Hiroko Negishi

Antioxidant nutrients and hypoxia/ischemia brain injury in rodents

Cerebral ischemia and recirculation cause delayed neuronal death in rodents, such as Mongolian gerbils and stroke-prone spontaneously hypertensive rats (SHRSP), which were used as an experimental stroke model. It was documented that an enhanced nitric oxide production, the occurrence of apoptosis, and an attenuated redox regulatory system contribute to the development of delayed neuronal death. Many studies have suggested the beneficial antioxidant effects of antioxidant nutrients such as vitamin E, green tea extract, ginkgo biloba extract, resveratrol and niacin in cerebral ischemia and recirculation brain injury. These results are important in light of an attenuation of the deleterious consequences of oxidative stress in ischemia and recirculation injury.

Cardiovascular risk factors in Tanzania: a revisit

In this assessment of cardiovascular risk factors, we examined the prevalence of selected risk factors according to the World Health Organisation (WHO) CARDIAC Study protocol and compared them with a similar study conducted more than a decade ago. The survey was carried out in Dar es Salaam (D, urban), Handeni (H, rural) and Monduli (Mo, semi-nomadic area). Subjects aged 47-57 were recruited randomly for blood pressure and anthropometrical measurements, 24 h urine collection and blood sampling. A structured questionnaire was used to obtain dietary information. The 1998 survey studied 446 subjects, while the 1987 survey included 496 men and women. The measured weight, body mass index (BMI) and prevalence of obesity (BMI > or = 30 kg/m(2)) increased significantly among women in the 1998 survey in rural Handeni and urban Dar. The overall prevalence of obesity was higher for women in the most recent survey (22.8%, P < 0.0001). Diastolic blood pressure (DBP) was higher in the most recent survey for women in Handeni. The overall prevalence of hypertension (blood pressure > 160/95 mmHg, or antihypertensive drug use), rose to 41.1% in 1998, (P < 0.001) for men and to 38.7% (P < 0.05) for women. The mean total serum cholesterol and prevalence of hypercholesterolaemia increased significantly in the most recent survey in the three studied areas. The overall prevalence of hypercholestrolaemia (serum cholesterol > 5.2 mmol/l) was higher in the 1998 survey for both men (21.8%, P < 0.0001) and women (54.0%, P < 0.0001). The mean HDL cholesterol increased significantly in the most recent survey, with a significant reduction in the mean atherogenic index, though these were still at higher levels (men 5.8, P < 0.0001; women 5.1, P < 0.0001 vs. 1987). A strong positive correlation was observed between blood pressure (SBP and DBP) and body mass index, total serum cholesterol and sodium to potassium ratio. These data suggest that for the past decade there has been an increase in the mean levels and prevalence of selected cardiovascular risk factors in Tanzania.

Effect of Undaria pinnatifida (Wakame) on the development of cerebrovascular diseases in stroke-prone spontaneously hypertensive rats.

1. We showed that a nutritional factor was able to attenuate the development of hypertension and its related diseases in stroke‐prone spontaneously hypertensive rats (SHRSP). In the present study, the effect of Wakame, an edible brown seaweed, on the development of stroke was examined in SHRSP.

The relation of oxidative DNA damage to hypertension and other cardiovascular risk factors in Tanzania.

Objectives To clarify the mechanism of involvement of oxidative stress in hypertensives, we investigated the relationship between the marker of oxidative DNA damage, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), and cardiovascular risk factors, such as hypertension and serum glycosylated hemoglobin (HbA1c), among Tanzanians aged 46–58 years who were not on antihypertensive medication. Design and methods Sixty subjects (males/females, 28/32) were selected randomly from the subjects who completed a 24h urine collection in our epidemiological study at Dar es Salaam, Tanzania in 1998. The subjects were divided into two groups, hypertensive subjects (systolic blood pressure (SBP) ⩾ 140 mmHg and/or diastolic blood pressure (DBP) ⩾90 mmHg) and normotensive subjects (SBP <140 mmHg and DBP <90 mmHg) or hyperglycemic subjects (HbA1c ⩾ 6.0%) and normoglycemic subjects (HbA1c< 6.0%). Biological markers from urine and blood were analyzed centrally in the WHO Collaborating Center. Results The mean levels of HbA1c and 8-OHdG were significantly higher in the hypertensive subjects than in the normotensive subjects (P < 0.05). Urinary 8-OHdG was significantly higher in hyperglycemic subjects than in normoglycemic subjects. HbA1c was positively correlated with the 24-h urinary 8-OHdG excretions (r = 0.698, P < 0.0001). Conclusions These findings suggest oxidative DNA damage is increased in hypertensive subjects, and there is a positive correlation between the level of blood glucose estimated as HbA1c and oxidative DNA damage. Hyperglycemia related to insulin resistance in hypertension in Tanzania is associated with increased urinary 8-OHdG.

