Exogenous melatonin protects preimplantation embryo development from decabromodiphenyl ethane-induced circadian rhythm disorder and endogenous melatonin reduction.

Decabromodiphenyl ethane (DBDPE) is a novel flame retardant that is widely used in plastics, electronic products, building materials and textiles. Our previous studies have revealed the oocyte toxicity of DBDPE, but the effect of DBDPE on preimplantation embryo development has not been reported. Here, we investigated whether and how DBDPE exposure affects preimplantation embryo development. Adult female mice were orally exposed to DBDPE (0, 5, 50, 500 µg/kg bw/day) for 14 days. First, we found that after DBDPE exposure, mice showed obvious circadian rhythm disorder. Moreover, the development of preimplantation embryos was inhibited in DBDPE-exposed mice after pregnancy. Then, we further explored and revealed that DBDPE exposure reduced the endogenous melatonin (MLT) level during pregnancy, thereby inhibiting the development of preimplantation embryos. Furthermore, we discovered that exogenous MLT supplementation (15 mg/kg bw/day) rescued the inhibition of preimplantation embryo development induced by DBDPE, and a mechanistic study demonstrated that exogenous MLT inhibited the overexpression of ROS and DNA methylation at the 5-position of cytosine (5-mC) in DBDPE-exposed preimplantation embryos. Simultaneously, MLT ameliorated the DBDPE-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential (MMP), ATP, and Trp1 expression. Additionally, MLT restored DBDPE-induced changes in zona pellucida (ZP) hardness and trophectoderm (TE) cortical tension. Finally, the protective effect of MLT on embryos ameliorated the adverse reproductive outcomes (dead fetus, fetus with abnormal liver, fetal weight loss) induced by DBDPE. Collectively, DBDPE induced preimplantation embryo damage leading to adverse reproductive outcomes, and MLT has emerged as a potential tool to rescue adverse reproductive outcomes induced by DBDPE.

Mild temperature photothermal assisted anti-bacterial and anti-inflammatory nanosystem for synergistic treatment of post-cataract surgery endophthalmitis.

Rationale: Endophthalmitis, which is one of the severest complications of cataract surgeries, can seriously threaten vision and even lead to irreversible blindness owing to its complicated microenvironment, including both local bacterial infection and severe inflammation. It is urgent to develop a comprehensive treatment for both anti-bacterial and anti-inflammatory effects. Methods: Herein, we developed AuAgCu2O-bromfenac sodium nanoparticles (AuAgCu2O-BS NPs), which was designed to combine anti-bacterial and anti-inflammatory effects for integrated therapy of endophthalmitis after cataract surgery. The AuAgCu2O-BS NPs could eradicate methicillin-resistant Staphylococcus aureus (MRSA) bacterial strain relied on their photodynamic effects and the release of metal ions (Ag+ and Cu+) by the hollow AuAgCu2O nanostructures mediated mild photothermal effects. The anti-inflammatory drug, bromfenac sodium, released from the nanoparticles were able to significantly reduce the local inflammation of the endophthalmitis and promote tissue rehabilitation. In vivo bacterial elimination and anti-inflammation were confirmed by a postcataract endophthalmitis rabbit model. Results: Excellent antibacterial ability of AuAgCu2O-BS NPs was verified both in vitro and in vivo. Ophthalmological clinical observation and pathologic histology analysis showed prominent treatment of inflammatory reaction. Importantly, the mild temperature photothermal effect not only promoted the release of metal ions and bromfenac sodium but also avoided the thermal damage of the surrounding tissues, which was more suitable for the practical application of ophthalmology due to the complex structure of the eyeball. Moreover, superior biocompatibility was approved by the preliminary toxicity investigations, including low cytotoxicity, negligible damage to major organs, and stable intraocular pressure. Conclusions: Our studies of nanosystem provide a promising synergic therapeutic strategy for postcataract endophthalmitis treatment with favorable prognosis and promise in clinical translations.

A comparison of the thyroid disruption induced by decabrominated diphenyl ethers (BDE-209) and decabromodiphenyl ethane (DBDPE) in rats.

