Association of serum and hair antioxidant minerals with an oxidative stress marker in relation with characteristics of healthy adults: a cross-sectional study.

Excess oxidative stress generated in the body causes various types of cellular damage, including DNA damage. Certain trace minerals act as antioxidants by functioning as cofactors for antioxidant enzymes. This study was conducted to evaluate the serum and hair concentrations of major antioxidant trace minerals (zinc, manganese, selenium, and chromium) and to determine the association between the oxidative stress marker urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum or hair antioxidant trace mineral concentrations, according to the general characteristics of healthy adults. Study participants were selected after screening, and 108 participants aged 19-69 years were finally included. Serum and hair trace mineral concentrations were analyzed using inductively coupled plasma mass spectrometry, and urine 8-OHdG levels were quantified using an ELISA kit. Results showed that urinary 8-OHdG levels were significantly higher in exercisers than in those who did not exercise. Correlation analysis revealed that urinary 8-OHdG was negatively correlated with hair zinc in participants over 60 years of age and with poor health status, and positively correlated with hair chromium in participants with irregular dietary habits. In conclusion, these results suggest that urinary 8-OHdG is particularly correlated with hair zinc and chromium levels. Additional large-scale epidemiological studies are needed to generally confirm these findings.

Increased dietary vitamin D3 and calcium partially alleviate heat stress symptoms and inflammation in lactating Holstein cows independent of dietary concentrations of vitamin E and selenium.

Twelve multiparous Holstein cows (42.2 ± 5.6 kg of milk/d; 83 ± 27 d in milk) were used in a split-plot design testing the effects of mineral and vitamin supplementation on the time course of animal performance, metabolism, and inflammation markers during heat stress. The main plot was the average concentrations of dietary vitamin E and Se (adequate: 11.1 IU/kg of vitamin E and 0.55 mg/kg of Se, and high: 223 IU/kg of vitamin E and 1.8 mg/kg of Se, respectively). Within each plot, cows were randomly assigned to (1) heat stress (HS) with adequate concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D3 and Ca (HS+D3/Ca; 3,764 IU/kg and 0.97%, respectively), or (3) pair-feeding (PF) in thermoneutrality with adequate concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73% Ca) in a Latin square design with 14-d periods and 7-d washouts. The highest rectal temperature was recorded at 1700 h for HS (39.4°C; mean of d 1 to 14), being 1.2 and 0.8°C greater than for PF and HS+D3/Ca, respectively. Respiratory rate and water intake were higher in HS (73 breaths/min and 115 L/d, respectively) relative to PF (28 breaths/min and 76 L/d). Heat stress decreased dry matter intake progressively, reaching a nadir on d 5 to 7 (33% reduction) and was not different between treatments. Milk yield decreased progressively in all treatments, but remained greater in PF relative to HS from d 3 to 14 (10%), whereas HS and HS+D3/Ca were not different. Milk fat, protein, and lactose concentrations and yields were lower in HS relative to PF from d 3 to 14, but not different between HS and HS+D3/Ca. Relative to PF, preprandial insulin concentrations were increased in HS, whereas plasma nonesterified fatty acids were decreased on d 7 and 14. Plasma lipopolysaccharide-binding protein concentrations increased in HS cows on d 7 and 14, respectively, relative to PF, whereas they were reduced in HS + D3/Ca on d 14. Plasma C-reactive protein, tumor necrosis factor-α, and fecal calprotectin were increased in HS relative to both PF and HS+D3/Ca on d 7 and 14. Rectal temperature was positively associated with plasma lipopolysaccharide-binding protein (r = 0.72), tumor necrosis factor-α (r = 0.74), C-reactive protein (r = 0.87), and with milk somatic cells (r = 0.75). Plasma 8-hydroxy-2-deoxyguanosine concentrations presented a 3-way interaction, where 8-hydroxy-2-deoxyguanosine was lower in HS than in PF on d 7 and 14, and lower in HS+D3/Ca relative to HS on d 14 in the adequate vitamin E and Se treatment, but no effects were observed in the high vitamin E and Se group. Plasma superoxide dismutase concentrations increased over time, and were higher in HS relative to PF on d 14, whereas HS+D3/Ca was similar to HS. Heat stress markedly reduced milk production and milk components while increasing markers of leaky gut and inflammation. In contrast, vitamin D3 and Ca supplementation reduced hyperthermia (d 7-14), markers of leaky gut, and inflammation independent of dietary concentrations of vitamin E and Se.

