Oxidative Stress Induced by Chemotherapy: Evaluation of Glutathione and Its Related Antioxidant Enzyme Dynamics in Patients with Colorectal Cancer.

One of the mechanisms of chemotherapy is to increase the oxidative stress of cancer cells, leading to their apoptosis. Glutathione (GSH) and its related antioxidant enzymes might be stimulated to cope with increased oxidative stress during chemotherapy. Here, we studied the fluctuation in oxidative stress and GSH-related antioxidant capacities before tumor resection, after tumor resection, and after resection either with or without chemotherapy in patients with colorectal cancer (CRC). This was a cross-sectional and follow-up design. We followed patients before having tumor resection (pre-resection), one month after tumor resection (post-resection), and after the first scheduled chemotherapy (post-chemo). If patients were required to receive chemotherapy after tumor resection, they were assigned to the chemotherapy group. Eligible patients were scheduled to undergo six to twelve cycles of chemotherapy at 2-week intervals and received single, double, or triple chemotherapeutic drugs as required. Those patients who did not require chemotherapy were assigned to the non-chemotherapy group. Indicators of oxidative stress and GSH-related antioxidant capacities were determined at the above three time points. We found in 48 patients of the chemotherapy group and in 43 patients of the non-chemotherapy group different fluctuations in levels of oxidative stress indicators and GSH-related antioxidant capacities starting from pre-resection, post-resection through the post-chemo period. Both groups showed significantly or slightly increased levels of advanced oxidation protein products (AOPP), GSH, and its related enzymes in tumor tissues compared to adjacent normal tissues. Patients in the chemotherapy group had significantly lower plasma levels of GSH and glutathione disulfide (GSSG), but had significantly higher plasma glutathione peroxidase and glutathione reductase activities than patients in the non-chemotherapy group post-chemo. Plasma levels of malondialdehyde and AOPP were positively or negatively associated with GSH and GSSG levels post-chemo after adjustment for age, sex, and histological grading in patients receiving chemotherapy. These significant associations were, however, not seen in patients without chemotherapy. Patients with CRC may require higher GSH demands to cope with a greater oxidative stress resulting from chemotherapy.

Trace Elements Status and Their Associations With Related Antioxidant Enzyme Activities in Patients Receiving Peritoneal Dialysis and Hemodialysis.

OBJECTIVE: It remains ambiguous as to whether the status of trace elements would affect their related enzyme activities toward defending a possible higher oxidative stress in patients receiving peritoneal dialysis (PD) or hemodialysis (HD) treatment. We investigated copper (Cu), zinc (Zn), and selenium (Se) status in patients receiving PD or HD treatments and further determined the association of these trace elements with their related antioxidant capacities in those patients. METHODS: Sixty PD and 80 HD patients before and after HD treatment had their blood drawn. Demographic, clinical, and 24-hour diet recall data were recorded and collected. Plasma trace elements, oxidative stress indicators, and antioxidant enzyme activities were measured. RESULTS: Patients receiving PD or HD treatments experienced similar Zn and Cu intakes. PD and HD patients displayed adequate mean plasma Cu, Zn, and Se levels. Patients receiving PD treatment showed significantly higher levels of Cu, Zn, advanced oxidation protein products (AOPPs), and superoxide dismutase (SOD) activity, but had significantly lower levels of Se and total antioxidant capacity when compared to levels in the HD patients at the pre-HD session. The levels of 3 trace elements and AOPP increased significantly, while the levels of glutathione (GSH), oxidized glutathione (GSSG), GPx, and SOD activities decreased significantly after receiving HD treatment than did the levels in the pre-HD session. Plasma Cu, Se, and Zn levels had a different correlation with plasma AOPP level, GPx, and SOD activities during PD, pre- or post-HD sessions. Plasma Cu, Zn, and Se levels did not have any association with their associated enzyme activities in patients with PD, while plasma Cu and Zn levels may have influenced SOD activity in HD patients. CONCLUSIONS: An adequate Cu, Zn, and Se status is required in order to help their associated enzyme activity cope with increased oxidative stress during PD or HD sessions.

Mei-Gin Formula Ameliorates Obesity through Lipolysis, Fatty Oxidation, and Thermogenesis in High-Fat Diet-Induced Obese Rats.