In recent years, decabromodiphenyl ethane (DBDPE), a new alternative flame retardant to the decabrominated diphenyl ethers (BDE-209), is widely used in a variety of products. Previous studies have indicated that DBDPE, like BDE-209, could disrupt thyroid function. However, compared with BDE-209, the degrees of thyrotoxicosis induced by DBDPE were not clear. In addition, the mechanism of thyrotoxicosis induced by DBDPE or BDE-209 was still under further investigation. In this study, male rats as a model were orally exposed to DBDPE or BDE-209 by 5, 50, 500 mg/kg bw/day for 28 days. Then, we assessed the thyrotoxicosis of DBDPE versus BDE-209 and explored the mechanisms of DBDPE and BDE-209-induced thyrotoxicosis. Results showed that decreased free triiodothyronine (FT3) and increased thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) in serum were observed in both 500 mg/kg bw/day BDE-209 and DBDPE group. Decreased total thyroxine (TT4), total T3 (TT3), and free T4 (FT4) were only observed in BDE-209 group but not in DBDPE group. Histological examination and transmission electron microscope examination showed that high level exposure to BDE-209 and DBDPE both caused significant changes in histological structure and ultrastructure of the thyroid gland. Additionally, oxidative damages of thyroid gland (decreased SOD and GSH activities, and increased MDA content) were also observed in both BDE-209 and DBDPE groups. TG contents in the thyroid gland was reduced in BDE-209 group but not in DBDPE group. Both BDE-209 and DBDPE affected the expression of hypothalamic-pituitary-thyroid (HPT) axis related genes. These findings suggested that both BDE-209 and DBDPE exposure could disrupt thyroid function in the direction of hypothyroidism and the underlying mechanism was likely to be oxidative stress and perturbations of HPT axis. However, DBDPE was found to be less toxic than BDE-209.

Hepatoprotective Effects of the Honey of Apis cerana Fabricius on Bromobenzene-Induced Liver Damage in Mice.

Apis cerana honey (honey of Apis cerana Fabricius), widely distributed in the mountain areas of East Asia, has not been studied fully. The hepatoprotective activity of A. cerana honey was evaluated against bromobenzene-induced liver damage in mice. In high dose, A. cerana honey can significantly alleviate liver injury, as is indicated by the depressed levels of serum alanine aminotransferase (ALT) (59.13%) and aspartate aminotransferase (AST) (79.71%), the inhibited malondialdehyde (MDA) content (63.30%), the elevated activities of superoxide dismutase (SOD) (73.12%) and glutathione-Px (57.24%), and the decreased expression of Transforming growth factor ß1 (51.83%) induced by bromobenzene (P < 0.05). The quantitative analysis of twelve major constituents (1 to 12) of A. cerana honey was executed by high performance liquid chromatography-diode array detector. The results indicate that treatment with A. cerana honey can prevent bromobenzene-induced hepatic damage in mice. Polyphenols might be the bioactive substances attributed to its antioxidant properties and intervention of oxidative stress.

Applicability of Gas Chromatography (GC) Coupled to Triple-Quadrupole (QqQ) Tandem Mass Spectrometry (MS/MS) for Polybrominated Diphenyl Ether (PBDE) and Emerging Brominated Flame Retardant (BFR) Determinations in Functional Foods Enriched in Omega-3.

This paper reports on the optimization, characterization, and applicability of gas chromatography coupled to triple-quadrupole tandem mass spectrometry (GC-QqQ(MS/MS)) for the determination of 14 polybrominated diphenylethers (PBDEs) and 2 emerging brominated flame retardants, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and decabromodiphenylethane (DBDPE), in functional food samples. The method showed satisfactory precision and linearity with instrumental limits of detection (iLODs) ranging from 0.12 to 7.1 pg, for tri- to octa-BDEs and BTBPE, and equal to 51 and 20 pg for BDE-209 and DBDPE, respectively. The highest ΣBFR concentrations were found in fish oil supplements (924 pg/g fresh weight, fw), followed by biscuits (90 pg/g fw), vegetable oil supplements (46 pg/g fw), chicken eggs (45 pg/g fw), cow's milk (7.7 pg/g fw), and soy products (1.6 pg/g fw). BDE-47, BDE-99, and DBDPE were the most abundant compounds. Foodstuffs enriched with omega-3 presented concentrations similar to or even lower than those of conventional foods commercialized in Spain since 2000.