Ameliorative effects of the phytochemicals in dates (Phoenix dactylifera) against the toxicological changes induced by fipronil in male albino rats.

Scientific evidence has shown that fipronil induces oxidative stress and genotoxicity. Our study aimed to evaluate the potential oxidation in redox parameters and DNA, as well as determine the protective effect of date extract of increasing resistance to cellular damage. 30 Male albino rats were divided into six groups ( n = 5): 1) control group; 2) treatment group with date extract (1 g/kg B.W.); 3) treatment group with 1/20 LD50 of fipronil; 4) treatment group with 1/40 LD50 of fipronil; 5) treatment group with 1/20 LD50 of fipronil + 1 g/kg date extract; and 6) treatment group with 1/40 LD50 of fipronil + 1 g/kg dates extract. Date extract showed a high content of phenolic compounds and antioxidant properties. Fipronil increased 8-hydroxy-2-deoxyguanosine levels and lipid peroxidation by malondialdehyde but decreased the total antioxidant capacity in plasma. Moreover, glutathione, catalase, and superoxide dismutase levels in the liver and kidney decreased, along with histopathological abnormalities. Additionally, tail moment parameters of liver DNA and micronucleus frequencies in the bone marrow increased. This study showed that fipronil-induced various health hazards in vivo, whereas date extract alleviated the said toxicological effects. However, date extract failed to reduce genotoxicity.

Relationship Between Zinc Status and DNA Oxidative Damage in Patients with Type 2 Diabetes Mellitus.

Although zinc deficiency increases the risk of oxidative DNA damage, data regarding the association between zinc and oxidative DNA damage in diabetes are controversial. In this article, we focus on serum zinc levels and its relation to an established biomarker of oxidative DNA damage (8-hydroxy-2-deoxyguanosine) in patients with type 2 diabetes, and to ascertain the beneficial effects of zinc supplementation on the level of oxidative DNA damage. The study consisted of 2 interrelated parts: The first part was a cross-sectional study conducted on patients with type 2 diabetes (n = 297) and healthy individuals (n = 188). The second part was an interventional study that enrolled 38 diabetic patients with low zinc status and high DNA damage. The demographic parameters including age, gender, and body mass index were recorded, and DNA damage marker through 8-hydroxy-2-deoxyguanosine levels, and zinc status of serum zinc, was measured. Significantly higher 8-hydroxy-2-deoxyguanosine levels (P < 0.00) together with lower zinc levels (P < 0.001) were found in the diabetics compared to healthy controls. Patients with low zinc status had higher levels of 8-hydroxy-2-deoxyguanosine compared to patients with normal zinc status. In diabetic patients, a negative correlation of 8-hydroxy-2-deoxyguanosine was observed with zinc (P = 0.070). Zinc supplementation showed a significant decrease in 8-hydroxy-2-deoxyguanosine by (26.0%) and increased in serum zinc by (42.0%). Elevated 8-hydroxy-2-deoxyguanosine levels in conjunction with low zinc status may indicate a high degree of oxidative DNA damage in diabetic patients. The results confirm that zinc supplementation in this group may help correct abnormal levels of 8-hydroxy-2-deoxyguanosine.

The effect of Hordeum vulgare on the monoaminergic system modulating neural-thyroid dysfunction in hypothyroid female rats.