Obesity is a metabolic dysfunction characterized by excessive body fat deposition as a consequence of an energy imbalance. Novel therapeutic strategies have emerged that are safe and have comparatively low side effects for obesity treatment. Functional foods and nutraceuticals have recently received a great deal of attention because of their components with the properties of antimetabolic syndrome. Based on our previous in vitro and in vivo investigations on anti-adipogenesis activity and improved body fat accumulation in serials, the combination of three ingredients (including bainiku-ekisu, black garlic, and Mesona procumbens Hemsl), comprising the Mei-Gin formula (MGF), was eventually selected as a novel inhibitor that exhibited preventive effects against obesity. Herein, we verify the anti-obesity effects of MGF in obese rats induced by a high-fat diet and discuss the potential molecular mechanisms underlying obesity development. Oral administration of MGF significantly suppressed the final body weight, weight change, energy and water intake, subcutaneous and visceral fat mass, liver weight, hepatic total lipids and triglycerides (TG), and serum levels of TG, triglycerides (TC), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (AST), uric acid, and ketone bodies and augmented fecal total lipids, TG, and cholesterol excretion in the high-dose MGF-supplemented groups. Furthermore, the corresponding lipid metabolic pathways revealed that MGF supplementation effectively increased lipolysis and fatty acid oxidation gene expression and attenuated fatty acid synthesis gene expression in the white adipose tissue (WAT) and liver and it also increased mitochondrial activation and thermogenic gene expression in the brown adipose tissue (BAT) of rats with obesity induced by a high-fat diet (HFD). These results demonstrate that the intake of MGF can be beneficial for the suppression of HFD-induced obesity in rats through the lipolysis, fatty oxidation, and thermogenesis pathway. In conclusion, these results demonstrate the anti-obesity efficacy of MGF in vivo and suggest that MGF may act as a potential therapeutic agent against obesity.

An Innovative Mei-Gin Formula Exerts Anti-Adipogenic and Anti-Obesity Effects in 3T3-L1 Adipocyte and High-Fat Diet-Induced Obese Rats.

BACKGROUND: To investigate the potential anti-obesity properties of an innovative functional formula (called the Mei-Gin formula: MGF) consisting of bainiku-ekisu, Prunus mume (70% ethanol extract), black garlic (water extract), and Mesona procumbens Hemsl. (40% ethanol extract) for reducing lipid accumulation in 3T3-L1 adipocytes in vitro and obese rats in vivo. MATERIAL AND METHODS: The prevention and regression of high-fat diet (HFD)-induced obesity by the intervention of Japan Mei-Gin, MGF-3 and -7, and positive health supplement powder were investigated in male Wistar rats. The anti-obesity effects of MGF-3 and -7 in rats with HFD-induced obesity were examined by analyzing the role of visceral and subcutaneous adipose tissue in the development of obesity. RESULTS: The results indicated that MGF-1-7 significantly suppressed lipid accumulation and cell differentiation through the down-regulation of GPDH activity, as a key regulator in the synthesis of triglycerides. Additionally, MGF-3 and MGF-7 exhibited a greater inhibitory effect on adipogenesis in 3T3-L1 adipocytes. The high-fat diet increased body weight, liver weight, and total body fat (visceral and subcutaneous fat) in obese rats, while these alterations were effectively improved by the administration of MGF-3 and -7, especially MGF-7. CONCLUSION: This study highlights the role of the Mei-Gin formula, particularly MGF-7, in anti-obesity action, which has the potential to be used as a therapeutic agent for the prevention or treatment of obesity.

Anti-fatigue effects of enzyme-hydrolyzed okara in C2C12 myotubes and Sprague-Dawley rats.

