Genistein과 Daidzein 급여가 제2형 당뇨동물모델의 적혈구와 조직 중의 항산화방어계에 미치는 영향

국문 초록 (Abstract)

제2형 당뇨 동물모델(C57BL/KsJ-db/db)을 대상으로 대두 이소플라본의 주성분인 genistein과 daidzein의 항산화효능을 검증하고자 5주령의 수컷 C57BL/KsJ-db/db 마우스와 그의 이형접합체인 C57BL/KsJ-db/+ 마우스를 2주간 환경에 적응시킨 후 비당뇨군(db/+), 당뇨대조군(db/db), genistein 급여군(db/db-genistein), daidzein 급여군(db/dbdaidzein)으로 나누어 6주간 사육하였다. 실험동물의 간, 부고환지방과 신주변지방의 조직무게는 당뇨군(db/db)이 비당뇨군(db/+)에 비해 유의적으로 높았으나, 심장무게는 유의적으로 낮았다. Genistein과 daidzein 급여는 장기무게 변화에 영향을 미치지 않았다. 적혈구의 SOD와 CAT활성은 혈당과 양의 상관성을 보였으나 GSH-Px활성은 음의 상관성을 나타내었다. 따라서 SOD와 CAT활성은 db/db군이 db/+군에 비해 유의적으로 높은 반면, GSH-Px 활성은 유의적으로 낮았다. Genistein과 daidzein 급여로 db/db군의 증가된 CAT활성은 감소되었으며 GSH-Px활성은 높게 나타났다. 적혈구의 GSH함량은 당뇨군들이 비당뇨군에 비해 유의적으로 높았으나 genistein과 daidzein에 의한 영향은 관찰되지 않았다. 간, 신장 및 심장조직 내 SOD활성은 유의적인 변화가 없었으나 간조직 중 CAT와 GSH-Px활성과 신장조직 중의 GSH-Px활성은 db/db군이 db/+군에 비하여 유의적으로 높게 나타난 반면 신장조직 중의 CAT활성과 심장조직 중의 CAT와 GSH-Px활성은 낮았다. 그러나 genistein과 daidzein 급여는 고혈당으로 인한 조직 내 CAT와 GSH- Px활성을 유의적으로 개선하였다. 적혈구를 비롯하여 모든 조직 내 지질과산화물 함량은 db/db군이 db/+군에 비하여 유의적으로 높았으나 genistein과 daidzein 급여로 간, 신장과 심장조직 중의 지질과산화물 생성이 유의적으로 억제되었다. 이와 같이 genistein과 daidzein은 제2형 당뇨동물에서 고혈당으로 야기되는 적혈구와 조직 내 항산화효소 변화를 완화하고 간, 신장 및 심장조직의 지질과산화물을 낮추는 것으로 관찰됨으로써 이들의 항산화작용을 통한 당뇨 합병증을 예방할 것으로 사료된다.

다국어 초록 (Multilingual Abstract)

Our preliminary study showed that genistein and daidzein improved blood glucose level in type 2 diabetic mice by enhancing the glucose and lipid metabolism. The objective of this study was to evaluate whether genistein and daidzein are associated with alterations in antioxidant defense mechanism of type 2 diabetic mice. Male C57BL/KsJ-db/db (db/db) mice and age-matched non-diabetic littermates (db/+) were used in this study. The db/db mice were divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups. The relative weights of liver, epididymal adipose tissue and perirenal adipose tissue were significantly higher in the db/db group than in the db/+ group, whereas heart weight was lower. The genistein and daidzein supplement did not affect the organ weights in db/db mice. The blood glucose level was positively correlated with superoxide dismutase (SOD, r=0.380, p＜0.05) and catalase (CAT, r=0.345, p＜0.05) activities and negatively correlated with glutathione peroxidase (GSH-Px, r=-0.404, p＜0.05) activity in erythrocyte. Therefore, the erythrocyte SOD and CAT activities were significantly elevated in the db/db group compared to the db/+ group and the GSH-Px activity was lowered. However, the supplementation of genistein and daidzein reversed erythrocyte CAT and GSH-Px activities in type 2 diabetic mice. In this current study, the SOD activities in liver, kidney and heart were significantly not different between the groups. The CAT and GSH-Px activities in liver and GSH-Px activity in kidney were significantly higher in the db/db group than in the db/+ group, while the CAT activity in kidney, CAT and GSH-Px activities in heart were lowered. The supplementation of genistein and daidzein significantly attenuated the changes of CAT and/or GSH-Px activities in liver and heart. The supplementation of genistein and daidzein elevated GSH levels in kidney and heart compared to the db/db control group. The lipid peroxide levels in liver, kidney and heart were significantly lowered in the genistein and daidzein supplemented groups compared to the db/db control group. These results suggest that genistein and daidzein might be beneficial for the prevention of type 2 diabetic complication via suppressing changes of antioxidant enzymes activities with simultaneous reduction of lipid peroxidation.