Thyroid hormones regulate the development and maturation of the brain by maintaining levels of neurotransmitters and their related metabolites. The present work emphasizes the neural dysfunction in the brain caused by hypothyroidism and the potential role of Hordeum vulgare (water soluble barley, (B)) in ameliorating these effects. The study was conducted on euothyroid and hypothyroid adult female rats. The induction of hypothyroidism was conducted by oral-administration of neo-mercazole (5.0 mg.kg-1) daily for thirty days prior the study and terminated at the end of the study. The groups were assigned as; euthyroid (EU) and hypothyroid (H) groups and other two groups were treated with 100 mg.kg-1 water soluble barley; daily for one month and assigned as (EU+B) and (H+B) groups. Compared with EU and EU+B groups, a reduction in fT4, and ERK1/2 levels and elevation in TSH in brain tissue, Moreover, a  significant elevation in 8-OH deoxyguanosine and caspase-3 levels, confirmed with increase percentage DNA-damage in the brain and thyroid tissues in hypothyroid control rats. Furthermore, a significant decrease in all monoamines levels in different brain areas and downregulation of dopamine and 5-hydroxytreptamin receptors transcription, with a significant increase in excitatory amino acids and no significant change in the levels inhibitory amino acids were recorded in control hypothyroid group. Treatment of hypothyroid group with Hordeum vulgare improved the above-mentioned adverse impact by ameliorating the thyroid hormone levels with depleting the DNA-degradation and elaborating the levels of neurotransmitters with related receptors and amino acids in brain areas.  Water soluble Hordeum vulgare as a phytonutrient, is safe and efficient agent in ameliorating the neural dysfunction resulting from hypothyroidism status in adult female rats.

Guarana improves behavior and inflammatory alterations triggered by methylmercury exposure: an in vivo fruit fly and in vitro neural cells study.

Methylmercury (MeHg) is a well-known environmental pollutant associated with neurological and developmental deficits in animals and humans. However, epidemiological data showed that people living in the Amazon region although exposed to MeHg do not present these effects probably due to the protective effect of certain foods. We hypothesized here if guarana, a highly caffeinated fruit and consumed on a daily basis by Amazon people, could have some protective effect against MeHg toxicity using two complementary approaches. To assess locomotor impairment and sleep disruption, we used fruit fly (Drosophila melanogaster) model, and to evaluate neuroinflammation, we used human SH-SY5Y neural cells by measuring inflammatory cytokines levels. Results showed that guarana had a protective effect on the locomotor activity of male fruit flies reducing the excessive sleepiness caused by MeHg and increasing daily activity. Also, guarana increased the viability of flies and attenuated neural cells mortality. In addition, guarana reduced all pro-inflammatory cytokines levels increased by MeHg, along with caspase-1, caspase -3, caspase-8, and 8-dOHG levels, whereas increased the anti-inflammatory (IL-10) cytokine levels, which was decreased by MeHg. Our study provides new insights on the protective effects of guarana on the viability, locomotor activity, sleep, and activity patterns in vivo and the in vitro neuronal anti-inflammatory effect against MeHg toxicity.

Contribution of poly(ADP-ribose)polymerase-1 activation and apoptosis in trichloroethene-mediated autoimmunity.

Trichloroethene (TCE), a common environmental toxicant and widely used industrial solvent, has been implicated in the development of various autoimmune diseases (ADs). Although oxidative stress has been involved in TCE-mediated autoimmunity, the molecular mechanisms remain to be fully elucidated. These studies were, therefore, aimed to further explore the contribution of oxidative stress to TCE-mediated autoimmune response by specifically assessing the role of oxidative DNA damage, its repair enzyme poly(ADP-ribose)polymerase-1 (PARP-1) and apoptosis. To achieve this, groups of female MRL +/+ mice were treated with TCE, TCE plus N-acetylcysteine (NAC) or NAC alone (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day in drinking water) for 6 weeks. TCE treatment led to significantly higher levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the livers compared to controls, suggesting increased oxidative DNA damage. TCE-induced DNA damage was associated with significant activation of PARP-1 and increases in caspase-3, cleaved caspase-8 and -9, and alterations in Bcl-2 and Bax in the livers. Moreover, the TCE-mediated alterations corresponded with remarkable increases in the serum anti-ssDNA antibodies. Interestingly, NAC supplementation not only attenuated elevated 8-OHdG, PARP-1, caspase-3, cleaved caspase-9, and Bax, but also the TCE-mediated autoimmune response supported by significantly reduced serum anti-ssDNA antibodies. These results suggest that TCE-induced activation of PARP-1 followed by increased apoptosis presents a novel mechanism in TCE-associated autoimmune response and could potentially lead to development of targeted preventive and/or therapeutic strategies.

