Reactive oxygen species play a central role in the pathophysiology of the age-related decrease in male fertility. It has been reported that the total protein of DJ-1 was decreased in a proteomic analysis of seminal plasma from asthenozoospermia patients and a DJ-1 protein acts as a sensor of cellular redox homeostasis. Therefore, we evaluated the age-related changes in the ratio of the oxidized/reduced forms of the DJ-1 protein in the epididymis. In addition, the protective effects of S-allyl cysteine (SAC), a potent antioxidant, were evaluated against sperm dysfunction. Male rats aged 15–75 weeks were used to assess age-associated sperm function and oxidative stress. Sperm count increased until 25 weeks, but then decreased at 50 and 75 weeks. The rate of sperm movement at 75 weeks was decreased to approximately 60% of the rate observed at 25 weeks. Expression of DJ-1 decreased, but oxidized-DJ-1 increased with age. In addition, 4-hydroxy-2-nonenal modified proteins in the epididymis increased until 50 weeks of age. The total number and DNA synthetic potential of the sperm increased until 25 weeks, and then decreased. In rats 75 weeks of age, SAC (0.45% diet) attenuated the decrease in the number, motility, and DNA synthesis of sperm and inhibited the oxidized proteins. These results suggest that SAC ameliorates the quality of sperm subjected to age-associated oxidative stress.
Prostaglandin E2 plays a role in an array of pathophysiological responses, including inflammation, carcinogenesis and so on. Prostaglandin E2 is synthesized from arachidonic acid by the enzymes cyclooxygenase and prostaglandin E synthase. In some pathological conditions, the isozymes cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are transiently induced, leading to prostaglandin E2 overproduction. The present study showed that Dioscorea japonica extract suppresses mRNA expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in human non-small-cell lung carcinoma A549 cells in a dose-dependent manner. The suppressive effects of Dioscorea japonica extract on the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 were confirmed by Western blotting, cyclooxygenase activity and prostaglandin E2 production. Dioscorea japonica extract induced the translocation of nuclear factor-κB from the nucleus to the cytosol and inhibited the activity of the cyclooxygenase-2 promoter. Furthermore Dioscorea japonica extract suppressed the expression of the anti-apoptotic factor B-cell chronic lymphocytic leukemia/lymphoma 2 and enhanced apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive intensity in A549 cells. These results suggest that Dioscorea japonica extract suppresses the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1, with the regulation of the transcriptional activity of cyclooxygenase-2, and induces apoptosis in cancer cells. Thus, Dioscorea japonica may contribute to the prevention of prostaglandin E2-mediated pathophysiological responses such as carcinogenesis and inflammation.
Dry mouth, which is characterized by decreased salivation, has a number of causes; the involvement of estrogen has been suggested as symptoms typically develop in middle-aged females. However, there is a lack of consensus regarding the treatment of this condition. Soy isoflavones, a subgroup of flavonoids, are abundantly found in the soy germ. They are thought to exert a number of effects by specifically binding to estrogen receptors due to their structural similarity to estrogen. Recently, soy isoflavones have been found to exert antioxidant effects, ameliorating disorders caused by reactive oxygen/free radicals. Based on these observations, the effects of soybean isoflavones on impaired salivary secretion were studied in patients with dry mouth. Soy isoflavone aglycones were administered at 25 mg per day to 15 subjects with an average age of 67.9 ± 8.0 years for 2 months, and salivary secretion was analyzed. The results showed a significant improvement based on the saliva flow rate and self-completed questionnaire, thus suggesting the usefulness of isoflavones in improving the symptoms of salivary gland hypofunction.
Post-operative chylothorax can be cured by a medium-chain triglyceride (MCT)-rich diet. However, there is concern that an MCT-rich diet results in clinical and biochemical deficiencies in fat-soluble vitamins and fatty acids. We compared fat-soluble vitamins status and fatty acids status before and after administration of an MCT-rich diet. Nine children with congenital heart disease developed chylothorax after cardiac surgery. Blood samples were drawn from each subject twice, first prior to administration of an MCT-rich diet and secondly when the chylothorax was clinically cured and the MCT diet discontinued. Both blood samples were analyzed for retinol and 25-hydroxy vitamin D concentrations, the ratio of α-tocopherol to total lipids (α-TE/TL), coagulogram, and the fatty acid composition in plasma and erythrocyte membrane phospholipids. In spite of a decrease in the α-TE/TL ratio (3.78 ± 0.89 vs 2.36 ± 0.44 mg/g, p<0.05), this decrease did not reach the deficiency cut-off level. Linoleic acid in both plasma and erythrocyte membrane lipids decreased significantly (25.25 ± 8.06 vs 14.25 ± 2.88%, and 11.19 ± 2.15 vs 6.89 ± 2.45%, respectively). Administration of an MCT-rich diet for treatment of postoperative chylothorax caused a reduction in vitamin E status and linoleic acid, but without any symptoms of deficiency.
