Early-Life Exposure to Commercial Formulation Containing Deltamethrin and Cypermethrin Insecticides Impacts Redox System and Induces Unexpected Regional Effects in Rat Offspring Brain.

Several studies have shown that the oxidative impact of pesticides is most prevalent in rural environments where they are intensively used. At different levels, pyrethroids are reported to promote neurodegeneration; they share the ability to promote oxidative stress, and to induce mitochondrial impairments, α-synuclein overexpression and neuronal cell loss. The present study evaluates the impact of early-life exposure to a commercial formulation containing deltamethrin (DM) and cypermethrin (CYP) at a dose of 1/100 LD50 (1.28 and 2.5 mg/kg, respectively). Rats aged 30 days old, treated from the 6th to the 21st day of life, were tested for brain antioxidant activity and α-synuclein levels. Four regions of the brain were analyzed: the striatum, cerebellum, cortex and hippocampus. Our data demonstrated a significant increase in catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) antioxidant levels in the brain regions compared to the controls. Pups exhibited no significant changes in protein carbonyl levels and lipid peroxidation. Striatal α-synuclein expression was significantly reduced in the rats exposed to DM + CYP, while the treatment resulted in a non-significant increase in the other brain areas. These findings indicate unexpected effects of postnatal treatment with the commercial formulation containing DM and CYP on brain redox state and α-synuclein expression, suggesting an adaptive response.

Gender-Related Differences in Trimethylamine and Oxidative Blood Biomarkers in Cardiovascular Disease Patients.

Gender differences in the burden of cardiovascular disease (CVD) have been observed worldwide. In this study, plasmatic levels of trimethylamine (TMA) and blood oxidative biomarkers have been evaluated in 358 men (89 controls and 269 CVD patients) and 189 women (64 control and 125 CVD patients). The fluorescence technique was applied to determine erythrocyte membrane fluidity using 1,6-diphenyl-1,3,5-hexatriene (DPH) and Laurdan, while lipid hydroperoxides were assessed by diphenyl-1-pyrenylphosphine (DPPP). Results show that levels of plasmatic TMA were higher in healthy men with respect to healthy women (p = 0.0001). Significantly lower TMA was observed in male CVD patients (0.609 ± 0.104 µM) compared to healthy male controls (0.680 ± 0.118 µM) (p < 0.001), while higher levels of TMA were measured in female CVD patients (0.595 ± 0.115 µM) with respect to female controls (0.529 ± 0.073 µM) (p < 0.001). DPPP was significantly higher in healthy control men than in women (p < 0.001). Male CVD patients displayed a lower value of DPPP (2777 ± 1924) compared to healthy controls (5528 ± 2222) (p < 0.001), while no significant changes were measured in females with or without CVD (p > 0.05). Membrane fluidity was significantly higher (p < 0.001) in the hydrophobic bilayer only in control male subjects. In conclusion, gender differences were observed in blood oxidative biomarkers, and DPPP value might be suggested as a biomarker predictive of CVD only in men.

Chemical and Sensory Profiling of Monovarietal Extra Virgin Olive Oils from the Italian Marche Region.

Chemical and sensory peculiarities of monovarietal extra virgin olive oils (MEVOOs) from the cultivars (cvs.) Ascolana tenera (ASC), Coroncina (COR), Mignola (MIG), Piantone di Mogliano (MOG), and Raggia (RAG) from Marche region (Italy) are investigated. Their polar phenolic substances and α-tocopherol are analysed through high performance liquid chromatography with different detectors. Volatile substances, fatty acid composition, and squalene are analysed by gas chromatography coupled to mass spectrometry (MS) and to the flame ionization detector, respectively. Total antioxidant activity and sensory analysis were also performed. MOG showed high squalene content (on average 0.88 ± 0.16 g/100 g), high relative amount of α-copaene among volatiles, and the highest oleic acid percentage. MIG had high α-tocopherol content (on average 350.0 ± 57.6 mg kg-1) and high α-farnesene in the volatile fraction. ASC showed the highest sensory quality and the lignan pinoresinol with higher concentration as compared to the other MEVOOs (p < 0.05), which resulted in a possible chemical marker for this cv. RAG was characterized by the sensory note of almond, which corresponds to its highest (E)-2-hexenal percentage. Sensory analysis and an antioxidant activity assay performed on a set of industrial extra virgin olive oils purchased in supermarkets, highlighted MEVOOs' superiority from these points of view. Principal component analysis displays the main characteristics of the cvs. investigated.