In-vitro evaluation of apoptotic effect of OEO and thymol in 2D and 3D cell cultures and the study of their interaction mode with DNA.

Oliveria decumbens is an Iranian endemic plant used extensively in traditional medicine. Recently, some studies have been performed on biological effects of Oliveria essential oil (OEO). However, to our knowledge, the anticancer activity of OEO has not been reported. Based on our GC/MS analysis, the basic ingredients of OEO are thymol, carvacrol, p-cymene and γ-terpinene. Therefore, we used OEO and its main component, thymol, to explore their effects on cell growth inhibition and anticancer activity. Despite having a limited effect on L929 normal cells, OEO/thymol induced cytotoxicity in MDA-MB231 breast cancer monolayers (2D) and to a lesser extent in MDA-MB231 spheroids (3D). Flow cytometry, caspase-3 activity assay in treated monolayers/spheroids and also fluorescence staining and DNA fragmentation in treated monolayers demonstrated apoptotic death mode. Indeed, OEO/thymol increased the Reactive Oxygen Species (ROS) level leading to mitochondrial membrane potential (MMP, ΔΨm) loss, caspase-3 activation and DNA damage caused S-phase cell cycle arrest. Furthermore, immunoblotting studies revealed the activation of intrinsic and maybe extrinsic apoptosis pathways by OEO/thymol. Additionally, in-vitro experiments, indicated that OEO/thymol interacts with DNA via minor grooves confirmed by docking method. Altogether, our reports underlined the potential of OEO to be considered as a new candidate for cancer therapy.

Effect of astragaloside IV on indoxyl sulfate-induced kidney injury in mice via attenuation of oxidative stress.

BACKGROUND: Astragalus membranaceus, a traditional Chinese medicine (TCM), has been widely used in the treatment of chronic kidney disease (CKD) in China. Astragaloside IV is one of the major compounds of Astragalus membranaceus. Recent research has shown that astragaloside IV demonstrates pharmacological effects, such as anti-inflammatory, anti-fibrotic and anti-oxidative stress activities. Our aim was to investigate the effects of astragaloside IV on indoxyl sulfate (IS)-induced kidney injury in vivo, and to study the underlying mechanism. METHODS: Forty C57BL/6 mice with ½ nephrectomy were divided into four groups: control group (n = 10), IS group (n = 10), IS plus 10 mg/kg of astragaloside IV group (n = 10) and IS plus 20 mg/kg of astragaloside IV group (n = 10). IS intraperitoneal injection and astragaloside IV treatment were administered continuously for 1 month. Next, the blood urea nitrogen (BUN) level, serum IS level, tubulointerstitial injury, renal oxidative stress and inflammatory injury were assessed. RESULTS: The IS intraperitoneal injection mouse group showed increasing levels of serum IS, BUN, tubulointerstitial injury, renal oxidative stress and inflammatory injury. Astragaloside IV treatment couldn't reduce the serum IS level or renal nuclear factor-κB and interleukin-1ß levels. However, 20 mg/kg astragaloside IV treatment reduced the BUN level and significantly attenuated IS-induced tubulointerstitial injury. Renal oxidative stress was decreased by the administration of astragaloside IV. CONCLUSIONS: These results suggest that astragaloside IV prevents IS-induced tubulointerstitial injury by ameliorating oxidative stress and may be a promising agent for the treatment of uremia toxin-induced injury.

Curcumin exerts a protective effect against premature ovarian failure in mice.