In situ derivatization-ultrasound-assisted dispersive liquid-liquid microextraction for the determination of neurotransmitters in Parkinson's rat brain microdialysates by ultra high performance liquid chromatography-tandem mass spectrometry.

Simultaneous monitoring of several neurotransmitters (NTs) linked to Parkinson's disease (PD) has important scientific significance for PD related pathology, pharmacology and drug screening. A new simple, fast and sensitive analytical method, based on in situ derivatization-ultrasound-assisted dispersive liquid-liquid microextraction (in situ DUADLLME) in a single step, has been proposed for the quantitative determination of catecholamines and their biosynthesis precursors and metabolites in rat brain microdialysates. The method involved the rapid injection of the mixture of low toxic bromobenzene (extractant) and acetonitrile (dispersant), which containing commercial Lissamine rhodamine B sulfonyl chloride (LRSC) as derivatization reagent, into the aqueous phase of sample and buffer, and the following in situ DUADLLME procedure. After centrifugation, 50µL of the sedimented phase (bromobenzene) was directly injected for ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection in multiple reaction monitoring (MRM) mode. This interesting combination brought the advantages of speediness, simpleness, low matrix effects and high sensitivity in an effective way. Parameters of in situ DUADLLME and UHPLC-MS/MS conditions were all optimized in detail. The optimum conditions of in situ DUADLLME were found to be 30µL of microdialysates, 150µL of acetonitrile containing LRSC, 50µL of bromobenzene and 800µL of NaHCO3-Na2CO3 buffer (pH 10.5) for 3.0min at 37°C. Under the optimized conditions, good linearity was observed with LODs (S/N>3) and LOQs (S/N>10) of LRSC derivatized-NTs in the range of 0.002-0.004 and 0.007-0.015 nmol/L, respectively. It also brought good precision (3.2-12.8%, peak area CVs%), accuracy (94.2-108.6%), recovery (94.5-105.5%) and stability (3.8-8.1%, peak area CVs%) results. Moreover, LRSC derivatization significantly improved chromatographic resolution and MS detection sensitivity of NTs when compared with the reported studies through the introduction of a permanent charged moiety from LRSC into NTs. Taken together, this in situ DUADLLME method was successfully applied for the simultaneous determination of six NTs in biological samples.

Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats.

OBJECTIVE: The purpose of the present study was to evaluate the nephroprotective and antioxidant properties of Triphala against bromobenzene-induced nephrotoxicity in female Wistar albino rats. METHODS: Animals were divided into five groups of six rats and treated as follows: Group I was a normal control and received no treatment, Group II received only bromobenzene (10 mmol/kg), Groups III and IV received bromobenzene and Triphala (250 and 500 mg/kg, respectively), Group V received Triphala alone (500 mg/kg), and Group VI received bromobenzene and silymarin (100 mg/kg). Antioxidant status and serum kidney functional markers were analyzed. RESULTS: Bromobenzene treatment resulted in significant (P< 0.05) decreases in the activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase as well as total reduced glutathione. There was a significant (P< 0.05) increase in lipid peroxidation in kidney tissue homogenates. There were significant (P< 0.05) reductions in the levels of serum total protein and albumin as well as significant (P< 0.05) increases in serum creatinine, urea and uric acid. The oral administration of two different doses (250 and 500 mg/kg) of Triphala in bromobenzene-treated rats normalized the tested parameters. The histopathological examinations of kidney sections of the experimental rats support the biochemical observations. CONCLUSION: Triphala treatment alleviated the nephrotoxic effects of bromobenzene by increasing the activities of antioxidant enzymes and reducing the levels of lipid peroxidation and kidney functional markers.

Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats / 中西医结合学报

<p><b>OBJECTIVE</b>The purpose of the present study was to evaluate the nephroprotective and antioxidant properties of Triphala against bromobenzene-induced nephrotoxicity in female Wistar albino rats.</p><p><b>METHODS</b>Animals were divided into five groups of six rats and treated as follows: Group I was a normal control and received no treatment, Group II received only bromobenzene (10 mmol/kg), Groups III and IV received bromobenzene and Triphala (250 and 500 mg/kg, respectively), Group V received Triphala alone (500 mg/kg), and Group VI received bromobenzene and silymarin (100 mg/kg). Antioxidant status and serum kidney functional markers were analyzed.</p><p><b>RESULTS</b>Bromobenzene treatment resulted in significant (P< 0.05) decreases in the activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase as well as total reduced glutathione. There was a significant (P< 0.05) increase in lipid peroxidation in kidney tissue homogenates. There were significant (P< 0.05) reductions in the levels of serum total protein and albumin as well as significant (P< 0.05) increases in serum creatinine, urea and uric acid. The oral administration of two different doses (250 and 500 mg/kg) of Triphala in bromobenzene-treated rats normalized the tested parameters. The histopathological examinations of kidney sections of the experimental rats support the biochemical observations.</p><p><b>CONCLUSION</b>Triphala treatment alleviated the nephrotoxic effects of bromobenzene by increasing the activities of antioxidant enzymes and reducing the levels of lipid peroxidation and kidney functional markers.</p>

Protective effect of administration of Withania somifera against bromobenzene induced nephrotoxicity and mitochondrial oxidative stress in rats.

BACKGROUND: The present study was conducted to elucidate the protective role of Withania somnifera against bromobenzene induced nephrotoxicity and mitochondrial dysfunction in rats. METHODS: In this study, Wistar albino rats of either sex were divided into six groups consisting of six animals each. The first one was control, those in group II received bromobenzene (10 mmol/kg, intragastric intubation) once, but group III and IV animals received W. somnifera (250 and 500 mg/kg, orally), respectively for 8 days followed by bromobenzene once on the 8th day and silymarin (100 mg/kg, orally) was given for 8 days to group V animals and then bromobenzene on the last day. Group VI animals received only W. somnifera (500 mg/kg) for 8 days. RESULTS: The levels of renal lipid peroxidation, lysosomal enzymes and glycoprotein were increased significantly (p<0.05) in the bromobenzene alone treated rats and antioxidant status and mitochondrial enzymes were found to be decreased, when compared to the control group. The levels of kidney functional markers (urea, uric acid and creatinine) were also found to be abnormal in serum of bromobenzene alone treated rats. On the other hand, administration of W. somnifera (250 and 500 mg/kg) along with bromobenzene offered a significant dose-dependent protection to the biochemical alterations as observed in the bromobenzene alone treated rats, which was also evidenced by histopathology. CONCLUSION: Thus, the oral administration of W. somnifera significantly protected against the bromobenzene induced nephrotoxicity and renal mitochondrial dysfunction in rats.

Cytotoxic Effects of a Novel Thialo Benzene Derivative 2,4-Dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) in L929 Cells.

The aim of this study was to compare the cytotoxic effects of a newly synthesized thialo benzene derivative 2,4-dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) and a well-known antifungal agent, fluconazole, in L929 cells. L929 cells were treated with 250, 500, or 1000 µg/mL of C18H12S2IBr and with the same doses of fluconazole. Cytotoxicity tests including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) leakage, and protein content were compared. Glucose and lactate concentrations were measured to determine alterations in metabolic activity. Apoptosis was investigated by TUNEL test and results were supported with survivin enzyme-linked immunosorbent assay. Treatment with C18H12S2IBr resulted in a concentration-dependent cytotoxicity as indicated by MTT, LDH leakage assay, and decreased protein concentration. The loss of cell viability and the increased LDH leakage in 500 µg/mL and 1000 µg/mL C18H12S2IBr and fluconazole groups indicated cell membrane damage and necrotic cell death. In all groups, metabolic activities were altered but apoptosis was not induced. We have previously investigated lower doses of C18H12S2IBr; there was no cytotoxicity in L929 cells. In this study, higher doses caused cytotoxicity and alterations in metabolic activity . When we consider the similar results obtained from fluconazole and especially the lowest dose of C18H12S2IBr, this newly synthesized compound may be a good alternative antifungal agent.

Biogenic synthesis of palladium nanoparticles using Pulicaria glutinosa extract and their catalytic activity towards the Suzuki coupling reaction.