Okara is a by-product of tofu or soymilk production processes. The disposal of huge quantities of okara is a significant issue. Based on previous reports, protein hydrolysis can release excess free amino acids and small peptides from okara and exhibit anti-fatigue function. We aimed to investigate the anti-fatigue effect of okara protein hydrolysate (OPH) in vitro and in vivo. In the first phase, we treated C2C12 myotubes with different processed OPHs to detect mitochondrial functions. The results revealed that OPH hydrolyzed with alcalase containing 2% E/S for 2 h increased the mitochondrial mRNA level (cytochrome b and cytochrome c oxidase I) and enzyme activity (citrate synthase and cytochrome c oxidase) most efficiently. In the second phase, we conducted animal studies to assess the anti-fatigue function of OPH. After acclimatization, 8 week-old male Sprague-Dawley (SD) rats were randomly classified into four groups: (1) control group, (2) 1X-OPH, (3) 2X-OPH, and (4) 5X-OPH (8 rats per group, treated for 28 days). The results indicated that the intake of OPH for 28 days increased the exhaustive swimming time of rats and lowered the increment of the lactate ratio, as well as the activity of lactate dehydrogenase and creatine kinase. These results indicated that OPH improves exercise performance and anti-fatigue function in male SD rats. Therefore, OPH could be a potential health supplement for anti-fatigue function.

Cysteine Regulates Oxidative Stress and Glutathione-Related Antioxidative Capacity before and after Colorectal Tumor Resection.

Cysteine might scavenge free radicals and is a limiting substrate for the cellular synthesis of glutathione (GSH). We investigated the association of cysteine with oxidative stress and GSH-related antioxidant capacity in colorectal cancer (CRC) patients. Plasma samples were drawn from 66 patients 1 day before (pre-resection) and 4 weeks after resection (post-resection). Tumor and adjacent normal tissues were collected. We measured levels of plasma and tissue cysteine, homocysteine, oxidative stress indicators (malondialdehyde, MDA; advanced oxidation protein products, AOPP), GSH, and antioxidant enzyme activities. After tumor resection, patients had significantly higher levels of plasma cysteine, homocysteine, MDA, AOPP, and GSH-related antioxidant enzyme activities when compared with pre-resection. Levels of cysteine, homocysteine, AOPP and all antioxidant capacity indicators in tumor tissue were significantly higher than those levels in the adjacent normal tissue. Plasma cysteine levels measured at pre-resection were positively associated with MDA levels in the tumor and in the adjacent normal tissues. Cysteine levels in tumor and adjacent normal tissues were significantly associated with tissue levels of homocysteine, almost as indicators of oxidative stress and antioxidant capacities. Cysteine in the circulation was likely utilized to mediate GSH-related antioxidant capacity and further cope with increased oxidative stress in tumor and adjacent normal tissues.

Indoxyl sulfate, homocysteine, and antioxidant capacities in patients at different stages of chronic kidney disease.

BACKGROUND/OBJECTIVES: Increased levels of uremic toxins and decreased antioxidant capacity have a significant impact on the progression of chronic kidney disease (CKD). However, it remains unclear whether they interact with each other to mediate the damage of kidney function. The purpose of this study was to investigate whether uremic toxins (i.e., homocysteine and indoxyl sulfate [IS]), as well as glutathione-dependent antioxidant enzyme activities are dependently or independently associated with kidney function during different stages of CKD patients. SUBJECTS/METHODS: One hundred thirty-two patients diagnosed with CKD at stages 1 to 5 participated in this cross-sectional study. RESULTS: Patients who had reached an advanced CKD stage experienced an increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activity. Plasma homocysteine, cysteine, and IS concentrations were all positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting for potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS, and GSH-Px levels were significantly associated with kidney function, only plasma IS levels still had a significant association with kidney function after these parameters were simultaneously adjusted. In addition, plasma IS could interact with GSH-Px activity to be associated with kidney function. CONCLUSIONS: IS plays a more dominant role than homocysteine and GSH-Px activity in relation to kidney function.

The next generation beneficial actions of novel probiotics as potential therapeutic targets and prediction tool for metabolic diseases.

The prevalence of metabolic disease has rising and affected over 1,000 million populations globally. Since the metabolic disease and its related complication are board, it has become the major health hazard of modern world. However, Long term medication of metabolic disease may cause serious side effects and risk for adverse health problems. Recently, emerging studies focus on exploring the mechanistic details of metabolic state in disease development and progression. Gut bacteria ecosystem was considered to play a pivotal role in regulating energy homeostasis and great associated with the development of metabolic disease. Accumulated evidences indicated that Akkermansia muciniphila, Faecalibacterium prausnitzii, and Roseburia hominis improve the balance of the microecology in the intestine of the host and have positive effects on enhancing nutrients absorption. Hence, the novel probiotics as therapeutic target to modify gut microbiota generally focus on improving microbiota dysbiosis, and offers new prospects for treating metabolic disease. In the present review, we discuss the significant roles and regulatory properties of specific bacterium in the context of intestinal microbial balance, explores the kinds of harmful/beneficial bacteria that were likely to act as indicator for metabolic disease. Further proposed a stepwise procedure in the basis of sequencing technology with that of innovative option to reestablish the microbial equilibrium and prevent metabolic disease.

