表題番号：2013A-6361
日付：2014/03/06
研究課題ガーリックの含硫化合物成分摂取によるラットの生体防御機能の亜急性応答と生理的役割
| 研究者所属（当時） | 資格 | 氏名 | |
|---|---|---|---|
| （代表者） | 人間科学学術院 | 教授 | 今泉 和彦 |
- 研究成果概要
1. Dose-dependent effects of diallyl disulfide on the number of lymphocyte subsets in rats
Diallyl disulfide (DADS) is a major sulfur compound of garlic, and exerts antiinflamatory, immune-modulatory, and
enhancing sympathetic activity effects. However, it still remains unclear how DADS affects the distribution of white blood cell subsets, which is essential to execute effective immune responses and partially regulated by adrenal glucocorticoids. In the first paper, therefore, we examined the dose-dependent effects of DADS administration on the circulating number of white blood cells (WBCs) and lymphocyte subsets, and plasma corticosterone concentration in rats. Male 10-week-old Sprague-Dawley rats were divided into the DADS-free and DADS-orally administered (dose=10, 20, and 40mg/kg BW) groups. Blood samples were collected from the tail vein at 0, 1, 2, 4 and 6 hour after the administration. DADS administration decreased dose- and time-dependently the circulating number of total WBCs, total lymphocytes, and monocytes. Within the lymphocyte subsets, the circulating number of T-lymphocytes and B-lymphocytes was significantly reduced 4 hour after DADS administration in a dose-dependent manner, although that of natural killer (NK) cells was not affected. On the other hand, although DADS administration did not significantly change the circulating number of neurtophils, the circulating number of eosinophils and basophils showed a decreasing tendency after DADS administration. In contrast, plasma coriticosterone concentration was increased 2 hour after DADS administration in a dose-dependent manner. These results suggest that DADS administration reduces the circulating number of monocytes and lymphocytes, including especially acquired cells, via the action of corticosterone, and the effects are induced in a dose-dependent manner.
2. Dose-dependent effects of diallyl disulfide on plasma glucose and free fatty acid concentrations in rats
In the first paper, we demonstrated that oral administration of DADS (dose=10-40mg/kg BW), the major
organosulfur compound of garlic, reduced the circulating number of monocytes and B- and T-lymphocytes in a dose-dependent manner via the action of corticosterone in adult rats. Glucocorticoid action as well as enhanced sympathetic nerve activity can mobilize energy substrates such as glucose and free fatty acid (FFA) into the blood by inducing glycogenolysis and gluconeogenesis in the liver and lipolysis. However, there is a little information on the effects of DADS intake on lipolysis and carbohydrate metabolism. In the second paper, therefore, we examined the dose-dependent responses of plasma glucose and FFA concentrations, in adult rats after oral administration of DADS. We also measured gastric contents as an index of impaired gastric function. Male 10-week-old Sprague-Dawley rats were divided into DADS-free and DADS-administered (dose=10, 20, and 40mg/kg BW) groups. Plasma samples were prepared from whole blood drawn from the tail vein 0, 1, 2, 4 and 6 hour after administration. The stomachs were isolated, and the contents were measured 8 hour after administration. In DADS-administered groups, plasma glucose concentrations were increased in a dose-dependent manner 1 hr after the administration. The increase was transient, except in groups administered 40mg/kg BW of DADS, in which plasma glucose levels remained significantly higher than the DADS-free levels throughout the experimental period. Similar patterns were observed in the plasma FFA concentrations. The gastric contents were dose-dependently elevated after DADS administration. The increase was significant when 20 or 40mg/kg BW of DADS was administered. These results suggest that oral administration of DADS can mobilize energy substrates into the blood, although a higher dose of DADS slows gastric emptying.
3. Diallyl disulfide accumulates the number of B-lymphocytes in the rat spleen
In the first paper, we demonstrated that diallyl disulfide (DADS), the major organosulfur compound in garlic, reduced the number T-lymphocytes, B-lymphocyte, and monocytes via activation of the hypothalamus-pituitary- adrenal axis. However, the translocation of these cells that migrate to in responses to DADS administration is still unclear. In the third paper, therefore, we examined the effects of DADS administration on a number of lymphocyte subsets and monocytes-derived cells including macrophages (monocytes/macrophages) in spleen, the largest secondary lymphonoid organ. Male 10-week-old Sprague-Dawley rats were orally administered with DADS (dose=20mg/kg BW) or equivalent volume of vehicle. The spleen was harvested 4 hour after administration, and then the splenic cells were isolated, and the total number of cells was counted. T-lymphocytes, B-lymphocytes, natural killer (NK) cells, and monocytes/macrophages were fractionated by flow-cytometry and the total number of these cells was calculated. The total number of splenic cells was significantly increased by 1.18-fold after DADS administration. Among the lymphocyte subsets in the spleen, the number of B-lymphocytes was significantly increased by 1.28-fold after DADS administration. The number of T-lymphocytes also showed a tendency to increase. However, the number of NK cells, and monocytes/macrophages did not change after DADS administration. These results suggest that B-lymphocytes migrate from the circulation and translocate to the spleen in response to DADS administration.