A New Functional Wheat Flour Flatbread (Bazlama) Enriched with High-ß-Glucan Hull-Less Barley Flour.

Although the Med-Diet is a healthy diet model, it is affected by current dietary habits. Therefore, new foods with improved nutritional value should be developed to respond to the needs of people following the Med-Diet. This study was focused on developing high-ß-glucan flat bread (bazlama) with a relatively lower GI. A bread wheat (cv. Tosunbey) flour was enriched with the flour of a high-ß-glucan-content hull-less barley (cv. Chifaa) flour (15, 30, 45 and 60%) to develop a functional bazlama. The nutritional and technological properties of bazlama samples enriched with barley flour were compared with the ones produced from bread wheat. All of the barley flour-enriched bazlama samples had higher yellowness values (b*) than the control (both crumb and crust), which is generally preferred by the consumers. Texture results indicated that bazlama samples became harder with the increase in barley flour supplementation level. The results showed that 3 g of ß-glucan can be provided from the barley flour-enriched bazlama samples (at 45 and 60% levels), and this is the limit to carry health claims. The bazlama samples enriched with barley flour were richer in Mg, K, Mn, Fe, and Zn minerals than the control (100% Tosunbey flour). While the glycemic index (GI) of commercial bread wheat and Tosunbey bazlama samples were high (88.60% and 79.20%, respectively), GI values of the bazlama samples enriched with 60% (64.73) and 45% barley flour (68.65) were medium. The lower GI values of barley flour-enriched bazlama samples are probably due to the higher ß-glucan contents of the bazlama samples. Additionally, as the barley flour supplementation level of the bazlama samples increased, the phenolics and antioxidant capacities of free and bound extracts increased compared to bread wheat bazlama. The results indicated that hull-less barley (cv. Chifaa) with high ß-glucan content may be utilized at relatively higher levels (45 and 60%) to produce bazlama with improved nutritional properties.

ß-Glucan Regulates Lipopolysaccharide Induced Genotoxic Damage to The Liver through The Induction of BRCA1 Protein Expression.

OBJECTIVE: The present study aims to investigate the role of breast cancer-susceptibility gene 1 (BRCA1) protein in the ß-Glucan (ßG) molecule mediated regulation of lipopolysaccharide (LPS)-induced liver genotoxicity. MATERIALS AND METHODS: In this experimental study, totally, 32 male Swiss Albino mice were randomly divided into 4 equal groups: control (C), LPS-administered (LPS), ßG-administered (ßG) and ßG-pre-administered/LPS-administered (ßG+LPS). The ßG was injected at the dose of 150 mg/kg/day intraperitoneally (i.p.) for 3 days. A single dose of 4 mg/ kg (i.p.) LPS was administered 24 hours after the last ßG injection. BRCA1 expression was determined by western blot analysis and confirmed by quantitative immunofluorescence. Proliferating cell nuclear antigen (PCNA), nuclear factor erythroid 2-related factor (Nrf2) and 8-OHdG protein levels were also determined by the immunofluorescence analysis. The alkaline comet assay was performed. superoxide dismutase (SOD), catalase (CAT) and membrane lipid peroxidation were biochemically measured, and light microscopic histology was evaluated. RESULTS: The BRCA1 expression level was significantly decreased in the LPS group. However, in the ßG+LPS group, expression of BRCA1 protein was over 2 folds higher than the control. After the LPS induction, the DNA strand breaks, oxidative DNA lesions and abnormal proliferation of the liver cells were almost entirely suppressed in ßG preadministrated animals, indicating the BRCA1 mediated ubiquitination of PCNA and activation of the DNA damage repair pathways. Activation of Nrf2 in the ßG+LPS group resulted in an increase in the levels of Nrf2 pathway dependent antioxidant enzymes SOD and CAT, prevented the peroxidation of membrane lipids and maintained the histological architecture of the liver. CONCLUSION: The results manifested that the ßG is a strong inducer of the BRCA1 protein expression in the LPSinduced hepatic stress and the protein constitutes the key component of a ßG mediated liver protection against an LPS-induced genotoxic and pathological damage.

Two new dihydroisocoumarins and terpenoids from Scorzonera longiana Sümbül an endemic species to Turkey and their antimicrobial activity.