Reduction of invasion and cell stemness and induction of apoptotic cell death by Cinnamomum cassia extracts on human osteosarcoma cells.

Cinnamomum cassia possesses antioxidative activity and induces the apoptotic properties of various cancer types. However, its effect on osteosarcoma invasion and cancer stemness remains ambiguous. Here, we examined the molecular evidence of the anti-invasive effects of ethanoic C. cassia extracts (CCE). Invasion and migration were obviously suppressed after the expression of urokinase-type plasminogen activator and matrix metalloprotein 2 in human osteosarcoma 143B cells were downregulated. CCE reversed epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor ß1 and downregulated mesenchymal markers, such as snail-1 and RhoA. CCE suppressed self-renewal property and the expression of stemness genes (aldehyde dehydrogenase, Nanog, and CD44) in the 143B cells. CCE suppressed cell viability, reduced the colony formation of osteosarcoma cancer cells, and induced apoptotic cell death in the 143B cells, as indicated by caspase-9 activation. The xenograft tumor model of immunodeficient BALB/c nude mice showed that CCE administered in vivo through oral gavage inhibited the growth of implanted 143B cells. These findings indicated that CCE inhibited the invasion, migration, and cancer stemness of the 143B cells. CCE reduced proliferation of 143B cell possibly because of the activation of caspase-9 and the consequent apoptosis, suggesting that CCE is a potential anticancer supplement for osteosarcoma.

The Interaction between Exercise and Marital Status on Depression: A Cross-Sectional Study of the Taiwan Biobank.

Few studies evaluating the relationship between depression and exercise consider peoples' socio-demographic characteristics. This cross-sectional study investigated the interaction between exercise and marital status and depression in Taiwanese adults. Data from the 2-item Patient Health Questionnaire (PHQ-2) was recruited from the Taiwan Biobank. Participants indicated their exercise status, showing 5015 no-exercise cases and 3407 exercise cases. Marital status, including unmarried, divorced or separated, and widowed, were all significant, especially among the no-exercise group. The relationship between exercise/no exercise and marital status was examined; no exercise and unmarried, divorced or separated, and widowed, as well as exercise and married were significant to PHQ-2. Gender was significant in both the married and unmarried groups. The association between exercise, marital status, gender, and education on PHQ-2 score was also significant. Married people, especially men, had lower depression scores. Additionally, exercise had a protective effect against depression for unmarried people, especially women.

The Prognostic Role of Glutathione and Its Related Antioxidant Enzymes in the Recurrence of Hepatocellular Carcinoma.

The imbalance of high oxidative stress and low antioxidant capacities is thought to be a significant cause of the development and progression of hepatocellular carcinoma (HCC). However, the impact of oxidative stress, glutathione (GSH), and its related antioxidant enzymes on the recurrence of HCC has not been investigated. The purpose of this study was to compare the changes to oxidative stress and GSH-related antioxidant capacities before and after tumor resection in patients with HCC recurrence and non-recurrence. We also evaluated the prognostic significance of GSH and its related enzymes in HCC recurrence. This was a cross-sectional and follow-up study. Ninety-two HCC patients who were going to receive tumor resection were recruited. We followed patients' recurrence and survival status until the end of the study, and then assigned patients into the recurrent or the non-recurrent group. The tumor recurrence rate was 52.2% during the median follow-up period of 3.0 years. Patients had significantly lower plasma malondialdehyde level, but significantly or slightly higher levels of GSH, glutathione disulfide, trolox equivalent antioxidant capacity, glutathione peroxidase (GPx), and glutathione reductase (GR) activities after tumor resection compared to the respective levels before tumor resection in both recurrent and non-recurrent groups. GSH level in HCC tissue was significantly higher than that in adjacent normal tissue in both recurrent and non-recurrent patients. Decreased plasma GPx (HR = 0.995, p = 0.01) and GR (HR = 0.98, p = 0.04) activities before tumor resection, and the increased change of GPx (post-pre-resection) (HR = 1.004, p = 0.03) activity were significantly associated with the recurrence of HCC. These findings suggest there might be a possible application of GPx or GR as therapeutic targets for reducing HCC recurrence.

