Are Free Radicals Involved in the Pathobiology of Human Essential Hypertension?

Possible involvement of reactive oxygen species and nitric oxide in the pathogenesis of human essential hypertension was investigated. It was observed that both superoxide anion and hydrogen peroxide production by polymorphonuclear leukocytes and the plasma levels of lipid peroxides are higher in uncontrolled essential hypertension compared with normal controls. Nitric oxide levels measured as its stable metabolite nitrite, as an index of nitric oxide synthesis, revealed its levels to be low in hypertensive patients. Superoxide anion, hydrogen peroxide, lipid peroxides and nitric oxide levels reverted to normal values after the control of hypertension by drugs. The concentrations of anti-oxidants such as vitamin E and superoxide dismutase were found to be decreased in patients with uncontrolled hypertension. Several anti-hypertensive drugs inhibited lipid peroxidation in vitro. Angiotensin-II, a potent vasoconstrictor, stimulated free radical generation in normal leukocytes which could be blocked by calmodulin antagonists. These results suggest that an increase in free radical generation and a simultaneous decrease in the production of nitric oxide and anti-oxidants such as SOD and vitamin E occurs in essential hypertension. This increase in free radical generation can inactivate prostacyclin and nitric oxide and decrease their half life which can lead to an increase in peripheral vascular resistance and hypertension.     

Reactive oxygen species and melanoma: an explanation for gender differences in survival?

Epidemiological research consistently shows a female advantage in melanoma survival. So far, no definite candidate for the explanation of this phenomenon has emerged. We propose that gender differences in oxidative stress caused by radical oxygen species (ROS) underlie these survival differences. It is known that males express lower amounts of anti-oxidant enzymes, resulting in more oxidative stress than females. The primary melanoma environment is characterized by high ROS levels, from exogenous sources as well as ROS production within melanoma cells themselves. ROS are known to be able to promote metastasis through a wide variety of mechanisms. We hypothesize that the higher levels of ROS in men enhance selection of ROS-resistance in melanoma cells. Subsequently, ROS can stimulate the metastatic potential of melanoma cells. In addition, due to the lower anti-oxidant defenses in men, ROS produced by melanoma cells cause more damage to healthy tissues surrounding the tumor, further stimulating metastasis. Therefore, ROS may explain the observed differences between males and females in melanoma survival.     

Interactive Effects of Elevated CO2 and Ozone on Leaf Thermotolerance in Field-grown Glycine max

Humans are increasing atmospheric CO2, ground-level ozone (O3), and mean and acute high temperatures. Laboratory studies show that elevated CO2 can increase thermotolerance of photosynthesis in C3 plants. O3-related oxidative stress may offset benefits of elevated CO2 during heat-waves. We determined effects of elevated CO2 and O3 on leaf thermotolerance of field-grown Glycine max (soybean, C3). Photosynthetic electron transport (φet) was measured in attached leaves heated in situ and detached leaves heated under ambient CO2 and O3. Heating decreased φet, which O3 exacerbated. Elevated CO2 prevented O3-related decreases during heating, but only increased φet under ambient O3 in the field. Heating decreased chlorophyll and carotenoids, especially under elevated CO2. Neither CO2 nor O3 affected heat-shock proteins. Heating increased catalase (except in high O3) and CulZn-superoxide dismutase (SOD), but not MnSOD; CO2 and O3 decreased catalase but neither SOD. Soluble carbohydrates were unaffected by heating, but increased in elevated CO2. Thus, protection of photosynthesis during heat stress by elevated CO2 occurs in field-grown soybean under ambient O3, as in the lab, and high CO2 limits heat damage under elevated O3, but this protection is likely from decreased photorespiration and stomatal conductance rather than production of heat-stress adaptations.     

Interpretation of mushroom as a common therapeutic agent for Alzheimer’s disease and cardiovascular diseases

Alzheimer’s disease (AD) and cardiovascular diseases (CVD) share common etiology and preventive strategies. As the population of old-aged people is increasing worldwide, AD complications tend to afflict global healthcare budget and economy heavily. CVD is the prime cause of global mortality and remains a grave threat to both the developed and the developing nations. Mushroom bio-components may be promising in controlling both diseases. Based mainly on in vitro, ex vivo, cell line and animal studies, this review interprets the polypharmaceutic role of mushrooms treating AD and CVD.     

