Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats

Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg−1 d−1), Agaricus blazei (1 g kg−1 d−1) or Smallanthus sonchifolius (4 g kg−1 d−1) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic β-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic β-cells mass

Study on Application of Static Magnetic Field for Adjuvant Arthritis Rats

In order to examine the effectiveness of the application of static magnetic field (SMF) on pain relief, we performed a study on rats with adjuvant arthritis (AA). Sixty female Sprague–Dawley (SD) rats (age: 6 weeks, body weight: approximately 160 g) were divided into three groups [SMF-treated AA rats (Group I), non-SMF-treated AA rats (Group II) and control rats (Group III)]. The SD rats were injected in the left hind leg with 0.6 mg/0.05 ml Mycobacterium butyrium to induce AA. The rats were bred for 6 months as chronic pain model. Thereafter, the AA rats were or were not exposed to SMF for 12 weeks. We assessed the changes in the tail surface temperature, locomotor activity, serum inflammatory marker and bone mineral density (BMD) using thermography, a metabolism measuring system and the dual-energy X-ray absorptiometry (DEXA) method, respectively. The tail surface temperature, locomotor activity and femoral BMD of the SMF-exposed AA rats were significantly higher than those of the non-SMF-exposed AA rats, and the serum inflammatory marker was significantly lower. These findings suggest that the pain relief effects are primarily due to the increased blood circulation caused by the rise in the tail surface temperature. Moreover, the pain relief effects increased with activity and BMD of the AA rats

Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK) and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF) with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS) and inducible/constitutive heme oxygenase (HO-1/HO-2) in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity in vitro enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK

In Vivo Diagnostic Imaging Using Micro-CT: Sequential and Comparative Evaluation of Rodent Models for Hepatic/Brain Ischemia and Stroke

BACKGROUND: There is an increasing need for animal disease models for pathophysiological research and efficient drug screening. However, one of the technical barriers to the effective use of the models is the difficulty of non-invasive and sequential monitoring of the same animals. Micro-CT is a powerful tool for serial diagnostic imaging of animal models. However, soft tissue contrast resolution, particularly in the brain, is insufficient for detailed analysis, unlike the current applications of CT in the clinical arena. We address the soft tissue contrast resolution issue in this report. METHODOLOGY: We performed contrast-enhanced CT (CECT) on mouse models of experimental cerebral infarction and hepatic ischemia. Pathological changes in each lesion were quantified for two weeks by measuring the lesion volume or the ratio of high attenuation area (%HAA), indicative of increased vascular permeability. We also compared brain images of stroke rats and ischemic mice acquired with micro-CT to those acquired with 11.7-T micro-MRI. Histopathological analysis was performed to confirm the diagnosis by CECT. PRINCIPAL FINDINGS: In the models of cerebral infarction, vascular permeability was increased from three days through one week after surgical initiation, which was also confirmed by Evans blue dye leakage. Measurement of volume and %HAA of the liver lesions demonstrated differences in the recovery process between mice with distinct genetic backgrounds. Comparison of CT and MR images acquired from the same stroke rats or ischemic mice indicated that accuracy of volumetric measurement, as well as spatial and contrast resolutions of CT images, was comparable to that obtained with MRI. The imaging results were also consistent with the histological data. CONCLUSIONS: This study demonstrates that the CECT scanning method is useful in rodents for both quantitative and qualitative evaluations of pathologic lesions in tissues/organs including the brain, and is also suitable for longitudinal observation of the same animals

Immunohistochemical analysis of brain lesions using S100B and glial fibrillary acidic protein antibodies in arundic acid- (ONO-2506) treated stroke-prone spontaneously hypertensive rats