Rutin and Gallic Acid Regulates Mitochondrial Functions via the SIRT1 Pathway in C2C12 Myotubes.

Mitochondria are highly dynamic organelles, balancing synthesis and degradation in response to increases in mitochondrial turnover (i.e., biogenesis, fusion, fission, and mitophagy) and function. The aim of this study was to investigate the role of polyphenols in the regulation of mitochondrial functions and dynamics in C2C12 myotubes and their molecular mechanisms. Our results indicate that gallic acid and rutin are the most potential polyphenol compounds in response to 15 phenolic acids and 5 flavonoids. Gallic acid and rutin were associated with a significantly greater mitochondrial DNA (cytochrome b and COX-II), mitochondrial enzymatic activities (including citrate synthase and cytochrome c oxidase), and intracellular ATP levels in C2C12 myotubes. Moreover, gallic acid and rutin significantly increased the gene expressions of mitochondrial turnover in C2C12 myotubes. Our findings indicated that gallic acid and rutin may have a beneficial effect on mitochondrial dynamics via regulation of the SIRT1-associated pathway in C2C12 myotubes.

Gossypol Reduces Metastasis and Epithelial-Mesenchymal Transition by Targeting Protease in Human Cervical Cancer.

Metastasis is the most prevalent cause of cancer-associated deaths amongst patients with cervical cancer. Epithelial-mesenchymal transition (EMT) is essential for carcinogenesis, and it confers metastatic properties to cancer cells. Gossypol is a natural polyphenolic compound with anti-inflammation, anti-oxidant, and anticancer activities. In this study, we investigated the antimetastatic and antitumour effects of gossypol on human cervical cancer cells (HeLa and SiHa cells). Gossypol exerted a strong inhibition effect on the migration and invasion of human cervical cancer cells. It reduced the focal adhesion kinase (FAK) pathway-mediated expression of matrix metalloproteinase-2 and urokinase-type plasminogen activator, subsequently inhibiting the invasion of SiHa cells. In addition, gossypol reversed EMT induced by transforming growth factor beta 1 (TGF-[Formula: see text]1) and up-regulated epithelial markers, such as E-cadherin but significantly suppressed Ras homolog family member (Rho)A, RhoB, and p-Samd3. The tail vein injection model showed that gossypol treatment via oral gavage reduced lung metastasis. Gossypol also decreased tumour growth in vivo in the nude mouse xenograft model. All these findings suggest that gossypol suppressed the invasion and migration of human cervical cancer cells by targeting the FAK signaling pathway and reversing TGF-[Formula: see text]1-induced EMT. Hence, gossypol warrants further attention for basic mechanistic studies and drug development.

Effect of Astaxanthin on the Inhibition of Lipid Accumulation in 3T3-L1 Adipocytes via Modulation of Lipogenesis and Fatty Acid Transport Pathways.

Obesity is defined as a condition of excessive fat tissue accumulation. It was the major factor most closely associated with lifestyle-related diseases. In the present study, we investigated the effect of astaxanthin on the inhibition of lipid accumulation in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with 0-25 µg/mL of astaxanthin for 0-48 h. The result indicated that astaxanthin significantly decreased the oil Red O stained material (OROSM), intracellular triglyceride accumulation, and glycerol 3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 adipocytes (p < 0.05). At the molecular level, astaxanthin significantly down-regulated the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) in 3T3-L1 adipocytes (p < 0.05). Moreover, target genes of PPARγ on the inhibition of lipogenesis, such as Acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), fatty acid binding protein (aP2), cluster of differentiation 36 (CD36), and lipoprotein lipase (LPL) in 3T3-L1 adipocytes were significantly down-regulated at a time-dependent manner (p < 0.05). These results suggested that astaxanthin efficiently suppressed lipid accumulation in 3T3-L1 adipocytes and its action is associated with the down-regulation of lipogenesis-related genes and the triglyceride accumulation in 3T3-L1 adipocytes. Therefore, astaxanthin can be developed as a potential nutraceutical ingredient for the prevention of obesity in a niche market.