Structure-activity relationship of polyphenols on inhibition of chemical mediator release from rat peritoneal exudate cells

Summary The effect of phenolic compounds in foodstuffs on histamine and leukotriene B₄ (LTB₄) release from rat peritoneal exudate cells and their antioxidative activity were examined to assess their antiallergenic activities. Among them, triphenols such as pyrogallol and gallic acid inhibited histamine release from the cells, but diphenols did not. On the other hand, o- and p-diphenols such as catechol and hydroquinone with strong antioxidative activity inhibited LTB₄ release as strongly as pyrogallol, but an m-derivative resorcinol with weak antioxidative activity did not. Though carboxylated compounds and their noncarboxylated counterparts were antioxidative, the former exerted a much weaker inhibitory effect on the LTB₄ release than the latter. In flavonols, only myricetin with a triphenolic B ring strongly inhibited histamine release, but all flavonols strongly suppressed LTB₄ release irrespective of the number of OH groups in the B ring. Among flavonoids with an o-diphenolic B ring, flavonol and flavone with a C₄-carbonyl group strongly inhibited LTB₄ release, whereas the activity of anthocyan without C₄-carbonyl was much weaker than the above compounds. These results suggest that triphenolic structure is essential for the inhibition of histamine release. On the other hand, antioxidative activity and membrane permeability of phenolic compounds seemed to be essential for the inhibition of LTB₄ release. In addition, the C₄-carbonyl group seemed to be important for strongly inhibiting LTB₄ release.     

Beneficial effect of vitamin E on the metabolic parameters of diabetic rats

The role of vitamin E in the pathogenesis of diabetes mellitus is unknown. The purpose of this study was to examine the effect of oral administration of vitamin E on some of the metabolic parameters of experimental diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight at 12 weeks of age). Vitamin E (0.2, 0.4, 0.8 mg/kg body weight) was administered orally for a period of 3 weeks to normal and diabetic Wistar rats. In some experiments, Vitamin E was given either before or after the induction of diabetes mellitus. Blood glucose level and weight were recorded for each rat in different groups on a weekly basis. Oral glucose tolerance test (OGTT) was performed on fasted normal, diabetic and vitamin E treated rats at the end of the experiment. Vitamin E significantly (p < 0.01) reduced blood glucose levels in experimental diabetes mellitus at all doses as compared to untreated rats. Vitamin E induced weight loss in normal as well as in diabetic rats. The beneficial effect of vitamin E on the hyperglycaemia of diabetic rats was dose-dependent. Moreover, vitamin E also improved OGTT in diabetic rats compared to untreated diabetics. In conclusion, vitamin E may play a role in glucose metabolism and thus be a useful adjuvant therapy in type I diabetes. (Mol Cell Biochem 261: 35–42, 2004)     

Oxidative stress and activation of proteasome protease during serum deprivation-induced apoptosis in rat hepatoma cells; inhibition of cell death by melatonin

Growth factor deprivation-induced apoptosis has been shown in various cell systems and is recognized as one of the standard models for the study of programmed cell death. The mechanism of induction of apoptosis by serum deprivation is still not clear. The objective of the present study was to investigate if serum-deprivation causes oxidative stress, which then leads to apoptotic death. We have demonstrated that indeed, there was a significant increase in reactive oxygen species following serum deprivation of 5123tc hepatoma cells. Furthermore, treatment with anti-oxidants; melatonin or vitamin E, prevented cell death caused by serum-deprivation. We also demonstrated that there was activation of proteasome proteases and decrease in glutathione levels following serum deprivation. Interestingly, melatonin treatment blocked these changes and rescued the cells from apoptosis induced by serum-deprivation. These results indicated that oxidative stress may play a causal role in the induction of apoptosis induced by serum deprivation.     

Atrial fibrillation in β-thalassemia patients with a focus on the role of iron-overload and oxidative stress: A review

Cardiac complications including arrhythmia and especially atrial fibrillation (AF) are common causes of death in β-thalassemia patients. The main factor in the etiopathogenesis of these complications is iron overload, which results in increased oxidative stress. Although there is a known association between cardiac complications and iron overload in β-thalassemia patients, there is no comprehensive review on AF and excessive iron with a focus on oxidative stress in these patients. The aim of this article was to review the different aspects of AF in β-thalassemia patients with a focus on the prevention and treatment of AF by using iron chelators and/or anti-oxidants. AF in β-thalassemia patients is more common than in the general population. One of the most important causes of AF is cardiac iron overload and the harmful effects of increased oxidative stress. Iron-induced AF can be reversed by using an intensive iron chelation regimen. Based on a few experimental studies, the combination of iron chelators with some anti-oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. However, the effect of such combinations on cardiac arrhythmias should be further evaluated with animal and human studies.