Extra Virgin Olive Oil and Nigella sativa Oil Produced in Central Italy: A Comparison of the Nutrigenomic Effects of Two Mediterranean Oils in a Low-Grade Inflammation Model.

Extra virgin olive (EVO) oil and Nigella sativa (NG) oil are two well-known Mediterranean foods whose consumption has been associated with beneficial effects on human health. This study investigates the nutrigenomic properties of two high quality EVO and NG oils in an in vitro model of low-grade inflammation of human macrophages (THP-1 cells). The aim was to assess whether these healthy foods could modulate inflammation through antioxidant and epigenetic mechanisms. When THP-1 cells were co-exposed to both lipopolysaccharides (LPS)-induced inflammation and oils, both EVO and NG oils displayed anti-inflammatory activity. Both oils were able to restore normal expression levels of DNMT3A and HDAC1 (but not DNMT3B), which were altered under inflammatory conditions. Moreover, EVO oil was able to prevent the increase in TET2 expression and reduce global DNA methylation that were measured in inflamed cells. Due to its antioxidant properties, EVO oil was particularly efficient in restoring normal levels of membrane fluidity, which, on the contrary, were reduced in the presence of inflammation. In conclusion, these data support the hypothesis that these Mediterranean oils could play a major role in the modulation of low-grade inflammation and metabolic syndrome prevention. However, NS oil seems to be more efficient in the control of proinflammatory cytokines, whereas EVO oil better helps to counteract redox imbalance. Further studies that elucidate the nutrigenomic properties of local produce might help to promote regional the production and consumption of high-quality food, which could also help the population to maintain and promote health.

Positive effect of an electrolyzed reduced water on gut permeability, fecal microbiota and liver in an animal model of Parkinson's disease.

There is growing awareness within the scientific community of the strong connection between the inflammation in the intestine and the pathogenesis of Parkinson's disease (PD). In previous studies we developed a PD animal model exposing pup rats to permethrin (PERM) pesticide. Here, we intended to explore whether in our animal model there were changes in gut permeability, fecal microbiota and hepatic injury. Moreover, we tested if the co-treatment with an electrolyzed reduced (ERW) was effective to protect against alterations induced by PERM. Rats (from postnatal day 6 to 21) were gavaged daily with PERM, PERM+ERW or vehicle and gut, liver and feces were analyzed in 2-months-old rats. Increased gut permeability, measured by FITC-dextran assay, was detected in PERM group compared to control and PERM+ERW groups. In duodenum and ileum, concentration of occludin was higher in control group than those measured in PERM group, whereas only in duodenum ZO-1 was higher in control than those measured in PERM and PERM+ERW groups. Number of inflammatory focis and neutrophils as well as iNOS protein levels were higher in livers of PERM-treated rats than in those of PERM+ERW and control rats. Fecal microbiota analysis revealed that Lachnospira was less abundant and Defluviitaleaceae more abundant in the PERM group, whereas the co-treatment with ERW was protective against PERM treatment since the abundances in Lachnospira and Defluviitaleaceae were similar to those in the control group. Higher abundances of butyrate- producing bacteria such as Blautia, U.m. of Lachnospiraceae family, U.m. of Ruminococcaceae family, Papillibacter, Roseburia, Intestinimonas, Shuttleworthia together with higher butyric acid levels were detected in PERM+ERW group compared to the other groups. In conclusion, the PD animal model showed increased intestinal permeability together with hepatic inflammation correlated with altered gut microbiota. The positive effects of ERW co-treatment observed in gut, liver and brain of rats were linked to changes on gut microbiota.

