Effect of Indoxyl Sulfate on Oxidative Stress, Apoptosis, and Monocyte Chemoattractant Protein-1 in Leukocytes

This study showed that indoxyl sulfate, an uremic toxin present in the serum of patients with chronic kidney disease, increases oxidative stress and apoptosis in human neutrophils and reduces the production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cell (PBMC). It is possible that these effects caused by this toxin contribute to vascular injury of the endothelium and decreased response to infectious insults, respectively.

Tualang Honey Supplementation Reduces Blood Oxidative Stress Levels/Activities in Postmenopausal Women

This study aimed to investigate the ability of Tualang honey (TH), a phytoestrogen, to reduce blood oxidative stress levels/activities in postmenopausal women and compared the effects with the standard estrogen progestin therapy (EPT). A total of 78 healthy postmenopausal women were randomly assigned to one of two groups; EPT group received Femoston conti 1/5 (1 mg 17β-estradiol and 5 mg dydrogesterone), and TH group, received 20 g of TH supplement daily for 16 weeks. The reduced glutathione to oxidized glutathione ratio (GSH : GSSG), plasma glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and 4-hydroxynonenal (4-HNE) levels/activities were measured at pre- and postinterventions using commercially available kits. The plasma GPx and CAT activities were notably increased, and plasma 4-HNE level was significantly decreased in postmenopausal women who received EPT and TH supplementation. TH supplementation for 16 weeks was able to reduce blood oxidative stress levels/activities of postmenopausal women comparable to those who received EPT. Thus, TH has a potential to be used as antioxidant therapy to combat oxidative stress-induced neurodegenerative diseases. This trial is registered with NCT01300676.

Plasma Aminothiol Profile and Some of Its Determinants in Apparently Healthy Azorean Subjects

Objectives. To evaluate the plasma aminothiol profile (PAP) and serum gamma-glutamyltransferase (GGT) activity, as well as plasma folate, vitamin B12, and vitamin B6 concentrations, in 326 apparently healthy subjects from the Azores archipelago (Portugal). Also eventual relationships of PAP with conventional risk factors for atherosclerosis were investigated, aiming at the finding of early blood markers of the disease. Design and Methods. This was an observational cross-sectional study, where participants were split into two groups: one with a normal and another with an altered PAP (at least one aminothiol out of its reference concentration range). Results. About 76% of subjects had an altered PAP, mainly due to low glutathione levels (<1.5 μmol/L), mostly associated with normal GGT activity. Prevalence of hyperhomocysteinemia was 10%, where only 33% had some B-vitamin deficiency. The risk for atherosclerosis was more evidenced in subjects exhibiting both deficient GSH concentration and increased serum GGT activity. Conclusions. An altered PAP, namely, when caused by low GSH levels in the absence of alterations in the Hcy, or Cys, or Cys-Gly concentrations and in serum GGT activity, might reveal a subclinical stage of atherogenesis and should be explored as a potential early marker of atherosclerosis.

Heme Consumption Reduces Hepatic Triglyceride and Fatty Acid Accumulation in a Rat Model of NAFLD Fed Westernized Diet

Studies have identified that serum-free hemoglobin subunits correlate positively with the severity of nonalcoholic fatty liver disease (NAFLD). However, the role of hemoglobin in the development of NAFLD remains unclear. In the present study, a rat model of NAFLD was developed, using a westernized diet high in saturated fat and refined sugar. Since a “westernized” diet is also high in red meat, we tested the effect of hemoglobin as a dietary source of heme in our model. Sprague-Dawley rats were fed ad libitum for 4 weeks either control diet (7% fat), westernized diet (WD, 18% fat + 1% cholesterol), hemoglobin diet (7% fat + 2.5% Hb), or westernized and hemoglobin diet (18% fat + 1% cholesterol + 2.5% Hb). Rats fed WD developed features of NAFLD, including insulin resistance and accumulation of liver fatty acids in the form of triglycerides, increased lipid peroxidation (F2-Isoprostanes), and liver fibrotic marker (hydroxyproline). Hemoglobin consumption significantly influenced several biomarkers of NAFLD and hepatic biochemistry, suggesting a possible interaction with diet and/or liver lipid pathways. The complex mechanisms of interaction between WD and hemoglobin in our rat model warrants further studies to examine the role of dietary heme on NAFLD.

Carbofuran Induced Oxidative Stress in Rat Heart: Ameliorative Effect of Vitamin C

The aim of this study was to evaluate the effect of carbofuran on the levels of certain biomarkers in heart of rat exposed to sublethal concentrations of pesticide for 30 days after each interval of 24 h. The ameliorative effect of vitamin C by pretreatment of rats was also monitored. The results indicated that the activities of acetylcholinesterase and lactate dehydrogenase (LDH) decreased significantly in rat heart tissues, the extent of inhibition being concentration dependent. In contrast, the level of LDH increased in serum. The levels of malondialdehyde, total thiols, and glutathione were significantly elevated whereas the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione-S-transferase were remarkably decreased in rat heart tissues. The serum concentrations of cholesterol increased by 47 and 77% and high density lipids decreased by 35 and 64%, respectively, due to exposure to 5 and 10% LD50 of carbofuran. The prior treatment of rats with vitamin C (100 mg kg−1 body weight) exerted significant ameliorative effect. The recovery was higher at low carbofuran concentration (5%) tested. The results indicated that carbofuran induced oxidative stress and caused damage to cardiac tissues, which could be recovered by prior application of vitamin C.