This study was designed to investigate the protective effect of curcumin against d-galactose (d-gal)-induced premature ovarian failure (POF) in mice. A mouse POF model was induced by subcutaneous injection of d-gal (200 mg/kg/day) daily for 42 days. Mice in the curcumin group received both d-gal treatment and intraperitoneal injection of curcumin (100 mg/kg/day) for 42 days. Ovarian function, oxidative stress and apoptosis were evaluated. The P, E2 and SOD levels were higher, and the FSH, LH and MDA levels were significantly lower in the curcumin group than those in the d-gal group. The proportion of primordial follicles was also significantly higher in the curcumin group than that in the d-gal group. In addition, curcumin treatment after d-gal administration resulted in significantly lower Sod2, Cat, 8-OhdG, 4-HNE, NTY and senescence-associated protein P16 expression levels, higher Amh expression levels and less apoptosis in granulosa cells than was observed in the d-gal group. Moreover, the p-Akt, Nrf2 and HO-1 protein expression levels were significantly higher and the apoptosis-related cleaved caspase-3 and -9 protein expression levels were markedly lower in the curcumin group than in the d-gal group. In conclusion, curcumin effectively inhibited d-gal-induced oxidative stress, apoptosis and ovarian injury via a mechanism involving the Nrf2/HO-1 and PI3K/Akt signaling pathways, suggesting that curcumin is a potential protective agent against POF.

Polyphenols protect against age-associated apoptosis in female rat cochleae.

Dietary antioxidants, polyphenols, have been found to be beneficial in protecting against the generation of oxidative stress in various diseases associated with aging. Age-related hearing loss (AHL) is the number one neurodegenerative disorder on our aged population. Sprague-Dawley rats divided into five groups according to their age (3, 6, 12, 18 and 24 months old) and treated with 100 mg/day/kg body weight of polyphenols were used. Then, cochleae were harvested to measure caspase activities (- 3, - 8 and - 9), caspase-3 gene expression, ATP levels, Bax, BcL-2 and p53 levels. 8-OHdG levels (marker of DNA oxidative damage) and annexin-V were also measured in cochleae. Increased levels of caspase-3 and 9 in cochlea were observed with age and this effect was attenuated by polyphenol treatment. In addition, ATP and Bcl-2 levels in older rats were recovered after administration of polyphenols, while Bax and p53 levels protein decreased. Oral supplementation with polyphenols also reduces DNA oxidative damage of cochlear cell. Treatment with polyphenols inhibits the activation of age-related apoptotic signaling by decreasing oxidative stress inside the rat cochlea.

Antioxidant activities of novel resveratrol analogs in breast cancer.

The objective of the present study was to characterize the role of novel resveratrol (Res) analogs: 4-(E)-{(4-hydroxyphenylimino)-methylbenzene, 1, 2-diol} (HPIMBD) and 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) as potent antioxidants against breast cancer. Non-neoplastic breast epithelial cell lines MCF-10A and MCF-10F were treated with 17ß-estradiol (E2), Res, HPIMBD, and TIMBD for up to 72 h. mRNA and protein levels of antioxidant genes, superoxide dismutase 3 (SOD3) and N-quinoneoxidoreductase-1 (NQO1) and transcription factors, nuclear factor erythroid 2-related factor (Nrf) 1, 2 and 3 were quantified after the above treatments. Generation of reactive oxygen species (ROS) was measured by CM-H2-DCFDA and oxidative-DNA damage was determined by measuring 8-hydroxy-2-deoxyguanosine (8-OHdG). HPIMBD and TIMBD scavenged cellular ROS production, attenuated oxidative DNA damage, increased mRNA and protein expression levels of SOD3 and NQO1 and activated Nrf signaling pathway. Our studies demonstrate that HPIMBD and TIMBD have the potential as novel antioxidants to prevent development of breast cancer.

Activation of the molecular and functional effects of Nrf2 against chronic iron oxide nanorod overload-induced cardiotoxicity.