Comparisons between the acid inhibitory effects of rabeprazole and esomeprazole after single oral administration with standard doses have not been previously presented. We examined intra-gastric pH after oral administrations of these two proton pump inhibitors using 24-h pH monitoring. Fifty-four normal volunteers not infected by Helicobacter pylori were investigated. Using a cross-over design, we administered 10 mg of rabeprazole or 20 mg of esomeprazole in 27 at 30 min after supper and in the remaining 27 subjects at 15 min before supper, and performed 24-h pH monitoring. Intra-gastric pH data were nearly identical when the proton pump inhibitors were taken after meals. Even if the data were compared in different CYP2C19 genotypes, rabeprazole and esomeprazole did not show the difference. In poor metabolizer, both of the drugs showed stronger acid inhibition. When taken before meals, intra-gastric pH after esomeprazole administration was slightly but not significantly higher than that observed after rabeprazole administration not only in daytime but also in nighttime period. In conclusion, rabeprazole and esomeprazole were similarly effective when administered after a meal.
The anti-nephrolithiasis effect of Xue Niao An (XNA) capsules is explored by analyzing urine metabolic profiles in mouse models, with ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). An animal model of calcium oxalate crystal renal deposition was established in mice by intra-abdominal injection of glyoxylate. Then, treatment with XNA by intra-gastric administration was performed. At the end of the study, calcium deposition in kidney was measured by Von Kossa staining under light microscopy, and the Von Kossa staining changes showed that XNA significantly alleviated the calcium oxalate crystal deposition. Meanwhile, urine samples for fifteen metabolites, including amino acids and fatty acids, with significant differences were detected in the calcium oxalate group, while XNA treatment attenuated metabolic imbalances. Our study indicated that the metabonomic strategy provided comprehensive insight on the metabolic response to XNA treatment of rodent renal calcium oxalate deposition.
Lack of exercise and excessive food intake are known to be the important causes of nonalcoholic steatohepatitis (NASH). To elucidate the relationship between lifestyle and NASH, we surveyed exercise and dietary habits, comparing them among 171 biopsy-proven NASH patients, 29 nonalcoholic fatty liver (NAFL) patients and 49 normal subjects. Dietary habits including the duration of dinner time, amount of rice at dinner, and weekly frequencies of meat, fries, Chinese noodles, sweets, and instant food consumption were significantly different in male NASH patients compared to normal male subjects. In women, differences were seen in the amount of rice at dinner, frequency of eating out, and proclivity for sweets. In male NASH patients, the frequency of physical exercise was significantly lower. The lifestyle tendencies of NASH were almost similar to those of NAFL. In the comparison between obese NASH and non-obese NASH, no clear lifestyle differences were found. In conclusion, the most striking result of this survey was that the lifestyle of males contributed significantly to the development of NASH. These results point to treatment of NASH in males. In female NASH patients, lifestyle differences were minimal, and the effects of other factors such as genetic background will need to be investigated.
An increase in the proportion of fatty acids with higher numbers of double bonds is believed to increase lipid peroxidation, which augments the risk for many chronic diseases. (n-3) Polyunsaturated fatty acids provide various health benefits, but there is a concern that they might increase lipid peroxidation. We examined the effects of docosahexaenoic acid [22:6 (n-3)] supplementation on lipid peroxidation markers in plasma and red blood cells (RBC) and their associations with red blood cell and plasma fatty acids. Hypertriglyceridemic men (n = 17 per group) aged 39–66 years participated in a double-blind, randomized, placebo-controlled, parallel study. They received no supplements for the first 8 days and then received 7.5 g/day docosahexaenoic acid oil (3 g/day docosahexaenoic acid) or olive oil (placebo) for 90 days. Fasting blood samples were collected 0, 45, and 91 days after supplementation. Docosahexaenoic acid supplementation did not change plasma or RBC concentrations of lipid peroxidation markers (total hydroxyoctadecadienoic acid, total hydroxyeicosatetraenoic acid, total 8-isoprostaglandin F2α, 7α-hydroxycholesterol, 7β-hydroxycholesterol) when pre- and post-supplement values were compared. However, the post-supplement docosahexaenoic acid (DHA) concentration was inversely associated with RBC concentrations of ZE-HODE, EE-HODE, t-HODE, and total 8-isoprostaglandin F2α, (p<0.05). RBC concentration of hydroxycholesterol was also inversely associated with DHA but it did not attain significance (p = 0.07). Our results suggest that increased concentration of DHA in RBC lipids reduced lipid peroxidation. This may be another health benefit of DHA in addition to its many other health promoting effects.