Implementation of nutrition practice improves growth velocity and weight gain in premature infants ≤ 1250 grams.

BACKGROUND: The concept of parental nutritional care for premature infants has been applied and advanced over the past decade. This study compared the clinical outcomes before and after nutrition practice (NP) implementation and evaluated the effects of implementation on growth velocity and weight gain in premature infants. METHODS: Descriptive data of premature infants (gestational age < 30 weeks; body weight ≤ 1250 g) born 4 years before and after NP implementation were retrospectively reviewed in a neonatal intensive care unit at a hospital in Taiwan. Nutrient intake, growth velocity, weight gain, and nutrition-related biochemical markers were compared at weeks 1, 2, and 4 after delivery. RESULTS: A total of 77 premature infants were enrolled before NP implementation (non-NP group), whereas 89 were enrolled after implementation (NP group). The non-NP group consumed less fat and energy in week 1, and less protein, fat, and energy in weeks 2 and 4 compared with the NP group. Growth velocity was slower in the non-NP group. Fat intake was significantly positively correlated with body weight at week 4 in the non-NP group. However, protein and fat intake were significantly associated with body weight at week 1, fat and energy intakes were significantly associated with body weight at week 2, and fat intake was significantly associated with body weight at week 4 in the NP group. CONCLUSION: These findings indicate that the NP implemented in this study is relatively safe and can improve growth velocity and body weight gain in premature infants.

Higher glutathione demand may be necessary for assisting haemodialysis patients to cope with increased oxidative stress.

AIM: The removal of cysteine during a dialysis procedure may affect glutathione (GSH) concentration, allowing haemodialysis (HD) patients to become more susceptible to oxidative damage. This study was performed to determine whether the change of GSH/glutathione disulfide (GSSG) redox state and GSH redox potential were linked with the change of cysteine or oxidative stress in patients receiving HD treatment. METHODS: Sixty-seven HD patients who had received regular HD treatment were recruited. Plasma GSH, GSSG, cysteine and malondialdehyde (MDA) were measured at both pre- and post-HD. RESULTS: Plasma cysteine, GSH and GSSG levels significantly decreased after the completion of HD, compared to the levels at pre-HD. Plasma MDA concentration, GSH/GSSG ratio and GSH redox potential remained constant during the dialysis session. Plasma GSH and GSSG were positively associated with plasma MDA at post-HD, while GSH redox potential was negatively associated with plasma MDA at post-HD. However, plasma GSH, GSSG, GSH/GSSG ratio and GSH redox potential were not associated with plasma cysteine at either pre- or post-HD. CONCLUSION: The GSH and GSSG levels were significantly utilized during a HD session, and their levels were significantly associated with increased oxidative stress. HD patients may require higher GSH demands to cope with increased oxidative stress during an HD session.

Plasma Homocysteine and Glutathione Are Independently Associated With Estimated Glomerular Filtration Rates in Patients With Renal Transplants.

BACKGROUND: Elevated levels of plasma homocysteine could, through homocysteine oxidation, induce the overproduction of reactive oxygen species, leading to a reduction in glutathione-related antioxidants, and may impair graft functions in patients with renal transplants. The purpose of this study was to determine whether plasma homocysteine, glutathione, or its related antioxidants were related to graft functions in patients with renal transplants. PATIENTS AND METHODS: We recruited 66 patients (mean age 48.4 years) with renal transplants (mean transplant duration 8.3 years). Patients were divided into 2 groups, based on their estimated glomerular filtration rate (eGFR): the moderate graft function group (eGFR ≥ 60 mL/min/1.73 m2, n = 37) and low graft function group (eGFR < 60 mL/min/1.73 m2, n = 29). We then determined their fasting levels of the following: malondialdehyde (MDA), homocysteine, cysteine, pyridoxal 5'-phosphate (PLP), glutathione (GSH), oxidized glutathione (GSSG), GSH/GSH ratio, glutathione peroxidase (GSH-Px) activity. RESULTS: We found in the low graft function group significantly higher levels of plasma homocysteine, cysteine, GSH, and GSH/GSSG ratios. But an intergroup difference was not found regarding levels of MDA, PLP, GSSG, and GSH-Px activity. After adjusting for potential confounders, the increased plasma homocysteine and GSH levels were independently associated with lower eGFR. No interaction existed between homocysteine and GSH levels in association with eGFR. CONCLUSION: Increased plasma homocysteine and GSH levels appeared to be independent indicators of decreased graft functions in patients with renal transplants.

