. A dose-dependent inhibition by TP-47 of capacitation and principal piece associated-PYP of ~45-60 kDa proteins was observed. Interestingly, TP-47 treated-spermatozoa exhibited a circular motility pattern; when assessed for kinematic parameters, by computer aided sperm analysis, sperm showed lower values for key kinematic parameters as compared to the controls. While sperm viability in TP-47- treated samples was not affected, the ATP content reduced towards latter (4-5 h) part of culture as compared to the controls. When spermatozoa were treated with two other PTK inhibitors, tyrphostin AG1478 (EGFR-TK specific) and tyrphostin AG1296 (PDGFR-TK specific), they did not show any changes in kinematic parameters or PYP, indicating that the TP-47-effect was compound-specific. The fourth chapter of this thesis involves the molecular analysis of proteins hypo-tyrosine phosphorylated in the presence of TP-47, which started with the enrichment of sperm flagellar proteins that are tyrosine phosphorylated during capacitation, using various detergents. Detergent extractions established that most tyrosine-phosphorylated proteins were non-membranous in nature, which complemented the IEM data. Therefore, phosphoproteome analysis of the untreated and TP-47-treated sperm samples was performed. For this, protein extracts were subjected to 2D-PAGE-phosphotyrosine immunoblots. A 51 kDa spot and two 45 kDa spots, corresponding to the hypo-tyrosine phosphorylated spots, were analyzed by MS/MS. While peptides from the 51 kDa protein matched with tektin-2 (a microtubular protein), those of the 45 kDa spots matched with ODF-2 protein of the sperm flagellum. Validation of the presence of tektin-2 and ODF-2 protein and their tyrosine-phosphorylated forms on sperm capacitation in the hamster spermatozoa has also been performed. In addition to detailing the role of PYP in hamster sperm capacitation, this study revealed the identities of a few of these proteins, whose tyrosine phosphorylated status could be critical for optimal sperm flagellar bending, required for sperm hyperactivation. By understanding causes that lead to altered sperm function, for example, as observed with hamster spermatozoa, new insights could be achieved into molecular regulatory mechanisms that govern sperm function in clinical cases of non-obstructive male infertility in the human.

Bile acid metabolism is integrally involved in cholesterol homeostasis in mammals because it is the major means by which cholesterol is eliminated from the body. We have undertaken an effort to study the molecular mechanisms underlying the regulation of bile acid metabolism by isolating and characterizing the cDNA and gene for an enzyme that hydroxylates lithocholic acid (LCA) at position 6β, lithocholic acid 6β-hydroxylase; the first bile acid-induced gene reported. LCA is a very hydrophobic, toxic bile acid formed from chenodeoxycholic acid in the gut lumen upon reduction of the 7α-hydroxy group by microbial enzymes. The proper elimination of LCA is essential for maintenance of the bile acid pool and for prevention of cholestasis which results from LCA precipitating in the cannaculi of the liver when its concentration is high. The LCA 6β-hydroxylase cDNA was isolated by differential hybridization of hamster liver libraries prepared from animals fed either a cholic acid enriched diet or a cholestipol-rich chow and was named CYP3A10 based on its homology with other cytochrome P450s (P450) in family 3A. We found that CYP3A10 was essentially expressed only in males. A statistical analysis of RNA from young males fed with cholic acid and normal chow showed that the cholic acid induction was about 50% at the RNA level. We determined the biological nature of the protein encoded by CYP3A10 by expression of the cDNA in COS cells. Microsomes prepared from transfected cells were assayed with LCA as a substrate and found to hydroxylate LCA predominantly at position 6β. We examined whether CYP3A10 could hydroxylate other steroid compounds by assays with testosterone, progesterone and androstenedione and found that, although 6β-hydroxylase (as well as others) activity was observed with all three, LCA was the preferred substrate based on kinetic analysis. A developmental time course of CYP3A10 expression in males showed little expression before puberty, a striking induction of expression at puberty and a fourfold induction thereafter through adulthood. We then examined the male-specific expression of CYP3A10 in hamster liver. We disrupted the pattern of GH secretion in male hamsters by hypophysectomy, neonatal glutamate treatment and by continuous infusion of GH via osmotic minipumps (to mimic the female pattern of GH secretion) and found no significant effect on CYP3A10 expression. Conversely, in females, hypophysectomy and neonatal glutamate treatment significantly induced CYP3A10 expression 5- to 10-fold. Additionally, when females treated neonatally with glutamate were injected twice daily with GH as adults (to mimic the male pattern of GH secretion), the levels of CYP3A10 expression were not significantly different from those of normal males. These results led us to conclude that the pattern of GH secretion in males does not control the male-specific expression of CYP3A10 but that in females expression can be induced by altering the tonic secretion of GH. No significant effect on CYP3A10 expression was observed by castration of adult males, indicating that circulating androgens were not required for expression. We found that