Thalassemia patients are at high risk of iron-induced toxicity and oxidative stress consequences. The present cross-sectional study is conducted to determine whether or not lipid peroxidation or protein oxidation is correlated with iron parameters in patients with thalassemia major. To prove this hypothesis, malondialdehyde and total carbonyl were correlated with the degree of excess iron concentration in the patients. A total of 118 Arabic Iraqi patients and 30 healthy children were participated in the present study. Results showed a significant increase (p<0.05) in serum total carbonyls, malondialdehyde and the iron indices of patients as compared with the control group. Total iron binding capacity and transferrin concentrations decreased significantly (p<0.05) in patients with thalassemia compared with the control group. The results also showed a lack of a significant correlation between each serum malondialdehyde and total carbonyl with each component of iron status. In conclusion, total carbonyls and malondialdehyde were increased in thalassemia patients indicating the vulnerability of these patients to tissue injury caused by oxidative stress. The formation of total carbonyl and malondialdehyde are independent of excess non-labile iron concentration, indicating that different mechanisms are involved in injury caused by the labile iron and in the formation of oxidation end products.
Thermal plasmas and lasers are used in medicine to cut and ablate tissues and for coagulation. Non-equilibrium atmospheric pressure plasma (NEAPP) is a recently developed, non-thermal technique with possible biomedical applications. Although NEAPP reportedly generates reactive oxygen/nitrogen species, electrons, positive ions, and ultraviolet radiation, little research has been done into the use of this technique for conventional free radical biology. Recently, we developed a NEAPP device with high electron density. Electron spin resonance spin-trapping revealed •OH as a major product. To obtain evidence of NEAPP-induced oxidative modifications in biomolecules and standardize them, we evaluated lipid peroxidation and DNA modifications in various in vitro and ex vivo experiments. Conjugated dienes increased after exposure to linoleic and α-linolenic acids. An increase in 2-thiobarbituric acid-reactive substances was also observed after exposure to phosphatidylcholine, liposomes or liver homogenate. Direct exposure to rat liver in saline produced immunohistochemical evidence of 4-hydroxy-2-nonenal- and acrolein-modified proteins. Exposure to plasmid DNA induced dose-dependent single/double strand breaks and increased the amounts of 8-hydroxy-2'-deoxyguanosine and cyclobutane pyrimidine dimers. These results indicate that oxidative biomolecular damage by NEAPP is dose-dependent and thus can be controlled in a site-specific manner. Simultaneous oxidative and UV-specific DNA damage may be useful in cancer treatment.
Tsumura Suzuki Obese Diabetes (TSOD) mouse, a model of obese type 2 diabetes, older than around 11 weeks of age develops diabetic phenotypes. Previous studies have indicated that the development of diabetes is partly due to three loci associated with body weight and glucose homeostasis. However, little is known about the initial events triggering the development of the diabetic phenotypes in TSOD mouse. Here, we investigated the alteration of diabetes-related parameters, including the levels of blood glucose and inflammatory cytokines, and the oxidative stress status, in young TSOD mice. TSOD mice at 5 weeks of age showed increases in body weight and plasma total cholesterol level, but not hyperglycemia or impaired glucose tolerance, compared with age-matched control Tsumura Suzuki Non-Obese (TSNO) mice. Plasma tumor necrosis factor (TNF)-α and interleukin (IL)-6 were not detected in TSOD mice at 5 weeks of age. However, plasma total hydroxyoctadecadienoic acid (tHODE), a biomarker of oxidative stress, was increased in TSOD mice relative to TSNO mice at same age. The results demonstrated that young TSOD mice are exposed to oxidative stress before developing the diabetic phenotypes, and suggested that oxidative stress is an initial event triggering the development of diabetes in TSOD mice.
Carnitine is a vitamin-like compound that plays important roles in fatty acid β-oxidation and the control of the mitochondrial coenzyme A/acetyl-CoA ratio. However, carnitine is not added to ordinary enteral nutrition or total parenteral nutrition. In this study, we determined the serum carnitine concentrations in subjects receiving ordinary enteral nutrition (EN) or total parenteral nutrition (TPN) and in patients with inflammatory bowel diseases to compare its levels with those of other nutritional markers. Serum samples obtained from 11 EN and 11 TPN patients and 82 healthy controls were examined. In addition, 10 Crohn’s disease and 10 ulcerative colitis patients with malnutrition who were barely able to ingest an ordinary diet were also evaluated. Carnitine and its derivatives were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The carnitine concentrations in EN and TPN subjects were significantly lower compared with those of the control subjects. Neither the serum albumin nor the total cholesterol level was correlated with the carnitine concentration, although a significant positive correlation was found between the serum albumin and total cholesterol levels. Indeed, patients with CD and UC showed significantly reduced serum albumin and/or total cholesterol levels, but their carnitine concentrations remained normal. In conclusion, only a complete blockade of an ordinary diet, such as EN or TPN, caused a reduction in the serum carnitine concentration. Serum carnitine may be an independent biomarker of malnutrition, and its supplementation is needed in EN and TPN subjects even if their serum albumin and total cholesterol levels are normal.
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