Possible Synergistic Effects of Glutathione and C-Reactive Protein in the Progression of Liver Cirrhosis.

Liver cirrhosis is often associated with increased inflammatory responses and changes of glutathione (GSH) status. The possible interactions between these two factors in mediating damages of liver function remain unclear. Here, we measured the inflammatory responses and GSH status in liver cirrhotic patients and compared them with healthy subjects. In addition, we assessed the relationship of the GSH status and levels of inflammatory markers with the severity of the disease. This was a cross-sectional study. In total, we recruited 63 liver cirrhotic patients with Child⁻Turcotte⁻Pugh class A scores, and 12 patients with class B⁻C scores, together with 110 healthy subjects. Patients with class B⁻C scores showed the highest level of high-sensitivity C-reactive protein (hs-CRP) when compared with class A patients or healthy subjects. Patients in class A group had significantly higher GSH levels when compared with class B⁻C group or healthy subjects. After adjusting for potential confounders and each other, serum hs-CRP levels showed positive association with the Child⁻Turcotte⁻Pugh scores, while GSH levels showed negative association with Child⁻Turcotte⁻Pugh scores. Interactions were found between levels of plasma GSH and serum hs-CRP (ß = 0.004, p = 0.016). CRP and GSH levels, which had showed interactions, were associated with the severity of liver cirrhosis.

Vitamin B-6, Independent of Homocysteine, Is a Significant Factor in Relation to Inflammatory Responses for Chronic Kidney Disease and Hemodialysis Patients.

The purpose of this study was to investigate whether plasma pyridoxal 5'-phosphate (PLP) and homocysteine were dependent on or independent of each other in order to be associated with inflammatory markers in patients with chronic kidney disease (CKD) or those receiving hemodialysis treatment. This was a cross-sectional study. Sixty-eight stage 2-5 CKD patients and 68 hemodialysis patients had one time fasting blood drawn for measurements of plasma PLP, pyridoxal (PL), homocysteine, and several inflammatory markers. Early CKD stage (stages 2-3) patients showed significantly lower plasma PLP levels and homocysteine concentrations than patients in an advanced CKD stage (stages 4-5) and those undergoing hemodialysis. Plasma PLP significantly correlated with CRP levels (partial rs = -0.21, p < 0.05) and plasma PL significantly correlated with IL-10 levels (partial rs = -0.24, p < 0.01), while plasma PLP plus PL significantly correlated with both CRP levels (partial rs = -0.20, p < 0.05) and interleukin-1ß (partial rs = 0.22, p < 0.05) levels after adjusting for plasma homocysteine and other potential confounders. Plasma homocysteine displayed no significant correlations with any inflammatory markers. Vitamin B-6 status, rather than homocysteine, appeared to be a significant factor in relation to inflammatory responses for CKD and hemodialysis patients.

Vitamin B-6 Supplementation Could Mediate Antioxidant Capacity by Reducing Plasma Homocysteine Concentration in Patients with Hepatocellular Carcinoma after Tumor Resection.

Vitamin B-6 has a strong antioxidative effect. It would be useful to determine whether vitamin B-6 supplementation had effects on antioxidant capacities in patients with hepatocellular carcinoma (HCC) who had recently undergone tumor resection. Thirty-three HCC patients were randomly assigned to either the placebo (n = 16) group or the vitamin B-6 50 mg/d (n = 17) group for 12 weeks. Plasma pyridoxal 5'-phosphate, homocysteine, indicators of oxidative stress, and antioxidant capacities were measured. Plasma homocysteine in the vitamin B-6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC) was significantly increased at the end of the intervention period. Vitamin B-6 supplementation had a significant reducing effect on the change of plasma homocysteine (ß = -2.4, p = 0.02) but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (ß = -162.0, p = 0.03). Vitamin B-6 supplementation seemed to mediate antioxidant capacity via reducing plasma homocysteine rather than having a direct antioxidative effect in HCC patients who had recently undergone tumor resection. The clinical trial number is NCT01964001, ClinicalTrials.gov.