gonadal hormones (e.g. estrogen and progesterone) do not have a suppressive effect on CYP3A10 expression in females since ovariectomy did not induce expression. Many genes are "imprinted" neonatally by exposure to a given effector for developmental-, tissue- or sexually regulated expression. We investigated whether neonatal androgen exposure was required for male-specific expression of CYP3A10 by castrating hamsters neonatally and determining the level of CYP3A10 expression in adulthood. Our results indicate that androgens are required neonatally for CYP3A10 expression since no expression was observed in neonatally castrated hamsters. We were unable to induce expression in neonatally castrated hamsters by either GH or testosterone injections. These results suggest several notable points 1) that CYP3A10 expression is programmed neonatally by androgen exposure; 2) that androgens exert their effect directly on the liver and not via the hypothalamus; 3) that neither testosterone nor GH can restore CYP3A10 expression when males have not been exposed to androgens neonatally; and 4) that in experimental conditions, females can be induced to express CYP3A10, which indicates that there are two modes for regulating expression: by "imprinting" in males and by GH and testosterone in females. We are now studying the molecular mechanisms involved in the bile acid-mediated induction and the male-specific expression of CYP3A10. We have cloned approximately 8 kb of 5' flanking DNA from a hamster genomic library and sequenced about 1 kb of proximal DNA. Primer extension and S1 digestion analyses indicate that the mRNA for CYP3A10 has multiple transcription initiation sites clustered about 90 bp from the initiator methionine codon. We have also prepared CYP3A10 promoter/lacZ chimeric constructs to begin delineating the cis-acting elements controlling CYP3A10 expression and regulation. We used H2.35 cells as recipients because they are a mouse hepatocyte cell line that has been transformed with a temperature sensitive SV40. These cells can be grown at the permissive temperature and can be induced to behave like liver cells, the differentiated condition, by switching to a nonpermissive temperature. We have found that the construct with 1 kb of proximal CYP3A10 5' flanking DNA was able to express the reporter gene at higher levels under differentiated conditions, which were consistent with higher expression of an albumin promoter/lacZconstruct, upon switching the cells to the more liver phenotype. The system characterized and described here is ideally suited for dissecting the molecular details governing bile acid-mediated regulation and sexually dimorphic expression of liver genes. Very little is known about both these very important biological phenomena. Much could be learned about transcriptional regulation of liver genes by investigating the cis-elements and trans-acting factors mediating regulation of CYP3A10 expression.

Resumo: A cavidade oral é alvo freqüente dos efeitos tóxicos dos agentes antineoplásicos por apresentar tecidos com rápida divisão celular, comparável à dos tumores malignos. Uma das complicações orais mais freqüentes da quimioterapia é a mucosite, uma alteração de caráter inflamatório para a qual ainda não existe tratamento definido. Essa complicação oral provoca desconforto e dor severa, dificulta a alimentação e pode determinar a interrupção do tratamento antineoplásico. Considerando-se a relevância clínica da mucosite, é importante encontrar meios para tratá-la. O presente estudo teve como objetivo avaliar o efeito do laser terapêutico na redução da incidência e da severidade da mucosite induzida em hamsters. O quimioterápico 5-FU foi aplicado em 60 animais nos dias 0 e 2 do experimento, nas doses de 90 e 60 mL/Kg de peso, respectivamente. Para simular o efeito de uma irritação crônica, as mucosas jugais dos animais foram escarificadas nos dias 3 e 4. Aplicou-se o laser terapêutico (InGaAlP, 683 nm, 12 J/cm2) em 5 pontos da mucosa jugal direita e esquerda de 30 animais (Grupo I), durante 7 dias. Os animais do Grupo II não receberam tratamento. O Grupo III (controle negativo) foi composto por 5 animais que não receberam o protocolo de indução de mucosite. Nos dias 0, 4, 8, 12 e 15 do experimento, as mucosas de 6 animais dos Grupos I e II foram removidas para avaliação histopatológica. A partir de fotografias tiradas diariamente, a mucosite foi classificada clinicamente. O teste de Mann-Whitney demonstrou haver diferenças estatisticamente significantes (p<0,05) entre o grupo tratado com laser e o grupo não tratado quando se comparou, clinica e histopatologicamente, a intensidade da mucosite induzida. Concluiu-se que a aplicação do laser de baixa intensidade, nos parâmetros determinados para este estudo, promoveu a redução... (Resumo completo, clicar acesso eletrônico abaixo). / Abstract: Toxic and dose-limiting effects of antineoplastic agents in oral cavity are frequently observed during cancer therapy. The available therapies are not able to destroy tumor cells without causing damage to the rapid dividing cells in normal tissues like the epithelial cells in the oral mucosa. Mucositis is the most debilitating side effect, for which there is no established treatment. This oral complication restricts intake of food and liquids, causes discomfort, severe pain and may determine interruption of the cancer therapy, interfering on the disease control. Considering the clinical significance of mucositis, it is important to find ways to treat this