Green synthesis of nanomaterials finds the edge over chemical methods due to its environmental compatibility. Herein, we report a facile and eco-friendly method for the synthesis of palladium (Pd) nanoparticles (NPs) using an aqueous solution of Pulicaria glutinosa, a plant widely found in a large region of Saudi Arabia, as a bioreductant. The as-prepared Pd NPs were characterized using ultraviolet-visible (UV-vis) spectroscopy, powder X-ray diffraction (XRD), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and Fourier transform-infrared spectroscopy (FT-IR). The hydroxyl groups of the plant extract (PE) molecules were found mainly responsible for the reduction and growth of Pd NPs. FT-IR analysis confirmed the dual role of the PE, both as a bioreductant as well as a capping ligand, which stabilizes the surface of Pd NPs. The crystalline nature of the Pd NPs was identified using XRD analysis which confirmed the formation of a face-centered cubic structure (JCPDS: 87-0641, space group: Fm3m (225)). Furthermore, the as-synthesized Pd NPs demonstrated excellent catalytic activity towards the Suzuki coupling reaction under aqueous and aerobic conditions. Kinetic studies of the catalytic reaction monitored using GC confirmed that the reaction completes in less than 5 minutes.

In vitro and in vivo antioxidant and antimutagenic activities of polyphenols extracted from hops (Humulus lupulus L.).

BACKGROUND: Hops (Humulus lupulus L.) contain 40-140 mg g(-1) polyphenols. The objective of this study was to determine the phenolic composition of a high-purity (total phenolic content = 887 mg g(-1) ) hop polyphenol extract (HPE) and evaluate its antioxidant activities in vivo and in vitro and its antimutagenic activity. The antioxidant activity of HPE was compared with the activity of green tea polyphenols. RESULTS: The phenolic compositions of HPE were more than 55% proanthocyanidins and more than 28% flavonoid glycosides. In vitro, HPE effectively scavenged α,α-diphenyl-ß-picrylhydrazyl, hydroxyl and superoxide anion radicals, and inhibited DNA oxidative damage. In vivo, oral HPE at a polyphenol dose of 200-800 mg kg(-1) body weight significantly prevented a bromobenzene-induced decrease in liver superoxide dismutase and glutathione peroxidase activity, and decreased levels of liver thiobarbituric acid reactive substances in bromobenzene-treated mice. An oral dose of 20-80 mg kg(-1) body weight HPE significantly reduced the frequency of bone marrow micronuclei induced by cyclophosphamide. The antioxidant activities of hop polyphenols in vitro and in vivo were higher than green tea polyphenols at the same concentration. CONCLUSION: Hop polyphenols had the same or higher antioxidant activity than tea polyphenols. Hop polyphenols might be useful as natural antioxidants and antimutagens.

Effects of black seed oil on resolution of hepato-renal toxicity induced bybromobenzene in rats.

OBJECTIVE: Volatile halocarbon, bromobenzene (BB), is frequently encountered in table-ready foods as contaminants residues. The objective of this study was to investigate whether black seed oil could attenuate hepato-renal injury induced by BB exposure. MATERIALS AND METHODS: The evaluation was done through measuring liver oxidative stress markers: reduced glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA). Hepatic succinate dehydrogenase (SDH), lactate dehydrogenases (LDH) and glucose-6-phosphatase (G-6-Pase) were estimated. Serum aspartate and alanine aminotransferases (AST, ALT) and alkaline phosphatase were also evaluated. Kidney function indices; blood urea nitrogen (BUN), creatinine, serum protein, nitric oxide (NO), Na-K-adenosine triphosphatase (Na+-K+-ATPase) and phospholipids were done. Liver and kidney histopathological analysis and collagen content were analyzed for results confirmation. RESULTS: Treatment with black seed oil (BSO) alleviated the elevation of GSH, SDH, LDH, G-6-Pase, serum protein, NO, Na+-K+-ATPase, phospholipids levels and attenuated MDA, SOD, AST, ALT and ALP. Diminution of collagen content and improvement in liver and kidney architectures were observed. CONCLUSIONS: BSO enhanced the hepato-renal protection mechanism, reduced disease complications and delayed its progression. Further studies are needed to identify the molecules responsible for its pharmacological effect.  

Subchronic hepatotoxicity evaluation of bromobenzene in Fischer 344 rats.