Reactive oxygen species have a significant role in the pathogenesis of iron oxide nanorod (IONR) overload-induced organ toxicity in some organs such as the lungs. Green tea induces upregulation of phase II antioxidant enzymes that are transcriptionally organized by the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that when activated antagonize the oxidative stress induced by IONR overload that causes cardiotoxicity. The aim of the present study was to determine whether treatment of cardiotoxicity with iron chelators (deferiprone (DFP) or deferoxamine (DFO)) alone or in combination with phytochemical activation of Nrf2 (green tea) can protect cardiomyocytes from IONR overload-induced cardiotoxicity. One hundred five rats were distributed into seven groups: two control groups (non-IONR-overloaded and IONR-overloaded) and five IONR-overloaded groups such as a green tea group, DFP group, DFP combined with green tea group, DFO group, and DFO combined with green tea. Blood samples and cardiac tissues were obtained for estimation of total iron-binding capacity, ratio of myocardial 8-hydroxy-2'-deoxyguanosine/myocardial 2-deoxyguanosine, thiobarbituric acid reactive substances, glutathione (GSH) contents, and histopathological examination. The results showed mild histopathological changes in the heart and a significant decrease in all biochemical parameters, except for myocardial GSH, in the DFP group. The addition of green tea improved the biochemical and histopathological results compared with chelators alone.

4ß-Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells.

Reactive oxygen species (ROS) induction had been previously reported in 4ß-hydroxywithanolide (4ßHWE)-induced selective killing of oral cancer cells, but the mechanism involving ROS and the DNA damage effect remain unclear. This study explores the role of ROS and oxidative DNA damage of 4ßHWE in the selective killing of oral cancer cells. Changes in cell viability, morphology, ROS, DNA double strand break (DSB) signaling (γH2AX foci in immunofluorescence and DSB signaling in western blotting), and oxidative DNA damage (8-oxo-2'deoxyguanosine [8-oxodG]) were detected in 4ßHWE-treated oral cancer (Ca9-22) and/or normal (HGF-1) cells. 4ßHWE decreased cell viability, changed cell morphology and induced ROS generation in oral cancer cells rather than oral normal cells, which were recovered by a free radical scavenger N-acetylcysteine (NAC). For immunofluorescence, 4ßHWE also accumulated more of the DSB marker, γH2AX foci, in oral cancer cells than in oral normal cells. For western blotting, DSB signaling proteins such as γH2AX and MRN complex (MRE11, RAD50, and NBS1) were overexpressed in 4ßHWE-treated oral cancer cells in different concentrations and treatment time. In the formamidopyrimidine-DNA glycolyase (Fpg)-based comet assay and 8-oxodG-based flow cytometry, the 8-oxodG expressions were higher in 4ßHWE-treated oral cancer cells than in oral normal cells. All the 4ßHWE-induced DSB and oxidative DNA damage to oral cancer cells were recovered by NAC pretreatment. Taken together, the 4ßHWE selectively induced DSB and oxidative DNA damage for the ROS-mediated selective killing of oral cancer cells.

The biochemical effects of nano tamoxifen and some bioactive components in experimental breast cancer.

The effect of nano tamoxifen and some bioactive components such as yeast, isoflavone, and silymarin on the level of resistance and prevention of breast cancer progression in experimental animals is the target of this study. Thirty female Sprague-Dawley rats received a single medication dosage of 7,12-dimethylbenz[a]anthracene (DMBA) intragastrically. After fourteen days of DMBA admission, the procedure protocol started out. Finally, all the experimental results evaluated, tabulated and statistically analyzed. The results demonstrated a highly significant elevation in the 8-OHdG level in group 1 (nano yeast) and 3 (nano silymarin) while the results demonstrated a highly significant reduction in group 2 (nano tamoxifen). The apoptosis results demonstrated a significant elevation in group 3 (nano silymarin) where appeared significant reduction in group 4 (nano isoflavone). ErbB-2 results demonstrated a significant elevation in group 2 (nano tamoxifen) and a significant reduction in each of group 3 (nano silymarin) and 4 (nano isoflavone). The lipid peroxide level demonstrated an extremely significant reduction in group 4 (nano isoflavone). And a significant reduction of total antioxidant was observed in group 3 (nano silymarin) in comparison to injected animals control. This may be considered a new vision and strategy to resist breast cancer disease or prevent progression.