condition. The present study was conducted to evaluate the laser therapy effects on prevention or reduction of chemotherapy-induced mucositis in hamsters. Mucositis was induced in 60 animals with intraperitoneal injections of 5-fluorouracil (5-FU) on days 0 and 2, associated with cheek pouches scarification on days 3 and 4. Thirty animals (Group I) received laser irradiation at five points in each cheek pouch, for seven consecutives days. Laser parameters were set to 685 nm, 12 J/cm2 and 30 mW. Other 30 animals (Group II) received no treatment. In Group III, 5 animals represented the baseline control. The cheek pouches of 6 animals from Groups I and II were dissected for histophatological examination on days 0, 4, 8, 12, and 15. Daily photographs were taken and mucositis was clinically scored. The nonparametric test of Mann-Whitney showed statistical difference between treated and nontreated group (p<0.05). It was concluded that the low intensity laser therapy protocol established for this study reduced the severity of oral mucositis and accelerated the healing process, although it has not prevented the appearance of oral manifestations. / Orientador: Fabio César Braga de Abreu e Lima / Coorientador: Carlos Alberto de Souza Costa / Banca: Elaine Maria Sgavioli Massucato / Banca: Luciane Almeida Lopes / Mestre

Cardiovascular disease (CVD) is a major health problem in developed countries and, with increasing prevalence in developing countries and Eastern Europe. Due to the increased incidence with advancing age, there is a need to develop primary preventive interventions to prolong the period of healthy life. Diet has a substantial influence on health and aging. The composition of the human diet plays an important role in the management of lipid and lipoprotein. In this respect, we have focused on the effects of two kinds of functional foods, tea seed oil and dietary onion on their hypocholesterolemic activities and underlying mechanisms in the present study. / Clearly, there are many claims on health benefits of Alliums , however, most, with the exception of garlic, have not received any rigorous or even gentle scientific investigation. Thus, the present study was carried out to explore hypocholesterolemic effects of onion supplementation. After fed for 2 weeks of the high fat high cholesterol diet, thirty-six 8-week male hamsters were divided into four groups. Control group was continued fed with high fat high cholesterol diet, while the other two experimental groups were fed control diet plus 1% (1OP) and 5% (5OP) onion powder for 8 weeks. It was found that feeding high dose of onion powder diet significantly prevented the increase in serum TC, Non-HDL-C and the ratio of non-HDL-C/HDL respectively in hamsters fed a 0.1% cholesterol diet. In contrast, the ratio of HDL/TC in high dose group was significantly increased than that in the control. Low onion dose group tended to have the similar effects as high dose group but, statistically, no difference was observed between the control and low dose groups. Besides, both doses of onion powder diets could significantly countered the increase in serum TG levels. High dose of onion supplementation tended to increase output of fecal neutral and acidic sterols, resulting in reduction of cholesterol retained and absorption. High dose of onion powder diet could significantly up- regulate SREBP-2, LXRbeta, and CYP7A1 protein expressions. The hypocholesterolemic activities of onion might due to the richness in alkyl and alkenyl sulfoxide compounds, anthocyanin, quercetin and cycloalliin, all of which have therapeutic effects. / In conclusion, diet plays an important role in reducing the risk of CVD. This has led to the search for specific foods and food components that may help to improve the serum lipoprotein profile. In present study, tea seed oil and onion was proved to help favorably modify the plasma lipoprotein profile, serving as health supplementation. However, their potential mechanisms were not fully studied and need to be further explored. / Interest in tea seed oil (named tea oil) as a cooking oil is increasing. However, its effect on blood cholesterol is not known. This study was therefore conducted to compare the hypocholesterolemic activity of tea oil with grape seed, canola and corn oils. Fifty 8-week-old male hamsters were first fed a high fat diet (5% lard), and supplemented with 0.1% cholesterol for 2 weeks and then divided into five groups. Control group was continuously fed high fat high cholesterol diet, while the experimental groups were fed high fat, high cholesterol diet plus 10% tea oil, grape seed oil, canola oil and corn oil for 12 weeks. Results showed that plasma total cholesterol (TC), non-HDL-cholesterol (non-HDL-C) and triacylglycerols (TG) in hamsters fed a 0.1% cholesterol diet containing tea, grape, canola or corn oil was significantly reduced compared with those in lard-fed group. Tea oil decreased only non-HDL-C and had no or little effect on HDL-C concentration, while grape oil reduced both. Besides, tea oil-fed hamsters excreted less neutral but greater acidic sterols compared with other three oils. Unlike grape oil, tea oil up-regulated sterol regulatory element binding protein (SREBP-2) and LDL receptor. Differences between tea oil and the tested vegetable oils could be attributable partially to >80% oleic acid in tea oil. / Guan, Lei. / Adviser: Chung Hau Yin. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 98-125). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.