Yang Cha Lee-Kim

Changes in Lipid Peroxidation and Antioxidant Trace Elements in Serum of Women With Cervical Intraepithelial Neoplasia and Invasive Cancer

This study investigated serum lipid peroxidation, antioxidant capacity, and trace element levels in Korean women as related to uterine cervical neoplasia. Twenty-eight subjects had cervical intraepithelial neoplasia (CIN), 36 had invasive cervical cancer, as determined by a colposcopically directed biopsy, and controls included 44 subjects with normal colposcopic findings. Significantly lower selenium (Se) and zinc (Zn) levels and higher copper/Zn ratios were found in both CIN and cancer patients compared with the controls. Serum malondialdehyde levels decreased significantly in the order CIN>cancer>control, implying the involvement of reactive oxygen species at the precancerous stage, that is, prior to progression into invasive cervical cancer. Serum glutathione peroxidase activity was significantly lower in patients with CIN or cancer than controls, and total antioxidant ability decreased from controls to CIN to cancer (P < 0.0001). This study demonstrated the involvement of lipid peroxidation, decreased Se and Zn levels, and an impaired serum antioxidant system in the pathogenesis of cervical dysplasia. Further research is needed to examine the possibility of an effective chemopreventive treatment in cervical cancer based on enhancing the endogenous antioxidant system.

Kale juice improves coronary artery disease risk factors in hypercholesterolemic men.

OBJECTIVE To evaluate the effect of 3-month kale (Brassica oleracea acephala) juice supplementation on coronary artery disease risk factors among hypercholesterolemic men. METHODS Thirty-two men with hypercholesterolemia (> 200 mg/dL) were recruited after annual health examinations among the faculty and staff at university. The subjects consumed 150 mL of kale juice per day for a 12-week intervention period. Dietary and anthropometric assessments were performed and blood samples were collected to evaluate biochemical profiles before and after supplementation. RESULTS Serum concentrations of HDL-cholesterol, and HDL- to LDL-cholesterol ratio were significantly increased by 27% (P<0.0001) and 52% (P<0.0001), respectively. The LDL-cholesterol concentration and the atherogenic index were significantly reduced by 10% (P=0.0007) and 24.2% (P<0.0001), respectively without affecting body mass index, waist and hip circumferences, or nutrient intakes after three months of supplementation. While there was no difference in the concentration of malondialdehyde, significant increase in glutathione peroxidase activity (P=0.0005) were accompanied by a significant increase in the serum selenium level (P=0.0132). It was also found that the responses of these risk factors to kale juice administration were dependent on smoking status. CONCLUSION Regular meals supplementation with kale juice can favorably influence serum lipid profiles and antioxidant systems, and hence contribute to reduce the risks of coronary artery disease in male subjects with hyperlipidemia.

Relationship of serum α-tocopherol, carotenoids and retinol with the risk of breast cancer

Abstract The relationship of serum antioxidant vitamin concentration and the risk of breast cancer was investigated in a case-control study in Korea. This study was carried out with 389 subjects consisting of 160 breast cancer patients and 229 control subjects from June 1994 to July 1995. The serum concentrations of α-tocopherol, carotenoids and retinol were measured simultaneously by a reverse phase, gradient HPLC system. Average serum concentrations of α-tocopherol, β-carotene and retinol were 7.63 ± 0.42 ug/ml, 40.5 ± 2.05 ug/dl, and 49.0 ± 4.10 ug/dl for cases and 11.0 ± 0.73 ug/ml, 48.3 ± 1.59 ug/dl and 64.6 ± 1.95 ug/dl for controls, respectively. Serum levels of α-tocopherol, β-carotene, cryptoxanthin, lutein+zeaxanthin, lycopene and retinol of breast cancer patients were significantly lower than those of controls. Odds ratios (ORs) adjusted for age, body mass index, smoking habit and alcohol drinking revealed a significant gradient of decreasing risk of breast cancer with increasing serum antioxidant vitamins. There were significant interactions between menopausal status and serum levels of antioxidant vitamins. The adjusted odds ratios for highest quintile compared with lowest quintile were 0.41 (95% CI, 0.18, 0.93) for α-tocopherol, 0.33 (95% CI, 0.15, 0.73) for β-carotene, 0.13 (95% CI, 0.06, 0.31) for zeaxanthin+lutein in premenopausal women; 0.13 (95% CI, 0.03, 0.66) for α-tocopherol, 0.28 (95% CI, 0.07, 1.12) for β-carotene, 0.12 (95% CI, 0.03, 0.58) for zeaxanthin+lutein in postmenopausal women. This results support inverse association between serum antioxidant vitamins and the risk of breast cancer in Korea and indicate that antioxidant vitamins may protect against breast cancer.

Effects of retinoic acid isomers on apoptosis and enzymatic antioxidant system in human breast cancer cells.