Anti-Inflammatory, Anti-Arthritic and Anti-Nociceptive Activities of Nigella sativa Oil in a Rat Model of Arthritis.

This study investigated the preventive efficacy of the crude oil extracted from Nigella sativa seeds in a rat model of arthritis induced by using complete Freund's adjuvant (CFA). Nigella sativa oil at 1.82 mL/kg or 0.91 mL/kg (corresponding to 1596 and 798 mg/kg, respectively) was orally administered for 25 days from the day of immunization. One immunized group was treated orally with indomethacin (3 mg/kg) as a reference drug. Body weight growth rate, paw swelling, arthritis score, mechanical allodynia, locomotor activity and anxiety-like behavior were observed, and the levels of Interleukin 6 (IL-6), C-reactive protein, albumin and total cholesterol in plasma were measured on days 15 and 25. Nigella sativa oil showed anti-inflammatory, anti-arthritic and anti-nociceptive activities that were significant as compared to untreated arthritic rats but less than indomethacin. These results indicated that Nigella sativa oil significantly attenuated adjuvant-arthritis in rats and the higher dose (1.82 mL/kg) prevented the development of arthritis with an inhibition of 56%.

Early impairment of epigenetic pattern in neurodegeneration: Additional mechanisms behind pyrethroid toxicity.

Permethrin is a synthetic pyrethroid extensively used as anti-woodworm agent and for indoor and outdoor pest control. The main route of human exposure is through fruit, vegetable and milk intake. Low dosage exposure to permethrin during neonatal brain development (from postnatal day 6 to postnatal day 21) leads to dopamine decrease in rat striatum nucleus, oxidative stress and behavioural changes linked to the development of Parkinson's like neurodegeneration later in life. The aim of this study was to evaluate the expression of genes involved in the dopaminergic pathway and epigenetic regulatory mechanisms in adolescent rats treated with permethrin during neonatal brain development. Furthermore, in order to shed light on the mechanisms associated with molecular impairments, in silico studies were performed. The outcomes show increased expression of genes related to the dopamine-synthesis pathway (Nurr1, Th, Snca), epigenetics (TET proteins and Mecp2) and exposure to toxicants (Pon1 and Pon2) in adolescent rats compared with control group. Furthermore, increased global 5mC and 5hmC levels were observed in the DNA extracted from striatum of early-life treated rats in comparison with controls. FAIRE-qPCR analysis shows that permethrin induces an enrichment of chromatin-free DNA at the level of Th and Nurr1 promoters, and ChIP-qPCR reveals a significant reduction in methylation levels at H3K9me3 position at both Th and Nurr1 promoter regions. In silico studies show that permethrin competes for the same two binding sites of known NURR1 agonists, with a lower binding free energy for permethrin, suggesting an important durable association of permethrin with the orphan receptor. Moreover, alpha-synuclein shows a strong affinity for NURR1, corroborating previous experimental outcomes on the interactions between them. This study focuses on an emerging role of early-life exposure to environmental pollutants in the regulation of late onset diseases through intriguing mechanisms that change crucial epigenetic patterns starting from adolescent age.

Antioxidant and Anti-Inflammatory Properties of Nigella sativa Oil in Human Pre-Adipocytes.