Male Fischer 344 (F344) rats were exposed to bromobenzene (BB) for 5 days and 2, 4 and 13 weeks. BB was administered by gavage (corn oil vehicle) at doses of 0, 25, 100, 200, 300 and 400 mg kg(-1) per day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood BB, gross pathology and liver histopathology. There were no BB exposure-related clinical signs of toxicity. Mean body weight decreased by 5-10% compared with control in the 400 mg kg(-1) per day group. Liver weight increases were dose- and exposure time-related and statistically significant at ≥25 mg kg(-1) per day. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were related to dose and exposure time. At early time points (5 days and 2 weeks), centrilobular inflammation, including granulomatous areas, and necrotic and anisokaryocytic hepatocytes were observed in rats of the two highest BB dose groups. Blood BB concentrations increased linearly with dose and at 13 weeks ranged from 8 to 136 µg ml(-1) (25-400 mg kg(-1) per day). In conclusion, rats administered BB doses up to 400 mg kg(-1) per day for up to 13 weeks had mild liver effects. A NOAEL of 200 mg kg(-1) per day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥ 400 mg kg(-1) per day.

Protective effect of Hemidesmus indicus L. R. Br. against bromobenzene-induced mitochondrial dysfunction in rat kidney.

Hemidesmus indicus (HI) is used in ancient Indian traditional herbal medicine to treat hepatic and renal disorders. The present study was designed to investigate the protective effect of HI aqueous extract against bromobenzene induced mitochondrial dysfunction in rat kidneys. Rats were administered bromobenzene with or without prior administration of HI or vitamin E. At the end of the experiment animals were sacrificed and kidneys were obtained to study mitochondrial function, oxidative stress parameters and histopathology. Administration of bromobenzene caused significant changes like: decrease in the mitochondrial respiration and P/O ratios, increase in lipid peroxidation and protein oxidation, and decrease in the activities of antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase and superoxide dismutase) in mitochondria with significant histopathological changes in the kidney. Prior administration of HI extract showed a significant protection against bromobenzene induced changes in the kidney and this effect is attributed to the antioxidant and free radical scavenging potential of the HI. The protection was much better with HI compared to vitamin E.

ARSyN: a method for the identification and removal of systematic noise in multifactorial time course microarray experiments.

Transcriptomic profiling experiments that aim to the identification of responsive genes in specific biological conditions are commonly set up under defined experimental designs that try to assess the effects of factors and their interactions on gene expression. Data from these controlled experiments, however, may also contain sources of unwanted noise that can distort the signal under study, affect the residuals of applied statistical models, and hamper data analysis. Commonly, normalization methods are applied to transcriptomics data to remove technical artifacts, but these are normally based on general assumptions of transcript distribution and greatly ignore both the characteristics of the experiment under consideration and the coordinative nature of gene expression. In this paper, we propose a novel methodology, ARSyN, for the preprocessing of microarray data that takes into account these 2 last aspects. By combining analysis of variance (ANOVA) modeling of gene expression values and multivariate analysis of estimated effects, the method identifies the nonstructured part of the signal associated to the experimental factors (the noise within the signal) and the structured variation of the ANOVA errors (the signal of the noise). By removing these noise fractions from the original data, we create a filtered data set that is rich in the information of interest and includes only the random noise required for inferential analysis. In this work, we focus on multifactorial time course microarray (MTCM) experiments with 2 factors: one quantitative such as time or dosage and the other qualitative, as tissue, strain, or treatment. However, the method can be used in other situations such as experiments with only one factor or more complex designs with more than 2 factors. The filtered data obtained after applying ARSyN can be further analyzed with the appropriate statistical technique to obtain the biological information required. To evaluate the performance of the filtering strategy, we have applied different statistical approaches for MTCM analysis to several real and simulated data sets, studying also the efficiency of these techniques. By comparing the results obtained with the original and ARSyN filtered data and also with other filtering techniques, we can conclude that the proposed method increases the statistical power to detect biological signals, especially in cases where there are high levels of structural noise. Software for ARSyN is freely available at http://www.ua.es/personal/mj.nueda.

Magneto-optical contrast in liquid-state optically detected NMR spectroscopy.

We use optical Faraday rotation (OFR) to probe nuclear spins in real time at high-magnetic field in a range of diamagnetic sample fluids. Comparison of OFR-detected NMR spectra reveals a correlation between the relative signal amplitude and the fluid Verdet constant, which we interpret as a manifestation of the variable detuning between the probe beam and the sample optical transitions. The analysis of chemical-shift-resolved, optically detected spectra allows us to set constraints on the relative amplitudes of hyperfine coupling constants, both for protons at chemically distinct sites and other lower-gyromagnetic-ratio nuclei including carbon, fluorine, and phosphorous. By considering a model binary mixture we observe a complex dependence of the optical response on the relative concentration, suggesting that the present approach is sensitive to the solvent-solute dynamics in ways complementary to those known in inductive NMR. Extension of these experiments may find application in solvent suppression protocols, sensitivity-enhanced NMR of metalloproteins in solution, the investigation of solvent-solute interactions, or the characterization of molecular orbitals in diamagnetic systems.

