The reactivity of catecholamine neurotransmitters and the related metabolites were precisely investigated toward 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and reactive oxygen species. Catecholamines reacted immediately with DPPH radicals, their reactivity being stronger than that of ascorbic acid as a reference. Superoxide scavenging activities of catecholamines determined by WST-1 and electron spin resonance (ESR) spin trapping methods were also high. Whereas tyrosine, the dopamine precursor showed no reactivity toward superoxide. The reactivity toward singlet oxygen was evaluated by observing specific photon emission from singlet oxygen. The results revealed that reactivity of catecholamines was markedly higher than that of sodium azide, and catechin as catechol reference. The reaction of catecholamines and singlet oxygen was further studied by ESR using 55-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping reagent and rose bengal as photosensitizer. DMPO-OH signal of epinephrine was significantly small compared to other catecholamines, catechin, and 4-methylcatechol as a reference compound and was as small as that of tyrosine. The signal formation was totally dependent on singlet oxygen, and the presence of catechol compounds. These results indicated that epinephrine is the most potent singlet oxygen quencher than other catecholamines, and the secondary amino group in its alkyl side chain could play a role in unique singlet oxygen quenching property of epinephrine.
Preeclampsia (PE) is a major contributor to maternal and fetal mortality. The cause of preeclampsia remains unclear, but oxidative stress on the endothelium leading to endothelial dysfunction is said to be the root cause of the disease. The aim of this study was to measure and determine the plasma levels of key angiogenic factors in pregnancy as an indicator for the early onset of preeclampsia in pregnancy. Plasma levels of circulating a soluble fms like tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor, vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), both pro-angiogenic factors were analyzed in normal pregnant Malaysian women (control group, n = 34), women with pregnant induced hypertension (PIH, n = 34) and women with preeclampsia (PE, n = 34) all at three gestational ages, 24–28 weeks (early pregnancy: EP), 32–36 weeks (late pregnancy: LP) and 6 weeks after delivery (postpartum: PN). The plasma levels of angiogenic factors were determined by ELISA. sFlt-1 levels were elevated in PIH and PE patients as compared to controls. PIGF and VEGF were significantly decreased in PIH and PE as compared to the controls. These results suggest that elevated concentration of sFlt-1 and suppressed levels of PIGF and VEGF may contribute to the development of hypertension in pregnancy which precedes preeclampsia.
It is beneficial to seek scientific basis for the effects of functional foods. Natural pigments derived from plants are widely known as possible antioxidants. Black soybean contains a larger amount of anthocyanins than regular soybean. Here we studied the antioxidative effect of a beverage obtained via citric acid fermentation of black soybean (BBS), using a rat model of renal oxidative injury induced by a renal carcinogen, ferric nitrilotriacetate. BBS (10 ml/kg) was orally administered 30 min before ferric nitrilotriacetate treatment. Renal lipid peroxidation was significantly suppressed in the BBS-pretreated animals concomitant with decrease in 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Maintenance of renal activities of antioxidative enzymes including catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, glucose-6-phosphate dehydrogenase and quinone reductase was significantly better in the BBS-pretreated rats. Elevation of serum creatinine and urea nitrogen was significantly suppressed in the BBS-pretreated rats. These data suggest that dietary intake of BBS is useful for the prevention of renal tubular oxidative damage mediate by iron, and warrant further investigation.
The bifidogenic effect of an infant formula supplemented with inulin and fructooligosaccharides (4.0 g/l) was examined clinically and in vitro, and compared that of mature breast milk. In a 28-day clinical study, fecal samples of 21 infants, divided into two groups: one receiving the infant formula and the other breast milk, were microbiologically and biochemically examined. In the in vitro investigation, microbiological and biochemical changes in the infant formula and breast milk induced by the action of bifidobacteria isolated from infant feces were examined. There were no significant differences in the fecal numbers of lactobacilli, total aerobes, anaerobes or yeasts and fungi. In contrast, the bifidobacteria numbers in the stools increased significantly during the study in the infants receiving the supplemented formula. The comparative in vitro test showed that the bifidogenic effect was similar for infant formula and breast milk in terms of the number of bifidobacteria. Consumption of infant formula with added inulin and fructooligosaccharides stimulated the bifidogenic effect, both clinically and in vitro. The in vitro test can quickly and objectively determine the bifidogenic effect of infant formula and indicate their quality. However, a clinical test is necessary to determine the acceptance and biological value of infant formula.
Inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia (FD). However, detailed data regarding the possible association between the genetic factors of inflammation related molecules and FD are not available. Toll like receptor 2 (TLR2) and mannan-binding lectin (MBL) protein play important roles in the innate immune activation. We aimed to clarify the association between common polymorphisms of TLR2 and MBL2 genes with FD in Japanese subjects. TLR2 −196 to −174 del and MBL2 codon54 G/A polymorphisms were genotyped in 111 FD patients according to Rome III criteria and 106 asymptomatic controls. Non-significant correlation was found between TLR2 and MBL2 polymorphisms with FD. However, in Helicobacter pylori (H. pylori) positives, we found significant inverse association between TLR2 −196 to −174 del carrier and FD among H. pylori positive subjects (Adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.23–0.996, p = 0.0488). We also found significant inverse association between the same genotype with postprandial distress syndrome (PDS) among H. pylori positive subjects (Adjusted OR = 0.22, 95% CI = 0.07–0.69, p = 0.0099). Our data suggest that TLR2 −196 to −174 del carriers’s status but not MBL2 codon54 G/A is inversely related to the risk with FD in H. pylori-infected subjects.
The present study attempted to clarify whether over-secretion of glucocorticoids in the serum caused by increased hypothalamus-pituitary-adrenal activity induces oxidative stress in the rat brain, and how the stress causes the emergence of cognitive deficits. When rats were subcutaneously injected with corticosterone, lipid hydroperoxides and protein carbonyls increased markedly in the hippocampus in association with a decrease in activity of antioxidative enzymes, such as superoxide dismutase, catalase and glutathione peroxidase. These results suggest that high-level corticosterone in the serum induces reactive oxygen species (ROS), leading to oxidative damage in the hippocampus. After administration of corticosterone to rats, glucose and superoxide levels in the serum increased markedly. Furthermore, pyramidal cell apoptosis was observed to accompany the loss of glucocorticoid receptors at the cornus ammonis 1 region of the hippocampus. Rats injected with corticosterone showed marked deficits in memory function. The present results imply that ROS generated from the glycation reaction of increased glucose levels caused by gluconeogenesis activation through glucocorticoid with proteins in the serum attack the hippocampus to induce neurodegeneration, resulting in cognitive deficits in rats.
The relationship between the levels of two different crosslink compounds, pentosidine and pyridinoline, in human diabetic cataract lenses was investigated to elucidate the pathogenic mechanism of diabetic cataract. Subjects were classified into diabetes mellitus (DM) group and non-DM group according to the presence or absence of DM. The levels of the crosslink compounds were determined using high-performance liquid chromatography and spectrofluorometry after acid hydrolysis. In the non-DM group the pentosidine level was significantly and positively correlated with the pyridinoline level and age. In the DM group the pentosidine level was not significantly correlated with either pyridinoline level or age. Pyridinoline levels and age were not significantly correlated in either group. The increase in crosslink compounds due to glycation and the relationship between the compounds are changed in DM lenses.
Dexrazoxane (ICRF-187) has been clinically used to reduce doxorubicin-induced cardiotoxicity for more than 20 years. It has been proposed that dexrazoxane may act through its rings-opened hydrolysis product ADR-925, which can either remove iron from the iron-doxorubicin complex or bind to free iron, thus preventing iron-based oxygen radical formation. However, it is not known whether the antioxidant actions of dexrazoxane are totally dependent on its metabolization to its rings-opened hydrolysis product and whether dexrazoxane has any effect on the iron-independent oxygen free radical production. In this study, we examined the scavenging effect of dexrazoxane on hydroxyl, superoxide, lipid, DPPH and ABTS+ free radicals in vitro solution systems. The results demonstrated that dexrazoxane was an antioxidant that could effectively scavenge these free radicals and the scavenging effects of dexrazoxane did not require the enzymatic hydrolysis. In addition, dexrazoxane was capable to inhibit the generation superoxide and hydroxyl radicals in iron free reaction system, indicating that the antioxidant properties of dexrazoxane were not solely dependent on iron chelation. Thus the application of dexrazoxane should not be limited to doxorubicin-induced cardiotoxicity. Instead, as an effective antioxidant that has been clinically proven safe, dexrazoxane may be used in a broader spectrum of diseases that are known to be benefited by antioxidant treatments.