The oil obtained from the seeds of Nigella sativa L. (N. sativa), also known as black cumin, is frequently used in the Mediterranean area for its anti-inflammatory, anti-oxidant, and anti-cancer activities. The aim of the present study was to evaluate the antioxidant and anti-inflammatory properties of the oil extracted from seeds of a N. sativa cultivar produced in the Marche region of Italy, and to determine if the thymoquinone content, antioxidant properties, and biological activity would decay during storage. Cytotoxicity and anti-inflammatory properties of N. sativa oil were tested in an in vitro model of low-grade inflammation in Simpson⁻Golabi⁻Behmel syndrome human pre-adipocytes. The fresh extracted oil (FEO) contained 33% more thymoquinone than stored extracted oil (SEO), demonstrating that storage affects its overall quality. In addition, the thymoquinone content in the N. sativa oil from the Marche region cultivar was higher compared with other N. sativa oils produced in the Middle East and in other Mediterranean regions. Pro-inflammatory cytokines (e.g., Interleukin (IL)-1alpha, IL-1beta, IL-6) were differently modulated by fresh and stored extracts from N. sativa oils: FEO, containing more thymoquinone reduced IL-6 levels significantly, while SEO inhibited IL-1beta and had a higher antioxidant activity. Total antioxidant activity, reported as µM of Trolox, was 11.273 ± 0.935 and 6.103 ± 0.446 for SEO and FEO (p = 1.255 × 10-7), respectively, while mean values of 9.895 ± 0.817 (SEO) and 4.727 ± 0.324 (FEO) were obtained with the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay (p = 2.891 × 10-14). In conclusion, the oil capacity to counteract proinflammatory cytokine production does not strictly depend on the thymoquinone content, but also on other antioxidant components of the oil.

Chemical and sensory differences between high price and low price extra virgin olive oils.

The aim of the study was to identify new potential chemical markers of extra virgin olive oil (EVOO) quality by using a multicomponent analysis approach. Sixty-six EVOOs were purchased from the Italian market and classified according to their price as low price EVOOs (LEVOOs) and high price EVOOs (HEVOOs) costing 3.60-5.90euro/L and 7.49-29.80euro/L respectively. Sensory and chemical parameters strictly related to olive oil quality have been investigated, like volatile substances, polar phenolic substances, antioxidant activity, fatty acid composition, and α-tocopherol. Significant differences in terms of chemical composition and sensory features have been highlighted between the two EVOOs classes investigated, proving a generally lower level of quality of LEVOOs, clearly showed also by means of principal component analysis. Among the most interesting outcomes, R ratio (free tyrosol and hydroxytyrosol over total free and bound forms), measuring the extent of secoiridoids hydrolysis, resulted to be significantly higher in LEVOOs than in HEVOOs. Other key differences were found in the volatile substances composition, in the stearic acid percentage and in p-coumaric acid content.

HTR2C Gene Variant and Salivary Cortisol Levels after Endurance Physical Activity: A Pilot Study.

INTRODUCTION: The 5-hydroxytryptamine 2C receptor (HTR2C) rs6318 polymorphism has been associated with increased sensitivity to stress. This study investigated whether the rs6318 genotype modified the cortisol response to endurance physical activity. METHODS: The HTR2C SNP was genotyped in a population of agonistic cyclists, and salivary cortisol levels were measured before and after an endurance competition. RESULTS AND CONCLUSION: Salivary cortisol levels increased after the competition (from 20.72 ± 12.36 ng/mL to 33.80 ± 21.53 ng/mL; p = 3.189 × 10-5). rs6318 C carriers displayed higher baseline cortisol levels compared to G carriers (26.60 ± 9.35 ng/mL vs. 19.50 ± 12.63 ng/mL; p = 0.04). Baseline cortisol levels were able to predict the cortisol response to exercise (ß = -0.846; p = 1.2 × 10-5). Although regression analysis did not identify an association between HTR2C genotype and change in cortisol levels, a secondary analysis in which the population was classified by median cortisol changes suggested that they might be weakly associated, thus warranting further investigation.

Permethrin pesticide induces NURR1 up-regulation in dopaminergic cell line: Is the pro-oxidant effect involved in toxicant-neuronal damage?

The mechanisms associated to the development of neurodegeneration due to pesticide exposure are not clear yet. In this study we evaluated how permethrin pesticide (PERM) can influence the Nurr1 gene and protein expression, and if a pro-oxidant activity of the pesticide contributes to up-regulation of Nurr1 in a dopaminergic cell line. Incubation of PC12 cells with 1µM PERM for 72h, leads to over expression of Nurr1 gene. This effect occurs with both corn oil and extra virgin olive oil (EVO) used to solubilize the toxicant. In order to investigate if the Nurr1 up-regulation induced by PERM, was associated to the pro-oxidant activity of the pesticide, anti-oxidants as glutathione (GSH), tocotrienols (TOC) and Electrolyzed Reduced Water (ERW) were tested. RT-PCR of Nurr1 showed that its up-regulation was significantly reduced in the presence of antioxidants, especially by addition of ERW. Western-blot analysis reveals that ERW was able to counterbalance the up-regulation of Nurr1 protein induced by permethrin exposure.

