Reactive Oxygen Species Levels In Tissues Research Articles

1,25(OH)2D3 inhibits pancreatic stellate cells activation and promotes insulin secretion in T2DM.

To evaluate the effect and mechanism of 1,25(OH)2D3 on pancreatic stellate cells (PSCs) in type 2 diabetes mellitus (T2DM). A mouse model of T2DM was successfully established by high-fat diet (HFD) /streptozotocin (STZ) and administered 1,25(OH)2D3 for 3 weeks. Fasting blood glucose (FBG), glycated hemoglobin A1c (GHbA1c), insulin (INS) and glucose tolerance were measured. Histopathology changes and fibrosis of pancreas were examined by hematoxylin and eosin staining and Masson staining. Mouse PSCs were extracted, co-cultured with mouse insulinoma β cells (MIN6 cells) and treated with 1,25(OH)2D3. ELISA detection of inflammatory factor expression. Tissue reactive oxygen species (ROS) levels were also measured. Immunofluorescence or Western blotting were used to measure fibrosis and inflammation-related protein expression. PSCs activation and islets fibrosis in T2DM mice. Elevated blood glucose was accompanied by significant increases in serum inflammatory cytokines and tissue ROS levels. 1,25(OH)2D3 attenuated islet fibrosis by reducing hyperglycemia, ROS levels, and inflammatory factors expression. Additionally, the co-culture system confirmed that 1,25(OH)2D3 inhibited PSCs activation, reduced the secretion of pro-inflammatory cytokines, down-regulated the expression of fibrosis and inflammation-related proteins, and promoted insulin secretion. Our findings identify that PSCs activation contributes to islet fibrosis and β-cell dysfunction. 1,25(OH)2D3 exerts beneficial effects on T2DM potentially by inhibiting PSCs activation and inflammatory response, highlighting promising control strategies of T2DM by vitamin D.

Effects of Pemafibrate on Reducing Oxidative Stress and Augmenting Angiogenesis in Ischemic Limb Tissue.

Oxidative damage is observed in the ischemic limbs of patients with arteriosclerosis obliterans. We investigated whether pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, reduced oxidative stress in ischemic limbs and consequently rescued limb damage in model mice. We surgically induced hind-limb ischemia in mice and orally administered pemafibrate solution (P-05 group, 0.5 mg/kg/day; P-10 group, 1.0 mg/kg/day) or control solution (control group). Seven days after the surgery, differences in reactive oxygen species (ROS) contents, antioxidative enzyme and transcription factor expression, blood flow, and capillary density in ischemic limbs were assessed. Tissue ROS levels were lower in the P-05 and P-10 groups compared with those in the control group. Although the tissue expression levels of nuclear factor-erythroid 2-related factor 2 increased in the P-10 group compared with that in the control group, no corresponding changes were observed in the tissue expression of four antioxidative enzymes. The limb salvage rates and capillary densities in ischemic limbs were higher in the P-05 and P-10 groups than that in the control group. Pemafibrate treatment reduced oxidative stress and augmented angiogenesis in ischemic limbs, contributing to prevention of limb damage in mice.

P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology.

Reactive oxygen species (ROS) dysregulation exacerbates many pathologies but must remain within normal ranges to maintain cell function. Since ROS-mediated pathology and routine cell function are coupled, in vivo models evaluating low-ROS background effects on pathology are limited. Some models alter enzymatic antioxidant expression/activity, while others involve small molecule antioxidant administration. These models cause non-specific ROS neutralization, decreasing both beneficial and detrimental ROS. This is detrimental in cardiovascular pathology, despite the negative effects excessive ROS has on these pathologies. Thus, current trends in ROS-mediated pathology have shifted toward selective inhibition of ROS producers that are dysregulated during pathological insults, such as p66Shc. In this study, we evaluated a zebrafish heterozygote p66Shc hypomorphic mutant line as a low-ROS myocardial infarction (MI) pathology model that mimics mammalian MI. Our findings suggest this zebrafish line does not have an associated negative phenotype, but has decreased body mass and tissue ROS levels that confer protection against ROS-mediated pathology. Therefore, this line may provide a low-ROS background leading to new insights into disease.

Transient responses of melatonin to stress

Melatonin and its metabolites are ubiquitous antioxidants that are produced
 in response to reactive oxygen species (ROS) in virtually all cells of the
 body. The highest reported melatonin values in plasma and sweat occur during
 heavy exercise both indoors and outdoors during the day. The advent of sweat
 biosensors with sufficient melatonin sensitivity provides pseudo real-time
 evidence that melatonin is produced throughout the body not just in the pineal
 gland. The role of the pineal gland appears to be to provide cyclic production
 of melatonin for the regulation of circadian rhythms as well as supplemental melatonin
 during periods of low cellular activity. 
 Melatonin from the pineal gland represents only a small fraction of the
 body’s production capacity. Greater than 5 pg/ml min ramp rates for plasma and
 sweat melatonin have been reported during strenuous exercise in sunlight as
 compared to 0.15 pg/ml min ramp rates for plasma melatonin under dim light
 melatonin onset (DLMO) conditions. Sunlight
 and exercise, like fever, generates transient elevated levels of ROS in tissues
 with time constants measured in minutes or even seconds making this systemic
 antioxidant response potentially protective. Based on a simple accounting of
 ROS generated by sunlight, ROS we breathe, ROS we drink, and exercise, it
 appears that the body maintains a heightened basal level of ROS as part of its
 pathogen defense mechanisms. Current
 human lifestyles and modern enclosed spaces have substantially eliminated over
 90% of the ROS which undermines one of the body’s primary defenses. With
 advanced age, the inability to maintain this protective barrier appears to make
 us more susceptible to disease.