Two new dihydroisocoumarins (scorzolongin I (1), and scorzolongin II (2)) and nine known compounds (3',5'-dimethoxy hydrangenol (scorzolongin III, 3), cladantholide (4), dammar-24-ene-3ß-ol (5), taraxasterol (6), ß-sitosterol (7), mangifgerursanone (8), and a mixture of α-amyrenone (9a), ß-amyrenone (9b), and dammar-24-ene-3-one (9c) in about 1:1:2 ratio) were identified from the dichloromethane fraction of Scorzonera longiana. The structure of all compounds (1-9a-c) were elucidated by extensive 1D and 2D NMR (1H, 13C/APT, COSY, HMBC, HSQC, and NOESY) spectroscopy, UV, FT-IR, and LC-QTOF-MS data and by comparison of their NMR data with the literature. These compounds have been isolated from S. longiana for the first time. An antimicrobial assay against eight microorganisms was applied to isolated compounds 1-3. Scorzolongin I, and scorzolongin II, and scorzolongin III showed notable activity against gram (-) (Escherichia coli and Yersinia pseudotuberculosis) and fungi (Candida albicans, Saccharomyces cerevisiae) with 20 mm inhibition zone each. Scorzolongin II (2) exhibited strong activity against E. coli, Y. pseudotuberculosis, Mycobacterium smegmatis C. albicans, S. cerevisiae with MIC value of 33.8 µg/mL.

Effects of quetiapine administration on sperm quality and testicular histology.

Quetiapine is one of the most commonly prescribed antipsychotics to treat schizophrenia in adults, in particular. In this study, quetiapine's effects were assessed on healthy sperm production in rats at repeated-pharmacological doses. Additionally, the effects of quetiapine on oxidative status and hormonal balance were also evaluated in rats. Quetiapine was administered to rats orally at 10, 20, and 40 mg/kg body weight doses for 28 days. At the end of this period, body and organ weights were measured, sperm concentration, motility, and morphology were determined, sperm damage was assessed, and histopathological analysis of testicular tissue was performed. Additionally, serum FSH, LH, and testosterone levels as male reproductive hormones were measured. Catalase, superoxide dismutase, glutathione, and malondialdehyde levels were determined for evaluating the oxidative status of testicular tissue. The findings obtained in this study showed that relative epididymis weights and sperm concentration decreased and abnormal sperm morphology increased in quetiapine-administered rats. Irregularity of typical architecture of the seminiferous tubules and germinal cell disorganization was observed in testicular sections of 20 and 40 mg/kg quetiapine-administered rats. Further, serum LH and testosterone levels decreased in 20 and 40 mg/kg quetiapine-administered rats. Additionally, decreased catalase and superoxide dismutase activities in testicular tissue of quetiapine-administered rats and increased malondialdehyde levels in testicular tissue of 40 mg/kg quetiapine-administered rats were measured. In conclusion, quetiapine treatment decreased sperm quality, altered hormone levels, and induced oxidative stress may be considered potential contributors to this adverse effect.

Chemical Variation, Antimicrobial, Nitric Oxide Scavenging Activities and Tyrosinase Inhibition of Essential Oils and Solvent Extracts from Filipendula vulgaris Moench Growing in Turkey.

Volatile organic compositions of the essential oils (EOs), solid-phase microextraction (SPME) and SPME of n-hexane extracts from the flower and stem-leaf of Filipendula vulgaris (F. vulgaris) were analyzed by GC-FID/MS. A total of 107 constituents were characterized, flower and stem-leaf parts of the plant were found to contain different volatile organic compounds. Tricosane (29.6%), n-nonanal (20.5%) were identified as the main components in the essential oil of the flower, while phytol (35.2%) was found to be a major constituent in the essential oil of stem-leaf. Benzaldehyde (56.0%) and n-nonanal (31.6%) were the major groups in the SPME of stem-leaf and flower, respectively. The volatiles for the SPME of n-hexane extracts of the flower and stem-leaf of F. vulgaris were predominated by aromatic compounds (75.0% and 78.5%) and ketones (18.1% and 10.1%), respectively. On the other hand, a total of terpene compounds was found at the most in the EO of the stem-leaf part of the plant (48.6%). In addition, antimicrobial, tyrosinase inhibition, and nitric oxide scavenging activities of the n-hexane (H), methanol (M), aqueous extracts (A) and EOs of F. vulgaris were investigated. EOs and methanol extracts of flower and stem-leaf had high antimicrobial activity against tested various microorganisms. However, n-hexane extracts of the flower and stem-leaf only displayed activity against Mycobacterium smegmatis. Methanol extracts of flower and stem-leaf possessed the best tyrosine inhibition and NO scavenging activity.

Effects of different molecular subtypes and tumor biology on the prognosis of medulloblastoma.