목차 (Table of Contents)

• Abstract
• 서론
• 재료 및 방법
• 결과 및 고찰
• 요약
• 감사의 글
• 문헌

참고문헌 (Reference)

1 "an enzymatic function for erythrocuperine" 6049-6055, 1969

2 "Zinc and the diabetic heart" 18 : 325-332, 2005

3 "Tissue sulfhydryl groups" 82 : 70-77, 1959

4 "The usual intake of lignans but not that of isoflavones may be related to cardiovascular risk factors in U.S. men" 135 : 260-266, 2005

5 "The therapeutic potential of phytoestrogens" 9 : 1829-1840, 2000

6 "Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase" 70 : 158-169, 1967

7 "Soy protein and cardiovascular disease: the impact of bioactive components in soy" 56 : 231-235, 1998

8 "Response of glucose metabolism enzymes in an acute porphyria model Role of reactive oxygen species" 216 : 49-58, 2005

9 "Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies" 107 : 1340-1348, 1977

10 "Oxidative stress and nitric oxide related parameters in type ?? diabetes mellitus effects of glycemic control" 34 : 65-70, 2001

11 "Long-term renal effects of a neutralizing RAGE antibody in obese type 2 diabetic mice" 53 : 166-172, 2004

12 "Lipid peroxidation in erythrocytes" 45 : 251-268, 1987

13 "Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase" 47 : 469-474, 1974

14 "In Methods of enzymatic analysis" Academic Press -684, 1974

15 "Hypocholesterolemic effect of soybean and soy products" 5 : 36-41, 2000

16 "High glucose alters cardiomyocyte contacts and inhibits myofibrillar formation" 91 : 1961-1967, 2006

17 "Glomerular macrophages and the mesangial proliferative response in the experimental nephrotic syndrome" 141 : 887-894, 1992

18 "Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice." 79 : 1207-1213, 2006

19 "Food labeling health claims: soy protein and coronary heart disease" 64 : 57700-57733, 1999

20 "Endurance training attenuates exercise- induced oxidative stress in erythrocyte in rat" 91 : 622-627, 2004

21 "Effects on the human serum lipoprotein profile of beta-glucan, soy protein and isoflavones, plant sterols and stanols, garlic and tocotrienols." 132 : 2494-2505, 2002

22 "Effect of vitamin E on the oxidative state of glutathione in plasma" 8 : 140-143, 1990

23 "Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress." 212 : 167-178, 2006

24 "Dehydroepiandrosterone suppresses the elevated hepatic glucose-6- phosphatase and fructose-1,6-bisphosphatase activities in C57BL/KsJ-db/db mice: comparison with troglitazone." 48 : 1579-1585, 1999

25 "Chronic effects of an ┒-glucosidase inhibitor on intestinal disaccharidase activity in normal and diabetic mice" 132-137, 1987

26 "Chemistry of the 2-thiobarbituric acid test for determination of oxidative rancidity in foods" 15 : 602-607, 1964

27 "Cardiac function and metabolism in type 2 diabetic mice after treatment with BM 17.0744, a novel PPAR-alpha activator." 283 : 2002

28 "Beneficial role of dietary phytoestrogens in obesity and diabetes" 76 : 1191-1201, 2002

29 "Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes" 25 : 1709-1714, 2002

30 "Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects" 24 : 228-233, 2001

31 "Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction" 95 : 351-358, 1979

32 "Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy" 36 : 557-562, 2003

33 "Antioxidant status and lipid peroxidation in type ?? diabetes mellitus with and without complications" 90 : 255-260, 1996

34 "Antioxidant defense mechanisms of endothelial cells" 1986

35 "Antioxidant activity of isoflavones and their major metabolites using different in vitro assays" 54 : 2926-2931, 2006

36 "Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice" 52 : 434-441, 2003

37 "Abnormal antioxidant status in impaired glucose tolerance and non insulin-dependent diabetes mellitus" 13 : 715-719, 1996

38 "A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding" 72 : 248-254, 1976