Soybean-derived phosphatidylserine (Soy-PS) is a phosphatidylserine made from soybean lecithin by enzymatic reaction with L-serine. A double-blind, randomized controlled study was conducted to investigate the effects of Soy-PS on the cognitive functions of the elderly Japanese subjects with memory complaints. Seventy-eight elderly people with mild cognitive impairment (50–69 years old) were randomly allocated to take Soy-PS (100 mg, 300 mg/day) or placebo for 6 months. As a result, there was no difference in blood markers and vital signs during Soy-PS treatment and any side effect caused by Soy-PS treatment was not observed. Neuropsychological test scores were similarly increased in all groups including placebo group. However, in the subjects with relatively low score at baseline, the memory scores in PS treated groups were significantly increased against the baseline, while those of placebo group remained unchanged. And the memory improvements in Soy-PS-treated groups were mostly attributed to the increase in delayed verbal recall, a memory ability attenuated in the earliest stage of dementia. In conclusion, Soy-PS used in this study is considered as safety food ingredient and 6 months of Soy-PS supplementation could improve the memory functions of the elderly with memory complaints.
Non-steroidal anti-inflammatory drug (NSAID)-related small intestinal complications exist, since developed new diagnostic modalities, such as balloon and capsule endoscopies. Some experiments have shown rebamipide to protect from NSAID-induced small intestinal complications. The purpose of this study is to investigate whether the effective concentrations of rebamipide (COR) are present in the small intestine after taking an ordinary clinical dose and double dose of this drug. Twelve healthy male subjects were enrolled. After taking 100 or 200 mg of rebamipide, balloon enteroscopy was performed at 1 and 3 h, and biopsy samples were obtained from the jejunum and the stomach. Venous blood samples were taken simultaneously. Samples were analyzed by high-performance liquid chromatography. The mean COR in the jejunum was higher than 100 μM at 1 h and higher than 10 μM at 3 h in both the 100 and 200 mg groups. Mean COR in the stomach was less than 100 μM at 1 h in the 100 mg group; however it was higher than 100 μM in the 200 mg group. In conclusion, the COR level in the jejunum was sufficient to protect for NSAID-induced gastrointestinal complications.
The obese patients with diabetes or cardiovascular risk factors are associated with increased risk of colorectal cancer as well as adenomas under the shared pathogenesis related to atherosclerosis. Here we determined the association between increased arterial stiffness and colorectal adenomas incorporating parameters including age, gender, waist circumference, body mass index, lipid profiles, fasting glucose, and blood pressure. Subjects who simultaneously underwent colonoscopies and pulse wave velocity (PWV) determinations between July 2005 and September 2006 were analyzed, based on which the subjects were classified into two groups as patients group with colorectal adenomas (n = 49) and control group (n = 200) with normal, non-polypoid benign lesions or hyperplastic polyps. Uni- and multi-variate analyses were performed to calculate the odd ratio for colon adenomas. Based on uni-variate analysis, age, waist circumference, body mass index, heart-femoral PWV (hfPWV), and brachial-ankle PWV were significantly associated with adenomas (p<0.05) and multiple logistic regression analysis showed that the heart-femoral PWV, waist circumference, and the levels of LDL-C were significant risk factor for colorectal adenoma. However, arterial stiffness did not affect the progression of colon adenoma. The finding that hfPWV, reflecting aortic stiffness, was increased in patients with colorectal adenomas lead to conclusion that patients who have prominently increased arterial stiffness can be recommended to undergo colonoscopic examinations and at the same time we also recommend counseling about the risk for atherosclerosis in those who have colorectal adenomas.
The article published in J. Clin. Biochem. Nutr. 2007, 41(2), 132–138 was withdrawn by the Editors on August 9, 2010, because it was not original work and constituted a breach of journal’s ethical policy