Beneficial Regulation of Elastase Activity and Expression of Tissue Inhibitors of Matrixmetalloproteinases, Fibrillin, Transforming Growth Factor-β, and Heat Shock Proteins by P. leucotomos in Nonirradiated or Ultraviolet-Radiated Epidermal Keratinocytes

There is loss of the structural integrity of the extracellular matrix (ECM) with intrinsic aging as well as photoaging, largely due to reactive oxygen species (ROS). The structural ECM proteins include the microfibrils that are composed of fibrillin. The structural ECM proteins are primarily degraded by the matrixmetalloproteinases (MMPs) and elastase enzymes. The MMPs are inhibited by the tissue inhibitors of MMPs (TIMPs). A primary regulator of the ECM proteins is transforming growth factor-β (TGF-β), and the chaperone proteins important for its formation are the heat shock proteins (HSP). P. leucotomos extract beneficially regulates of MMPs, TIMPs, and TGF-β in nonirradiated or ultraviolet (UV) radiated fibroblasts and melanoma cells. The hypothesis of this research was that the antioxidant activity or chemistry of P. leucotomos extract would also directly inhibit elastase activity, stimulate the cellular expression of TIMPs, fibrillins, and TGF-β, and regulate HSPs in nonirradiated and UVA or UVB radiated epidermal keratinocytes. P. leucotomos directly inhibited elastase activity, stimulated the cellular expression of TIMPs, fibrillins, and TGF-β, and differentially regulated HSPs in nonirradiated and UVA or UVB radiated epidermal keratinocytes. We infer that the P. leucotomos extract strengthens the ECM and is effective in the prevention or treatment of intrinsic and photoaging of skin.

Amelioration of Sarcoptic Mange-Induced Oxidative Stress and Apoptosis in Dogs by Using Calendula officinalis Flower Extracts

Twenty-four clinically Sarcoptes-infested dogs were randomly enrolled into three groups (groups A, B, and C), 8 dogs in each group. Group A was treated with ivermectin + Calendula officinalis flower extract (CFE). Group B was treated with ivermectin + N-acetyl cysteine (NAC) (standard positive controls), while group C (negative control) was treated with ivermectin alone. Another eight healthy dogs were used as healthy controls (group D). By day 28 after therapy, the dogs treated adjunctly with CFE as well as with N-acetyl cysteine revealed significant () amelioration of the altered markers of oxidative stress towards normalcy. The dogs of these groups also revealed significant () amelioration of apoptotic leukocytes towards normalcy, and values were comparable to those of the healthy controls. While by day 28 after therapy, ivermectin alone treated dogs could not achieve comparable values to those of the healthy controls. The dogs treated adjunctly with CFE and N-acetyl cysteine also revealed faster parasitological as well as clinical cure rate as compared to the ivermectin alone treated dogs. In conclusion, CFE has remarkable antioxidant and antiapoptotic potential and can constitute a potential adjunctive remedy with miticide for the therapeutic management of canine sarcoptic mange.

Vasculotoxic and Proinflammatory Effects of Plasma Heme: Cell Signaling and Cytoprotective Responses

The proinflammatory vasculotoxic effects of intravascular hemolysis are modulated by plasma hemoglobin and heme clearance via the haptoglobin/CD163 system and the hemopexin/CD91 system, respectively, and detoxification through the heme oxygenase/ferritin system. However, sudden or excessive hemolysis can overwhelm these protective systems leading to heme interacting with cells of the vasculature. Heme presents a damage-associated molecular pattern to the innate immune system. Heme is an extracellular inflammatory signaling molecule with strict binding specificity for TLR4 on monocyte/macrophages, endothelial, and other cells. The resulting TLR4 signaling cascade rapidly leads to intracellular oxidative stress and an inflammatory response. Heme also induces a cytoprotective response that includes Nrf2 responsive genes such as heme oxygenase-1, ferritin, haptoglobin, hemopexin, and other antioxidant response genes. It is the balance between the pro-inflammatory/vasculotoxic effects of plasma hemoglobin/heme and the cytoprotective responses that ultimately determines the pathophysiologic outcome in patients.

Sea Buckthorn Pulp Oil Treatment Prevents Atherosclerosis in Obese Children

This study aimed to determine the effects of sea buckthorn pulp oil treatment (800 mg/day for 60 days) on inflammatory, systemic oxidative/reductive status and endothelial function, in obese children. A total of 41 obese children (10–18 years old) and thirty controls were enrolled. The measurements were done before and after pulp oil administration. Ultrasounds were used for flow-mediated dilatation (FMD) and carotid artery intima-media thickness (IMT) measurements and colorimetric and ELISA methods for biochemical parameters. In the obese children versus the lean ones, increased oxidative stress (high malonyldialdehyde, high respiratory burst (RB)), low antioxidant defence (low blood glutathione, low TEAC), inflammatory status (high CRP, ceruloplasmin), adipocytokines disturbance (low adiponectin and high leptin), insulin resistance (high fasting C peptide), low FMD (P<0.001), and high IMT (P<0.01) were measured. Treatment reduced total cholesterol (P<0.03), triglycerides (P<0.01), RB (P<0.03), leptin (P<0.049), ceruloplasmin (P<0.01), fasting C peptide (P<0.01), blood pressure (P<0.01), and IMT (P<0.03). In conclusion, sea buckthorn pulp oil treatment prevents atherosclerosis by lowering triglyceridemia, cholesterolemia, and blood pressure (strong effects) and by reducing oxidative stress, inflammation, and insulin resistance (weak effects).