Protective effect of Cassia fistula fruit extract on bromobenzene-induced nephrotoxicity in mice.

The efficacy of a crude hydro-alcoholic extract of Cassia fistula (golden shower tree) fruit to protect the kidney against bromobenzene-induced toxicity was studied. Negative control mice received normal saline; positive control mice were given 460 mg/kg of bromobenzene; Cassia fistula treated mice received 200, 400, 600 and 800 mg/kg of Cassia fistula fruit extract followed by 460 mg/kg bromobenzene (daily by oral gavage for 10 days). On the 11th day, the mice were sacrificed, blood samples were obtained to assess blood urea nitrogen (BUN) and creatinine levels, and kidneys were removed for histological examination. We found that bromobenzene induced significant nephrotoxicity reflected by an increase in levels of BUN and creatinine that was dose dependently prevented by the Cassia fistula fruit extract. The nephroprotective effect of the Cassia fistula fruit extract was confirmed by the histological examination of the kidneys. To the best of our knowledge, this is the first study to demonstrate the protective effect of Cassia fistula in nephrotoxicity.

Protective effect of Cassia fistula fruit extract against bromobenzene-induced liver injury in mice.

In the present study, hepatoprotective effect of Cassia fistula fruit extract was investigated in mice. Animals were divided into six groups receiving normal saline (1), bromobenzene (460 mg/kg) alone (2) and together with increasing doses (200, 400, 600, 800 mg/kg) of a crude hydro-alcoholic extract of Cassia fistula fruit (3-6, respectively). All administrations were carried out orally, daily, for 10 days. On the 11th day, animals were sacrificed. Serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γGT) were determined; serum levels of direct and total bilirubin were measured; furthermore, livers were prepared for histological examination. Our results showed that bromobenzene treatment alone elicited a significant increase in activities of AST, ALT, ALP (but not γGT), and it significantly elevated the levels of direct and total bilirubin. Co-treatment with Cassia fistula fruit extract, however, significantly and dose-dependently decreased the above-mentioned enzyme activities (with exception of γGT) and bilirubin levels, producing a recovery to the naive state. The protective effect of Cassia fistula fruit extract against liver injury evoked by bromobenzene was confirmed by histological examination as well. In conclusion, the Cassia fistula fruit extract has significant hepatoprotective effect in our murine model.

Terrestrial toxicity evaluation of decabromodiphenyl ethane on organisms from three trophic levels.

Decabromodiphenyl ethane (DBDP-Ethane) was evaluated for its potential to effect sewage sludge respiration, soil nitrification, survival and reproduction in Eisenia fetida, and seedling emergence and growth in Zea mays, Lolium perenne, Glycine max, Allium cepa, Lycopersicon esculentum, and Cucumis sativa. The no observed effect concentrations (NOECs) were identified at the limit concentration level for sewage sludge respiration (>10 mg DBDP-Ethane/kg dry soil), >2500 mg/kg dry soil for soil nitrification, >3720 mg/kg dry soil for earthworm survival, and >6250 mg/kg dry soil for seedling emergence and growth in Z. mays, L. perenne, and G. max . Treatment-related effects were identified for E. fetida reproduction, C. sativa survival, and L. esculentum and A. cepa height and dry weight. The most sensitive endpoints were decreased height and dry weight for A. cepa and decreased reproduction for E. fetida with NOECs of 1563(nominal) (1540(measured)) and 2210(nominal) (1907(mean measured)) mg/kg dry soil. The NOEC for soil nitrification and the lowest NOEC identified for soil (i.e., A. cepa) were used to derive predicted no effect concentrations (PNEC) values of 2500 mg/kg for sewage sludge and 156 mg/kg for soil. The calculated PNECs indicate DBDP-Ethane presents little risk to organisms in the sewage sludge and soil compartments.