Retinoic acids (RAs) modulate growth, differentiation, and apoptosis in normal, pre-malignant & malignant cells. In the present study, the effects of RA isomers (all-trans RA, 13-cis RA, and 9-cis RA) on the cell signal transduction of human breast cancer cells have been studied. The relationship between RAs and an enzymatic antioxidant system was also determined. Estrogen-receptor (ER) positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells were treated with different doses of each RA isomers, all-trans RA, 13-cis RA, or 9-cis RA. Treatment of RA isomers inhibited cell viability and induced apoptosis of MCF-7 cells as a result of increased caspase activity in cytoplasm and cytochrome C released from mitochondria. All-trans RA was the most effective RA isomer in both cell growth inhibition and induction of apoptosis in MCF-7 cells. However, no significant effect of RA isomers was observed on the cell growth or apoptosis in ER-negative MDA-MB-231 cells. In addition, activities of antioxidant enzymes such as catalase and glutathione peroxidase were decreased effectively after treatment of RA in MCF-7 cells, whereas SOD activity was rarely affected. Thus, the present data suggest that all-trans RA is the most potential inducer of apoptosis and modulator of antioxidant enzymes among RA isomers in MCF-7 human breast cancer cells.

Micellar phytosterols effectively reduce cholesterol absorption at low doses

Background: The objective of this study was to evaluate the effects of micellar phytosterols on cholesterol absorption in humans. Methods: 24 healthy adults (mean age 37 years, 16 women and 8 men) underwent four cholesterol-absorption tests to compare the effects of micellar phytosterols supplement containing 500, 300, 200 mg phytosterols and placebo on cholesterol absorption in a cross-over design. Individual absorption tests were separated by 2 weeks. Using the single oral isotope method, inhibition of cholesterol absorption was determined by gas-chromatography mass spectrometry measurement of the differences in plasma hexadeuterated cholesterol enrichment 4 days after test meals with or without phytosterols. Each test meal provided 500 kcal and 89 mg cholesterol including 40 mg tracer cholesterol. We used a general linear mixed model with SAS to test the significance of treatment effect. Results: Micellar phytosterols had a significant overall effect on cholesterol absorption (p = 0.0002), reduced cholesterol absorption by 23.3% at a dose of 300 mg phytosterols (p = 0.0004) and by 32.0% at a dose of 500 mg phytosterols (p = 0.0001) compared with the placebo. The effect of 200 mg treatment did not reach statistical significance but there was a tendency (p = 0.052). Conclusion: Water-dispersible, micellar phytosterols reduced cholesterol absorption effectively at very low doses.

Longitudinal study on trace mineral compositions (selenium, zinc, copper, manganese) in Korean human preterm milk.

We measured selenium, zinc, copper and manganese concentrations in the human milk of Korean mothers who gave birth to preterm infants, and compared these measurements with the recommended daily intakes. The samples of human milk were collected postpartum at week-1, -2, -4, -6, -8, and -12, from 67 mothers who gave birth to preterm infants (< 34 weeks, or birth weight < 1.8 kg). All samples were analyzed using atomic absorption spectrophotometry. The concentrations of selenium were 11.8 ± 0.5, 11.4 ± 0.8, 12.7 ± 0.9, 11.4 ± 0.8, 10.8 ± 0.9, and 10.5 ± 1.3 µg/L, zinc were 7.8 ± 0.5, 9.1 ± 0.8, 7.2 ± 0.9, 8.0 ± 0.8, 7.4 ± 0.9, and 6.6 ± 1.2 mg/L, copper were 506 ± 23.6, 489 ± 29.4, 384 ± 33.6, 356 ± 32.9, 303 ± 35.0, and 301 ± 48.0 µg/L and manganese were 133 ± 4.0, 127 ± 6.0, 125 ± 6.0, 123 ± 6.0, 127 ± 6.0, and 108 ± 9.0 µg/L at week-1, -2, -4, -6, -8, and -12, respectively. The concentrations of selenium and zinc meet the daily requirements but that of copper is low and of manganese exceeds daily requirements recommended by the American Academy of Pediatrics, Committee on Nutrition.

Carotenoids and total phenolic contents in plant foods commonly consumed in Korea

Phytochemicals are reported to provide various biological functions leading to the promotion of health as well as the reduced risk of chronic diseases. Fat-soluble plant pigments, carotenoids, are extensively studied micronutrient phytochemicals for their potential health benefits. It is noteworthy that specific carotenoids may be responsible for different protective effects against certain diseases. In addition, each carotenoid can be obtained from different types of plant foods. Considering the fact that the phytochemical content in foods can vary according to, but not limited to, the varieties and culture conditions, it is important to establish a database of phytochemicals in locally produced plant foods. Currently, information on individual carotenoid content in plant foods commonly consumed in Korea is lacking. As the first step to support the production and consumption of sustainable local plant foods, carotenoids and total phenolic contents of plant foods commonly consumed in Korea are presented and their potential biological functions are discussed in this review.