Argan oil reduces oxidative stress, genetic damage and emperipolesis in rats treated with acrylamide.

Acrylamide (AA), a well-known toxicant, is present in high-temperature-processed foods in heated foods. Argan oil (AO), a natural vegetable oil, is receiving increasing attention due to its powerful biological properties. However, limited information is available about its effects in lymphoid organs and bone marrow. The aim of this study is to investigate the effects of AO on hematological parameters, 8-hydroxydeoxyguanosine (8-OHdG), thiobarbituric acid reactive substances (TBARs), protein carbonyl (PCO), glutathione (GSH), myeloperoxidase (MPO) levels, the formation of micronucleus (MN) and megakaryocytic emperipolesis (ME) against AA-induced toxicity in rats. The animals were treated with AA (50mg/kg/day), AO (6ml/kg/day per day) and AA+AO (50mg+6ml/kg/day) for 30days. Treatment of rats with AA significantly decreased the hematological parameters, GSH and MPO activity and PCEs ratio while it increased TBARs, PCOs and 8-OHdG levels and formation of MN and ME. No significant differences were observed in the animals received the AO alone. Co-treatment with AA+AO ameliorated almost all of the alterations caused by AA and exhibited protective effect in rats. Based on the obtained results, we suggest that integration of AO in diet or using its supplements may be a good strategy for improving tissue injury in many diseases.

Topical application of ointment containing 0.5% green tea catechins suppresses tongue oxidative stress in 5-fluorouracil administered rats.

OBJECTIVE: The purpose of this study was to investigate the preventive effects of topical application of green tea catechins on tongue oxidative stress induced by 5-fluorouracil (5-FU) administration in rats. DESIGN: Male Wistar rats (n=28, 8 weeks old) were divided into four groups of seven rats each: a negative control group (saline administration and application of ointment without green tea catechins), a positive control group (5-FU administration and application of ointment without green tea catechins), and two experimental groups (5-FU administration and application of ointment containing 0.1% or 0.5% green tea catechins). Topical application of each ointment to the ventral surface of the tongue was performed once a day for 5days. The level of 8-hydroxydeoxyguanosine (8-OHdG) was determined to evaluate oxidative stress. Fluorescence staining was also performed to confirm nuclear factor erythroid 2-related factor 2 (Nrf2) translocation to the nucleus. RESULTS: After the experimental period, the ratios of 8-OHdG-positive cells in the ventral tongue tissue were higher in the positive control group than in the negative control group (P<0.05). On the other hand, those in the 0.5% green tea catechin group, but not in the 0.1% green tea catechin group, were lower than the positive control group (P<0.05). In addition, Nrf2 translocation to the nucleus was greater in the 0.5% green tea catechin group than in the positive control group (P<0.05). CONCLUSIONS: Topical application of ointment containing 0.5% green tea catechins could prevent tongue oxidative stress in 5-FU administered rats, via up-regulation of the Nrf2 signaling pathway.

Hepatoprotective mechanism of Lygodium microphyllum (Cav.) R.Br. through ultrastructural signaling prevention against carbon tetrachloride (CCl4)-mediated oxidative stress.

Plants have been consumed in medicinal practices for centuries. Lygodium microphyllum (Cav.) R.Br. (Lygodiaceae), also known as Old World Climbing Fern, is a medicinal plant used by local communities in Sabah for skin and dysentery ailments. This study aims to test aqueous extract of L. microphyllum leaves for hepatoprotective and immunosuppressive activity in rats. Animal studies were carried out to evaluate hepatoprotection of aqueous extract of L. microphyllum at different doses (200, 400 and 600mg/kg b.w.) against carbon tetrachloride (CCl4)-mediated liver injury and histopathological alterations. Total phenolic content in aqueous extract of L. microphyllum leaves was 206.38±9.62mg gallic acid equivalent/g. The inhibitory concentration (IC50) for free radical scavenging activity of L. microphyllum was reached at a concentration of 65µg/ml.L. microphyllum was able to prevent the increase in levels of serum alanine aminotransferase, serum aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal, 8-hydroxydeoxyguanosine) and pro-inflammatory cytokines (Tumor Necrosis Factor-α, Interleukin-6, Prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations showed protective effects by L. microphyllum against CCl4-mediated oxidative stress. Hepatoprotective mechanism of L. microphyllum can be attributed to its antioxidative effects through protection of ultrastructural organelles.