In vivo and in silico studies to identify mechanisms associated with Nurr1 modulation following early life exposure to permethrin in rats.

The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat's life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated α-synuclein protein levels. Adult rats showed enhanced DNMT3b and α-synuclein aggregation compared to the control group, while with aging a significant decrease in all biomarkers studied was observed. No changes in Nurr1 promoter methylation in adolescent, adult and old rats were found. In silico studies showed clear evidence of a strong binding interaction between PERM and its metabolite 3-phenoxybenzoic acid with the nuclear orphan receptor Nurr1. These findings suggest that an additional interference with the dopaminergic neuron pathway could occur in situ during PERM accumulation in brain. Therefore, Nurr1 modulation in early life PERM-treated rats, depends on age-related adaptive responses in animals.

Changes on fecal microbiota in rats exposed to permethrin during postnatal development.

Alteration of the gut microbiota through diet and environmental contaminants may disturb the mammalian digestive system, leading to various diseases. Because most exposure to environmentally pyrethroid pesticides such as permethrin (PERM) occurs through the diet, the commensal gut microbiota is likely to be exposed to PERM. The study aimed at evaluating the effect of low-dose exposure to PERM in early life on the composition of fecal microbiota in rats. Over a 4-month follow-up period, fecal microbiota and short-chain fatty acids were measured in order to identify possible differences between PERM-treated rats and controls. Further in vitro antimicrobial experiments were conducted to establish the antibacterial activity of PERM against different strains to obtain Minimal Inhibitory Concentrations. The main finding focused on the reduced abundance of Bacteroides-Prevotella-Porphyromonas species, increased Enterobacteriaceae and Lactobacillus in PERM-treated rats compared to controls. Changes of acetic and propionic acid levels were registered in PERM-treated group. From in vitro studies, PERM showed higher antibacterial activity against beneficial bacteria such as Bifidobacterium and Lactobacillus paracasei, while to inhibit potential pathogens as Staphylococcus aureus and Escherichia coli PERM concentration needed to be increased. In summary, exposure to PERM could affect the fecal microbiota and could be a crucial factor contributing to the development of diseases.

Proteomic analysis for early neurodegenerative biomarker detection in an animal model.

The exposure to xenobiotics in the early stages of life represents the most important component in the etiology of many neurodegenerative disorders. Proteomic analysis of plasma and brain samples from early life treated animal model was performed in order to identify early biomarkers of neurodegeneration. Two-dimensional gel electrophoresis followed by liquid chromatography-tandem mass spectrometry identified four proteins in the plasma of adolescent rats that deviated from the control group. Low expression levels of transthyretin and plasma transferrin, and the absence of long-chain fatty acid transport 1 were measured. On the other hand, the same proteomic approach was done on striatum of an adult rat model of neurodegeneration. Mitochondrial aspartate aminotransferase and voltage-dependent anion channel were under expressed, while mitochondrial malate dehydrogenase, myelin basic protein and ubiquitin-60S ribosomal protein L40 were absent in striatum of animal model compared to control group. Data show that early biomarkers for the diagnosis of neurodegeneration can be obtained by proteomic analysis, starting from adolescent age and the results highlight the time frame for the onset of neurodegeneration due to early exposure to xenobiotics.

Antioxidant and anti-inflammatory activities of extracts from Cassia alata, Eleusine indica, Eremomastax speciosa, Carica papaya and Polyscias fulva medicinal plants collected in Cameroon.