Role of reactive oxygen species in gestational diabetes and the impact on the developing fetus

Gestational diabetes mellites (GDM) is characterized by elevated levels of glucose in a pregnant woman's bloodstream that occurs from an overproduction of hormones. Under GDM, elevated glucocorticoids (GC) and insulin like growth factor (IGF)‐1 hormones in the placenta may possibly lead to an increase in the amount of reactive oxygen species (ROS) in the embryo due to an increase in glucose utilization and mitochondrial activity. Overproduction of ROS can modify the genome, thus predisposing offspring's to diabetes and obesity later. The aim of the study is to investigate the mechanism by which GDM leads to an increased production of ROS and evaluate the epigenetic changes that occur. I hypothesize that under diabetic conditions, the embryo will have an increase in ROS production due to increased hormone levels, resulting in epigenetic changes in the offspring. An in vivo model for GDM will be established by feeding female mice a high‐fat diet for four weeks. Controls will be fed a standard diet. Fasting blood glucose levels and glucose tolerance tests will monitor the development of diabetes. Mating between a diabetic or control female will occur with a normal male. At 6.5 and 17.5 days of gestation and 7 days post birth, maternal, fetal and placental blood and tissue will be collected. Biochemical assays will evaluate tissue ROS levels and epigenetic changes. Blood analysis will measure hormone and glucose levels. Results from this study will hopefully lead to the development of treatments to lower the incidence of diabetes in future generations.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Potato chip intake increases ascorbic acid levels and decreases reactive oxygen species in SMP30/GNL knockout mouse tissues.

Potato chips (PC) contain abundant amounts of the free radical scavenger ascorbic acid (AA) due to the rapid dehydration of potato tubers (Solanum tuberosum) that occurs during frying. To evaluate the antioxidant activity of PC, this study examined reactive oxygen species (ROS) levels in tissues from SMP30/GNL knockout (KO) mice that cannot synthesize AA and determined AA and ROS levels after the animals were fed 20 and 10% PC diets for 7 weeks. Compared with AA-sufficient mice, AA-depleted SMP30/GNL KO mice showed high ROS levels in tissues. SMP30/GNL KO mice fed a PC diet showed high AA and low ROS levels in the brain, heart, lung, testis, soleus muscle, plantaris muscle, stomach, small intestine, large intestine, eyeball, and epididymal fat compared with AA-depleted mice. The data suggest that PC intake increases AA levels and enhances ROS scavenging activity in tissues of SMP30/GNL KO mice, which are a promising model for evaluating the antioxidant activity of foods.

Role of Reactive Oxygen Species During Hypertension in Response to Chronic Antiangiogenic Factor (sFlt-1) Excess in Pregnant Rats

Preeclampsia is associated with increased levels of reactive oxygen species (ROS) and the antiangiogenic factor, soluble fms-like tyrosine kinase-1 (sFlt-1). Moreover, recent studies have indicated that chronic sFlt-1 excess causes hypertension in pregnant animals. The purpose of this study was to evaluate the role of ROS in mediating sFlt-1-induced hypertension in the pregnant rat. Mean arterial pressure (MAP), and plasma sFlt-1 and tissue ROS levels were measured in the following groups: (i) pregnant controls; (ii) sFlt-1-treated pregnant rats; (iii) Tempol-treated pregnant rats; (iv) sFlt-1- and Tempol-treated pregnant rats. MAP increased from 104 ± 2 mm Hg in pregnant control rats to 118 ± 3 mm Hg (P = 0.002) in sFlt-1-infused rats. Basal and nicotinamide adenine dinucleotide phosphate (NADPH)-stimulated levels of tissue ROS were increased in response to excess sFlt-1 during pregnancy. Pretreatment with Tempol attenuated oxidative stress and hypertension in response to sFlt-1. ROS play an important role in mediating hypertension in response to chronic sFlt-1 excess during pregnancy.

Targeting reactive oxygen species in hypertension

Hypertension is a major risk factor for vascular diseases such as stroke, myocardial infarction, and renal microvascular disease. The mechanism by which vascular disease develops is complex, and growing evidence suggests that an increase in reactive oxygen species during hypertension is a major contributing factor. NADPH oxidase, the primary source of reactive oxygen species in the cardiovascular system, is a strong candidate for the development of therapeutic agents to ameliorate hypertension and end-organ damage. Various scavengers and inhibitors of reactive oxygen species have been proposed for use in animal as well as human studies. While many of these agents are effective at lowering tissue reactive oxygen species levels, their specificity is a serious concern. Our laboratory has developed cell-permeant peptidic inhibitors targeting key interactions among the different NAD(P)H oxidase homologues. One of these inhibitors targeting nox2 and p47-phox interaction has proven useful in attenuating target neoplasia and hypertrophy. Strategies aimed at specifically inhibiting NAD(P)H oxidase have proven effective in attenuating cardiovascular oxidative stress. The development of new inhibitors targeting novel oxidase homologues appears to hold significant promise for clarifying the physiologic role of these homologues as well as for the development of new antioxidant therapies.