Retinoids, Carotenoids, and Tocopherols in Breast Adipose Tissue and Serum of Benign Breast Disease and Breast Cancer Patients

Various retinoic acid (RA) isomers (all-trans, 13-cis, 11-cis, and 9-cis) as well as retinol, carotenoids, and tocopherol concentrations were determined in both serum and breast adipose tissue of 22 benign breast disease patients and 52 breast cancer patients categorized into 4 stages by malignancy. Serum RA isomers were analyzed by a newly developed sensitive method combining a high-performance liquid chromatography and a gas chromatography-mass spectrometry, and retinol, carotenoid, and tocopherol concentrations using a high-performance liquid chromatography system. The breast cancer patients showed significantly lower serum retinol, whereas significantly higher breast adipose tissue retinol concentration than those of benign breast disease patients. Although breast cancer patients showed significantly higher serum all-trans and 13-cis RA concentrations, 11-cis RA in breast adipose tissue was significantly lower in the breast cancer patients than those of benign breast disease patients and it was associated with the stage of malignancy. The current study indicates that the retinol and RA isomers in the target tissue of breast tumor patients are not reflecting their concentrations in circulation. The mechanisms of tissue specific uptake of RA isomers and their functions warrant further studies.

Serial Changes of Fatty Acids in Preterm Breast Milk of Korean Women

Samples of breast milk were collected at postpartum weeks 1, 2, 4, 6, 8, and 12 from 104 Korean mothers who had delivered infants at less than 34 weeks or weighing less than 1.8 kg to investigate changes in fatty acid (FAs). Full-term breast milk (FBM) collected at the end of first week postpartum from 26 Korean women delivering healthy, term infants was used for comparison. Stability in relative FA composition was maintained during the first 3 months of lactation in preterm breast milk (PBM), and the relative composition of polyunsaturated FAs (PUFA), monounsaturated FAs, and saturated FAs remained constant in PBM. However, the ω6/ω3 ratio was significantly higher as lactation progressed owing to lower ω3 PUFA in PBM. The proportions of docosahexaenoic acid (DHA) and arachidonic acid (AA) in PBM gradually decreased over time, but the DHA/AA ratio was kept constant at 1.13, higher than that of Western countries. At the end of the first week, relative proportions of FAs were similar in PBM and FBM, but absolute concentrations of FA were higher in PBM.

Enhancement of hepatic drug metabolism in 3-week-old pups by maternal feeding of n-3 polyunsaturated fatty acid diets

Abstract The rates of drug oxidation and glucuronidation in the livers of 3-week-old rats that were born to and nursed by pregnant rats fed diets containing either the n-3 or the n-6 fatty acids throughout gestation and lactation were measured. Pregnant rats were fed diets containing 10% fats composed of: (1) beef tallow and corn oil (32.5% n-6 linoleic acid, control group), (2) corn oil (62.4% n-6 linoleic acid, corn oil group), (3) perilla oil (58.3% n-3 linolenic acid, perilla oil group), and (4) fish oil (35.1% n-3 eicosapentaenoic acid and 17.3% n-3 docosahexaenoic acid, fish oil group). The rates of drug oxidation (ethoxycoumarin O-deethylation) and glucuronidation (glucuronide conjugation of hydroxycoumarin), the reactions carried out by enzymes present in microsomal membranes, were determined by employing the isolated perfused liver system. While the contents of cytochromes P-450 and b5 were not increased, the determined rates of drug oxidation were significantly higher for the pups of n-3 and n-6 fatty acid diet groups than those of the control group. The rates of both drug oxidation and glucuronidation observed for the n-3 fatty acid diet groups (perilla and fish oil) were higher than those of the n-6 fatty acid diet groups (control and corn oil). In particular, the highest rates of drug oxidation and glucuronidation were observed with the pups of fish oil diet group. The fatty acid compositions of offspring liver microsomes were influenced by the composition present in maternal diets. The n-3 and n-6 fatty acid components in maternal diet converted to their own series of longer polyunsaturated fatty acids and were substitutively incorporated into phospholipids of liver microsomal membranes in 3-week-old rats. Thus, it appeared that the hepatic microsomal drug metabolizing enzymes operated more efficiently when the proportion of n-3 polyunsaturated fatty acid in microsomal membrane phospholipid was increased. However, when the polyunsaturated/monounsaturated/saturated (P/M/S) ratios and double bond indices (an indicator of membrane fluidity) were calculated from the fatty acid composition of 3-week-old rat liver microsomes, although the P/M/S ratios maintained constant values in all groups, the double bond indices of corn, perilla, and fish oil diet groups increased in order. Furthermore, the degree of increases of double bond indices coincided with the increments of the hepatic drug oxidation rate. Therefore, it is concluded that the higher degree of unsaturation rather than the specific kinds (n-3 or n-6) of polyunsaturated fatty acids present in liver microsomal membranes is responsible for the observed increases in the rates of drug metabolism.