BACKGROUND: The vast majority of the population around the world has always used medicinal plants as first source of health care to fight infectious and non infectious diseases. Most of these medicinal plants may have scientific evidence to be considered in general practice. OBJECTIVE: The aim of this work was to investigate the antioxidant capacities and anti-inflammatory activities of ethanol extracts of leaves of Cassia alata, Eleusine indica, Carica papaya, Eremomastax speciosa and the stem bark of Polyscias fulva, collected in Cameroon. METHODS: Chemiluminescence was used to analyze the antioxidant activities of plant extracts against hydrogen peroxide or superoxide anion. Comet assays were used to analyze the protection against antioxidant-induced DNA damage induced in white blood cells after treating with hydrogen peroxide. Flow cytometry was used to measure γδ T cells proliferation and anti-inflammatory activity of γδ T cells and of immature dendritic cells (imDC) in the presence of different concentrations of plant extracts. RESULTS: Ethanol extracts showed strong antioxidant properties against both hydrogen peroxide and superoxide anion. Cassia alata showed the highest antioxidant activity. The effect of plant extracts on γδ T cells and imDC was evidenced by the dose dependent reduction in TNF-α production in the presence of Cassia alata, Carica papaya, Eremomastax speciosa Eleusine indica, and Polyscias fulva. γδ T cells proliferation was affected to the greatest extent by Polyscias fulva. CONCLUSION: These results clearly show the antioxidant capacity and anti-inflammatory activities of plant extracts collected in Cameroon. These properties of leaves and stem bark extracts may contribute to the value for these plants in traditional medicine and in general medical practice.

Effect of 17ß-estradiol on striatal dopaminergic transmission induced by permethrin in early childhood rats.

A positive effect of estrogen treatment has been observed in neurodegenerative diseases such as Parkinson's disease. Since 17ß-estradiol can modulate positively dopaminergic system, here we sought to evaluate the effect of 17ß-estradiol supplementation on an animal model developing dopaminergic alterations on nucleus of striatum after neonatal exposure to permethrin pesticide. The goal of the study was to verify if the co-treatment with 17ß-estradiol could protect against the damage induced by pesticide exposure in early life. Permethrin treated rats showed a decrease of dopamine and Nurr1 gene expression in striatum, while a more pronounced decrease of dopamine was observed in rats co-administered with permethrin+17ß-estradiol. No difference between control and permethrin treated rats was observed in both mRNA of ERα and ERß, whereas the rats co-administered with permethrin+17ß-estradiol showed a down-regulation of ERα expression. The in vitro studies showed that permethrin, at high concentration may have an antagonist effect on ERα and even more pronounced in ERß, thus suggesting that permethrin may block the estrogen neuroprotective effects. In conclusion, in male rats, the administration of estrogen further enhanced the impairment of dopaminergic transmission due to exposure to permethrin.

Neonatal exposure to permethrin pesticide causes lifelong fear and spatial learning deficits and alters hippocampal morphology of synapses.

BACKGROUND: During the neurodevelopmental period, the brain is potentially more susceptible to environmental exposure to pollutants. The aim was to determine if neonatal exposure to permethrin (PERM) pesticide, at a low dosage that does not produce signs of obvious abnormalities, could represent a risk for the onset of diseases later in the life. METHODS: Neonatal rats (from postnatal day 6 to 21) were treated daily by gavage with a dose of PERM (34 mg/kg) close to the no-observed-adverse-effect level (NOAEL), and hippocampal morphology and function of synapses were investigated in adulthood. Fear conditioning, passive avoidance and Morris water maze tests were used to assess cognitive skills in rats, whereas electron microscopy analysis was used to investigate hippocampal morphological changes that occurred in adults. RESULTS: In both contextual and tone fear conditioning tests, PERM-treated rats showed a decreased freezing. In the passive avoidance test, the consolidation of the inhibitory avoidance was time-limited: the memory was not impaired for the first 24 h, whereas the information was not retained 72 h following training. The same trend was observed in the spatial reference memories acquired by Morris water maze. In PERM-treated rats, electron microscopy analysis revealed a decrease of synapses and surface densities in the stratum moleculare of CA1, in the inner molecular layer of the dentate gyrus and in the mossy fibers of the hippocampal areas together with a decrease of perforated synapses in the stratum moleculare of CA1 and in the inner molecular layer of the dentate gyrus. CONCLUSIONS: Early-life permethrin exposure imparts long-lasting consequences on the hippocampus such as impairment of long-term memory storage and synaptic morphology.