Stroke-prone spontaneously hypertensive rats (SHRSP) used as a model of essential hypertension cause a high incidence of brain stroke on the course of hypertension. Incidences and sizes of brain lesions are known to relate to the astrocyte activities. Therefore, relation between brain damage and the expression profile of the astrocytes was investigated with morphometric and immunohistochemical analyses using astrocyte marker antibodies of S100B and glial fibrillary acidic protein (GFAP) with or without arundic acid administration, a suppressor on the activation of astrocytes. Arundic acid extended the average life span of SHRSP. An increase in brain tissue weight was inhibited concomitant with a lower rate of gliosis/hemosiderin deposit/scarring in brain lesions. S100B- or GFAP-positive dot and filamentous structures were decreased in arundic acid-treated SHRSP, and this effect was most pronounced in the cerebral cortex, white matter, and pons, and less so in the hippocampus, diencephalon, midbrain, and cerebellum. Blood pressure decreased after administration of arundic acid in the high-dose group (100 mg/kg/day arundic acid), but not in the low-dose group (30 mg/kg/day). These data indicate that arundic acid can prevent hypertension-induced stroke, and may inhibit the enlargement of the stroke lesion by preventing the inflammatory changes caused by overproduction of the S100B protein in the astrocytes

脳卒中易発症性高血圧自然発症ラットの血小板および動脈硬化に及ぼすスカベンジャーの影響

[SYNOPSIS] In recent years, continuous intake of high fat diet in daily life has been reported to be an etiological factor in life habit—associated diseases. Arteriosclerosis related to high fat diet has been suggested. It is generally known that hypertension is a factor in stimulating arteriosclerosis. In the sclerotic arterial wall, ulcer occurs and induces platelet deposition, causing vasoconstrictors and activating the blood coagulation system. Thus inducing thrombus formation. In this study, we examined the effects of a scavenger (2-Aminomethy1-4-tert-buty1-6-propiony1 phenol hydrochloride : ATPH), which promotes platelet aggregation without influencing cycloxygenase, inhibits TXA_2 synthesis, and exhibits potent anti-inflammatory actions, on platelet aggregation in vitro and in vivo with respect to the synthesis of prostaglandin I_2 (PGI_2) with inhibitory effects on platelet aggregation. Using stroke-prone spontaneously hypertensive rats (SHRSP), we investigated the effects of the scavenger on arteriosclerosis and blood pressure. The following results were obtained. This study was conducted to develop and produce a diet for patients with life habit-associated diseases and elderly people. 1. ATPH inhibited platelet aggregation in a dose-dependent manner in vitro and in vivo. 2. Long-term administration of ATPH did not markedly inhibit platelet aggregation, but markedly inhibited arteriosclerosis, cardiac hypertrophy, and cerebral edema, showing marked life-prolonging effects. 3. These results suggest that this agent prevents arteriosclerosis. 4. Our findings suggest that ATPH can be utilized together with artificialdigestive enzymes for producing a diet for patients with life habit-associated diseases and elderly people, and that ATPH may be effective. 　（要旨）　近年、食生活における高脂肪食の継続摂取が生活習慣病の一因とされ、高脂肪食による動脈硬化が指摘され、高血圧は動脈硬化を誘発・促進する因子であることや硬化動脈壁では潰瘍を生じ、血小板などが沈着するために血管収縮作用を生じ、血液凝固系を促進させて血栓を誘発し、動脈内腔の閉塞により脳梗塞や心筋梗塞を誘発することが知られている。　 本報では、血小板凝集抑制性作用を有するプロスタグラジンI_2（PGI_2）の合成に関し、cycloxygenaseに無影響で血小板凝集促進作用を有し、TXA_2の合成を阻害するとともに強い抗炎症作用を有するスカベンジャー（2-aminomethyl-4-tert-butyl-6-propionyl phenol hydroclocide : ATPH)を用いて、血小板凝集能に対する影響を in vitro 及び in vivo で観察し、脳卒中易発症性高血圧自然発症ラット（SHRSP）を用いて、動脈硬化の改善と血圧に対する影響を検討し、次の結果を得た。　なお、本研究は生活習慣病及び高齢者治療食米飯の製造、開発の基礎として実施した。 1. ATPHの血小板凝集能の抑制効果は、in vitro、in vivo の何れにおいても濃度依存性を示した。　 2. ATPHの長期投与では、血小板凝集能の抑制効果は著名でないが、動脈硬化、心肥大、脳腫瘍を顕著に抑制し、著しい延命効果を示した。　 3. 上記の結果より、本薬物は動脈硬化の予防効果を有することが認められた。　 4. 以上の結果より、ATPHは生活習慣病及び高齢者治療食米飯製造での、人工消化酵素とともに利用が可能であり、有効性が期待されることが示唆された