Attenuation of acute lung injury in a rat model by Semen Cassiae.

BACKGROUND: Acute lung injury (ALI) is an inflammatory disorder. Semen Cassiae has potent anti-inflammatory activities. The aim of our study was to investigate whether Semen Cassiae plays a protective effect on lipopolysaccharide (LPS)-induced ALI and, if so, to elucidate its potential mechanism. METHODS: Male Sprague-Dawley rat lungs were injured by intratracheal instillation of LPS. Rats were treated with Semen Cassiae or vehicle 3 h after LPS challenge. Samples were harvested 24 h post-LPS administration. We also investigated the effects of Semen Cassiae on LPS stimulation in RAW 264.7 cells. RESULTS: LPS administration markedly induced pulmonary edema and polymorphonuclear neutrophil influxes. These changes were significantly attenuated in Semen Cassiae treated group. Moreover, Semen Cassiae markedly reduced pulmonary interleukin (IL)-6, tumor necrosis factor (TNF)-α, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. The pulmonary soluble epoxide hydrolase (sEH) activity and the DNA binding activity of Nuclear factor (NF)-κB were significantly inhibited in Semen Cassiae treated group. Furthermore, Semen Cassiae treatment significantly increased epoxyeicosatrienoic acids (EETs), and heme oxygenase-1 (HO-1) activity. Our in vitro study demonstrates that Semen Cassiae treatment may inhibit LPS induced IκBα phosphorylation and NF-κB p65 nucleus translocation. CONCLUSION: Semen Cassiae protects LPS-induced ALI in rats. Semen Cassiae can be developed as a novel treatment for ALI.

Nature of fly ash amendments differently influences oxidative stress alleviation in four forest tree species and metal trace element phytostabilization in aged contaminated soil: A long-term field experiment.

Aided phytostabilization using coal fly ashes (CFAs) is an interesting technique to clean-up polluted soils and valorizing industrial wastes. In this context, our work aims to study the effect of two CFAs: silico-aluminous (CFA1) and sulfo-calcic (CFA2) ones, 10 years after their addition, on the phytostabilization of a highly Cd (cadmium), Pb (lead) and Zn (zinc) contaminated agricultural soil, with four forest tree species: Robinia pseudoacacia, Alnus glutinosa, Acer pseudoplatanus and Salix alba. To assess the effect of CFAs on trees, leaf fatty acid composition, malondialdehyde (MDA), oxidized and reduced glutathione contents ratio (GSSG: GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), Peroxidase (PO) and Superoxide dismutase (SOD) activities were examined. Our results showed that CFA amendments decreased the CaCl2-extractable fraction of Cd and Zn from the soil. However, no significant effect was observed on metal trace element (MTE) concentrations in leaves. Fatty acid percentages were only affected by the addition of sulfo-calcic CFA. The most affected species were A. glutinosa and R. pseudoacacia in which C16:0, C18:0 and C18:2 percentages increased significantly whereas the C18:3 decreased. The addition of sulfo-calcic CFA induced the antioxidant systems response in tree leaves. An increase of SOD and POD activities in leaves of trees planted on the CFA2-amended plot was recorded. Conversely, silico-aluminous CFA generated a reduction of lipid and DNA oxidation associated with the absence or low induction of anti-oxidative processes. Our study evidenced oxidative stress alleviation in tree leaves due to CFA amendments. MTE mobility in contaminated soil and their accumulation in leaves differed with the nature of CFA amendments and the selected tree species.