Comparative effects between electronic cigarette and tobacco cigarette smoke on oxidative markers in cultured immune cells isolated from rats.

Background: Tobacco cigarette smoke (TCS) was previously demonstrated to affect the innate and adaptive immune responses as a consequence of oxidant generation which play a pivotal role in neutrophilic airway inflammation. Aim of this paper was to investigate whether electronic cigarette smoke (ECS) generates reactive oxygen species (ROS) similarly to cigarette smoke.

Method: By means of a house made apparatus, ECS and TCS were collected in fetal bovine serum (FBS) which was used to grow immune cells isolated from rats.

The adenosine A receptor agonist T1-11 ameliorates neurovisceral symptoms and extends the lifespan of a mouse model of Niemann-Pick type C disease.

Niemann-Pick C is a fatal neurovisceral disorder caused, in 95% of cases, by mutation of NPC1 gene. Therapeutic options are extremely limited and new "druggable" targets are highly warranted. We previously demonstrated that the stimulation of the adenosine A receptor (AR) normalized the pathological phenotype of cellular models of NPC1.

Eicosapentaenoic acid modulates the synergistic action of CREB1 and ID/E2A family members in the rat pup brain and mouse embryonic stem cells.

The aim of this study was to investigate the molecular mechanism by which eicosapentaenoic acid (EPA) may exert neuroprotective effects through an "EPA-cyclic AMP response element-binding protein (CREB)" signaling pathway. The current study reveals that EPA modulates the exquisite interplay of interaction of CREB1 with the inhibitor of DNA binding (ID) and E2A family members, thereby delivering mechanistic insights into specific neural differentiation program. In this scenario, our work provides evidence for the capability of CREB1 to sequester ID:E2A family members in brain tissues and neural differentiating mouse embryonic stem cells (mESCs) through formation of a [CREB1]:ID2:E47 tetrameric complex.

Ethyl-eicosapentaenoic acid ameliorates the clinical course of experimental allergic encephalomyelitis induced in dark agouti rats.

Eicosapentaenoic acid (EPA), a fatty acid present in high amount in fish, modulates immune response and stimulates myelin gene expression. In the present paper, we investigated the effects of EPA in an established animal model for multiple sclerosis (MS): experimental autoimmune encephalomyelitis (EAE) induced in dark agouti rats. Diets supplemented either with 0.

Micronutrient-enriched rapeseed oils improve the brain oxidant/antioxidant system in rats fed a high-fat diet.

The main proposal of this study was to evaluate in vivo whether micronutrient-enriched rapeseed oils obtained using different crushing and refining procedures and characterized by different quantities and qualities of micronutrients (optimized oils) could have any beneficial effect on the antioxidant status of the brain. Sprague-Dawley rats were fed a high-fat diet for 4 weeks. The lipid source consisted of 20% optimized rapeseed oils with different quantities and qualities of micronutrients.

Micronutrient-enriched rapeseed oils reduce cardiovascular disease risk factors in rats fed a high-fat diet.

Many epidemiological studies have demonstrated that vegetable food consumption is associated with a reduced risk of cardiovascular diseases. The beneficial effects have been attributed to the content of bioactive molecules present in large quantities in plant food. The main proposal of this study was to evaluate in vivo whether micronutrient-enriched rapeseed oils (optimised oils) obtained using different crushing and refining procedures and characterised by different quantities and qualities of micronutrients, could have any beneficial effect on lipid profile and antioxidant status of plasma and liver.

PMP70 knock-down generates oxidative stress and pro-inflammatory cytokine production in C6 glial cells.

By using RNA interference (RNAi) in rat C6 glial cells, we previously generated the cell line abcd3kd in which the peroxisomal half-transporter PMP70 was stably knocked-down. The observations that abcd3kd cells had peroxisomal beta-oxidation impairment and an increase of hexacosenoic acid in cholesterol ester fraction, indicated an overlapping function of PMP70 with adrenoleukodystrophy protein (ALDP), the peroxisomal half-transporters involved in X-linked adrenoleukodystrophy (X-ALD). The objective of the present study was to investigate whether PMP70 could affect some oxidative and inflammatory parameters, since many findings indicate oxidative damage in the brain of ALD patients and inflammation is a hallmark of the cerebral forms of X-ALD.

RNAi-mediated silencing of ABCD3 gene expression in rat C6 glial cells: a model system to study PMP70 function.

The function of PMP70, one of the four ABC half-transporters of mammalian peroxisomes, encoded by ABCD3 gene, is still unclear. The finding that PMP70 over-expression partially corrected very long-chain fatty acid oxidation defects in fibroblasts of X-linked adrenoleukodystrophy patients, has unveiled its potential clinical relevance, prompting us to set up a model system to study PMP70 function. We used the RNA interference technique, a powerful approach to loss-of-function gene expression analysis, to knockdown the ABCD3 gene in the rat glial C6 cell line, since glia could represent the target tissue of X-linked adrenoleukodystrophy disease.

Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain.

We have previously demonstrated that, in C6 glioma cells, eicosapentaenoic acid (EPA) stimulates the expression of proteolipid protein (PLP) via cAMP-mediated pathways. In this study, we investigated whether n-3 polyunsaturated fatty acids can affect myelinogenesis in vivo. A single dose of either EPA or docosahexaenoic acid (DHA) was injected intracerebroventricularly into 2-day-old rats, which were then killed after 3 days post-injection (p.

Docosahexaenoic acid supplementation induces dose and time dependent oxidative changes in C6 glioma cells.

In view of the promising use of n-3 polyunsaturated fatty acids (PUFAs) in the prevention and treatment of neurological diseases, it is necessary to ascertain the lack of detrimental oxidative effects. We evaluated short- and long-term effects of 25, 50 and 75 muM docosahexaenoic acid (DHA) supplementation on the oxidative status of C6 glial cells. DHA was incorporated into cells dose and time dependently without any cytotoxic effect.

Eicosapentaenoic acid stimulates leptin receptor gene expression in the hypothalamus of newborn rats.

Body weight and obesity are controlled by the binding leptin (Ob) receptor, but in newborn rats, despite high Ob levels, hypothalamic leptin receptors (Ob-Rb) are only weakly expressed. In this study we have attempted to stimulate expression of the Ob-Rb gene by administering 2 polyunsaturated fatty acids (PUFAs) recommended for the maternal diet and known as gene regulators: docosahexaenoic acid and eicosapentaenoic acid (EPA). We studied the effects of a single dose injected into a cerebral ventricle of newborn rats on postnatal day 2.

Effect of arachidonic, eicosapentaenoic and docosahexaenoic acids on the oxidative status of C6 glioma cells.

n-3 polyunsaturated fatty acids (PUFAs) have been described to have beneficial effects on brain development and in the prevention and treatment of brain damage. C6 glioma cells were incubated with 100 microM of either C20:4n-6 (ARA), or C20:5n-3 (EPA), or C22:6n-3 (DHA) for different time periods to assess whether these acids altered the cellular oxidative state. The ARA and EPA were promptly metabolised to C22:4n-6 and C22:5n-3, respectively, whereas DHA treatment simply increased the amount of DHA in the cells.

Effects of L-mono methyl-arginine, N-acetyl-cysteine and diphenyleniodonium on free radical release in C6 glial cells enriched in hexacosenoic acid.

Previously, we have shown that C6 glial cells enriched in hexacosenoic acid (HA) incubated with oxidative stressors released higher amounts of nitric oxide (NO) products and superoxide (O2(-)), compared to native C6 cells. In the present study, we examined the effects of pretreatment with some of free radical release inhibitors. The aim was to determine the origin of the enhanced generation of NO and superoxide, and to test the possibility of preventing it.

Stimulation of myelin proteolipid protein gene expression by eicosapentaenoic acid in C6 glioma cells.

In this study, the role of exogenous fatty acids in the regulation of proteolipid protein (PLP) gene expression was investigated using the following model culture system: C6 glioma cells expressing the green-fluorescent protein (eGFP) driven by different segments of PLP promoter. Eicosapentanoic acid (EPA; 20:5 n-3), but not arachidonic acid (AA; 20:4 n-6), induced a significant increase in medium fluorescence intensity (MFI) determined by fluorescence-activated cell sorting (FACS). The induction of PLP promoter was time-dependent showing maximal activity between 24 and 48 h after EPA exposure.

Free radical release in C6 glial cells enriched in hexacosanoic acid: implication for X-linked adrenoleukodystrophy pathogenesis.

Free radicals have been implicated in the etiopathology of some neurological and demyelinating diseases. To evaluate their involvement in the cerebral form of X-linked adrenoleukodystrophy (cerALD) disorder, characterised by very long chain fatty acid (VLCFA) accumulation, we utilised an in vitro model using rat C6 glial cells, enriched in hexacosenoic acid (C26:0, HA). Modified cells were incubated in presence of oxidative stressors, such as bacterial endotoxin lipopolisaccharides (LPS) and human oxidised low-density lipoprotein (ox-LDL), and the production of proinflammatory cytokines, nitrite, nitrate and superoxide was determined in the supernatants.

Dietary prenatal lipids affect myelin gene expression in postnatal undernourished rats.

The effects on myelin gene expression of prenatal diets with a different lipid content and fatty acid composition were investigated in undernourished pups. Three groups of rats were fed ad libitum during gestation diets containing either 10% of margarine or 10% of microbial lipids or a standard diet containing 3.5% of lipids.