The effect of ethyl pyruvate supplementation on rat fatty liver induced by a high-fat diet.

Continuous positive energy imbalance leads to obesity, which increases the risk of developing non-alcoholic fatty liver disease. The hepatoprotective effect of ethyl pyruvate has been revealed in several studies. Therefore, we examined the effect of ethyl pyruvate supplementation on liver cell damage, metabolism, membrane fluidity, and oxidative stress markers in rats fed a high-fat diet. After 6-wk feeding of a control or high-fat diet, Wistar rats were divided into 4 groups: control diet, control diet and ethyl pyruvate, high-fat diet, and high-fat diet and ethyl pyruvate. Ethyl pyruvate was administered as a 0.3% solution in drinking water, for the following 6 wk. Ethyl pyruvate intake attenuated the increase in activities of plasma transaminases and liver TNF-α. However, the supplementation was without effect in the lipid profiles, membrane fluidity or oxidative metabolism in liver induced by the high-fat diet. Our data confirm the potency of ethyl pyruvate against cell liver damage. Nevertheless, prolonged intake did not affect the development of a fatty liver.

Exercise-induced heart mitochondrial cholesterol depletion influences the inhibition of mitochondrial swelling.

The significance of the reduction of the cholesterol pool in heart mitochondria after exercise is still unknown. Recently, published data have suggested that cholesterol may influence the components of mitochondrial contact site and affect mitochondrial swelling. Therefore, the aim of this study was to determine whether the decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and result in an increased resistance to calcium chloride-induced mitochondrial swelling. Male Wistar rats were divided into a sedentary control group and an exercise group. The rats exercised for 3 h, burdened with an additional 3% of their body weight. Their hearts were removed immediately after completing the exercise. The left ventricle was divided and used for experiments. Mitochondrial cholesterol content, membrane fluidity and mitochondrial bioenergetics were measured in the control and exercised rat heart mitochondria. To assess whether mitochondrial modifications are linked to disruption of lipid microdomains, methyl-ß-cyclodextrin, a well-known lipid microdomain-disrupting agent and cholesterol chelator, was applied to the mitochondria of the control group. Cholesterol depletion, increased membrane fluidity and increased resistance to calcium chloride-induced swelling were observed in postexercise heart crude mitochondrial fraction. Similar results were achieved in control mitochondria treated with 2% methyl-ß-cyclodextrin. All of the mitochondrial bioenergetics parameters were similar between the groups. Therefore, the disruption of raft-like microdomains appears to be an adaptive change in the rat heart following exercise.

Imbalance in redox system of rat liver following permethrin treatment in adolescence and neonatal age.

The effect of different permethrin treatments on the redox system of rat liver, is presented. Two types of oral administration were chosen: (i) sub-chronic treatment (1/10 of LD50 for 60 days) during adolescence (5 weeks old) and (ii) sub-acute treatment (1/44 of LD50 for 15 days) during early life (from postnatal days 6-21). The results show that adolescent permethrin treatment induces damage to the liver redox system, increasing lipid and protein peroxidation and reducing membrane fluidity in the hydrophilic--hydrophobic region of the bilayer. In addition, glutathione peroxidase (GPx) and GSH levels resulted decreased, while glutathione transferase (GST) and catalase (CAT) levels increased. The rats treated in early life with permethrin and sacrificed in adult age, showed less signs of damage compared to those exposed during adolescence in which lipid peroxidation was increased by 32%, whereas for the first group the raise was only 11%. Moreover, fluidity improved in the deeper hydrophobic membrane region of the treated group, while the level of CAT was significantly lower compared to the control one. Although sub-chronic treatment increased CAT and GST and decreased GPx and GSH levels, the present data suggest that a shorter exposure to permethrin during neonatal age decreased CAT level and it could represent an important risk factor for the onset of long-term liver damage.