INCREASED OXIDATIVE DNA DAMAGE IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

1. The amount of urinary 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), a biomarker of the total systemic oxidative stress in vivo, in stroke‐prone spontaneously hypertensive rats (SHRSP) was not different from that in control normotensive Wistar‐Kyoto (WKY) rats at 6 weeks of age, but became higher than control values after the development of severe hypertension at 14–17 weeks of age.

SERUM LIPID EFFECTS OF A MONOUNSATURATED (PALMITOLEIC) FATTY ACID-RICH DIET BASED ON MACADAMIA NUTS IN HEALTHY, YOUNG JAPANESE WOMEN

1. Recent studies have identified potential beneficial effects of eating nuts, most of which have substantial amounts of monounsaturated fatty acids (MUFA). Macadamia nuts consist of 75% fat by weight, 80% of which is MUFA (palmitoleic acid).

Increased hydroxyl radicals in the hippocampus of stroke-prone spontaneously hypertensive rats during transient ischemia and recirculation

It has been suggested that stroke-prone spontaneously hypertensive rats (SHRSP) show vulnerability to neuronal damage following transient ischemia. To observe the effect of hydroxyl radicals on neuronal damage in the hippocampus of SHRSP during ischemia and recirculation, we measured the levels of 2,3-dihydroxybenzoic acid (2,3-DHBA), as a biological marker of hydroxyl radicals in the hippocampus of SHRSP, by high pressure liquid chromatography-electrochemical detection. The production of hydroxyl radicals in the hippocampus during the first 20 min of recirculation was a peak in all intervals. The changes in 2,3-DHBA levels during ischemia and recirculation in SHRSP were significantly higher than in Wistar-Kyoto rats. These results suggest that neuronal damage following ischemia and recirculation is, in part, caused by the increase in hydroxyl radicals during ischemia and recirculation.

EFFECTS OF PRUNE EXTRACT ON BLOOD PRESSURE ELEVATION IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

1 Prunes are recognized as a health food. They contain large amounts of phenolics and show high anti‐oxidant activity. In this study, both hydroxyl radicals and superoxide anion were scavenged by prune extract in electron spin resonance (ESR) analysis. 2 In angiotensin II challenged vascular smooth muscle cells (VSMCs) from stroke‐prone spontaneously hypertensive rats (SHRSP), the reactive oxygen species (ROS) level was decreased in caffeic acid‐treated cells compared with the control. 3 After 5 weeks of prune extract treatment, the elevation of blood pressure in the prune extract‐treated SHRSP was suppressed in comparison with the control group. 4 Our findings suggest that prune extract may contribute to the primary prevention of cardiovascular diseases.

ISOFLAVONE AGLYCONES PROMOTE THE mRNA EXPRESSION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE IN AORTA AND REDUCED BLOOD PRESSURE IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS

1 The aim of the present study was to assess the effects of isoflavone aglycones (IFA; AglyMaxTM; Nichimo Co. Ltd, Tokyo, Japan), containing 32.9% IFA, on the production of nitric oxide (NO) and systolic blood pressure (SBP) in stroke‐prone spontaneously hypertensive rats (SHRSP). 2 Twelve male SHRSP rats, aged 5 weeks, were used. Rats were divided into two groups: (i) the IFA group (n = 6); and (ii) the control group (n = 6). Administration of IFA (20 mg/kg equivalent of isoflavones) resulted in a significant decrease in SBP in the IFA‐treated group compared with the control group. 3 Nitric oxide levels in the urine and serum were also significantly higher in the IFA‐treated group than in the control group. Significantly higher levels of endothelial NO synthase mRNA were also confirmed in the IFA group compared with the control group. 4 Isoflavone aglycones could decrease SBP significantly by increasing the formation of NO.

Estimation of Hydroxyl Radicals Based on the Salicylate Trapping Method in Hippocampus of Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) During Transient Ischemia and Recirculation

Neuronal damage following transient cerebral ischemia is mediated by various mechanisms, among which oxygen radical-mediated processes play a central role. Ischemia and subsequent recirculation provide circumstances that favor their production. Free radicals are extremely reactive compounds that can interact with lipids, enzymes and DNA to produce various harmful effects. Several reports have suggested that hippocampal neurons in Stroke-prone Spontaneously Hypertensive rats (SHRSP) which are regarded as model animals for ischemic stroke in humans, were innately more vulnerable to ischemic damage than in the mother strain of SHRSP, Wistar Kyoto rats (WKY). In a previous study, we demonstrated the important role of free radicals in the development of neuronal damage in the hippocampus of SHRSP subjected to cerebral ischemia and reperfusion. However, direct evidence of hydroxyl radicals, which are very reactive and readily react with a number of compounds, in the course of cerebral ischemia and reperfusion in SHRSP has not been obtained.