PURPOSE: Medulloblastoma is one of the most common malignant brain tumors in the pediatric population. Recent studies identified four distinct medulloblastoma subgroups with different molecular alterations and pathways, and natural courses and outcomes. To evaluate the results of surgical and medical treatments of patients with medulloblastoma and compare them among the medulloblastoma subgroups. METHODS: The clinical and radiological features, medical and surgical management and treatment outcomes and their correlation with molecular subgroups of 58 patients treated for medulloblastoma in the last 20 years were evaluated. RESULTS: Fifty-eight patients, of whom 35 were male and 23 were female, were evaluated. The median age was 6 years (range, 1-19 years). The most common symptoms were nausea and vomiting (60%). Forty-three percent of the patients had headache and 40% had ataxia. Previous pathology reports revealed that 43 (74%), eight (14%), five (8%), and two (3%) had classic, desmoplastic, desmoplastic/nodular, and anaplastic morphologies, respectively. After the subgroup analyses, five patients (12%) were attributed to the wingless subgroup (WNT) group; 14 (32.5%), to the sonic hedgehog subgroup (SHH) group; and 24 (56%), to the non-WNT non-SHH group. On the basis of immunohistochemical analysis results, 15 patients could not be attributed to any subgroups. The clinical risk groups (average vs high-risk) and age at diagnosis (≥ 3 years vs < 3 years of age) were significant for 5-year event free survival (86% vs 43%, p:0.011 and 59% vs 36%, p:0.039). There was no significant difference in survival or event free survival according to molecular subtypes in this cohort. CONCLUSION: In corporation of molecular features to the clinicopathologic classification leads to risk-adapted treatment. Although the molecular subgroups did not affect outcome significantly in this study, more studies with larger numbers of patients are needed to understand the tumor pathophysiology of medulloblastoma and design the future medical practice.

Synthesis, biological evaluation (antioxidant, antimicrobial, enzyme inhibition, and cytotoxic) and molecular docking study of hydroxy methoxy benzoin/benzil analogous.

In this work, due to the biological activity evaluation, a series of hydroxy methoxy benzoins (1-8), benzils (10-16) and methoxy benzoin/benzil-O-ß-d-glucosides (17-28) were synthesized. Antioxidant (FRAP, CUPRAC, DPPH), antimicrobial (16 microorganisms, and two yeast), enzyme inhibition (α-amylase, α-glucosidase, AChE, BChE, and tyrosinase) of all synthesized benzoin/benzil analogs were investigated. Benzoins (1-8) showed the most effective antioxidant properties compared to all three methods. Compound 28 against α-amylase, compound 9 against α-glucosidase, compound 11 against AChE, compound 2 against BChE, and compound 13 against tyrosinase showed the best activities with the better or similar IC50 values as used standards. Hydroxy methoxy benzoin compounds (1-8) among all four groups were seen as the most effective against the tested microorganism. Molecular docking analysis showed that all tested compounds 1-28 (0.01-2.22 µM) had the best binding affinity against AChE enzyme. Cytotoxic effects of the many of compounds (1-16, 21, and 24) also investigated and it was found that they caused different effects in different cells. The LDH tests of compounds 1a + b, 4, 7, 8, 9, 11, 12, 21, and 24, seemed to be effective compared to the positive control cisplatin. The cytotoxicity of compounds 6 (9.24%) for MCF7 cancer cells, 8 (5.16%) and 4 (8.26%) for HT29 cancer cells, 24 (9.84%) for Hep3B cells and 8 (8.52%), 7 (5.70%), 4 (6.94) and 9 (7.22%) for C6 cells were at normal values. And also cytotoxic activity of four compounds (5, 9, 21, and 24) among the all synthetic groups, were evaluated to the HeLa and RPE. Compound 5 showed anticancer activity on HeLa and RPE cancer cells as much as or better than cisplatin which was used as standard.

Olanzapine induced reproductive toxicity in male rats.

Although it is reported that olanzapine (OLZ), which is an atypical antipsychotic drug, causes sexual dysfunction in men, it is noteworthy that there is not any study evaluating the toxic effects of OLZ on the male reproductive system. In the scope of this research, it was aimed to assess the reproductive toxic effects of OLZ by oral administration of 2.5, 5, or 10 mg/kg of it to male rats for 28 days. For this purpose, sperm concentration, motility and morphology, and DNA damage were determined, and histopathological examination of testis tissue was carried out in rats. Also, the levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, which play roles in the regulation of reproductive functions, and the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) which play roles in reproductive pathologies as oxidative stress biomarkers, were determined. According to the results, normal sperm morphology was decreased in 5 ve 10 mg/kg OLZ-administered groups, and pathological findings were evident in the testicular structure of the OLZ-administered group when compared with the control group. It was determined that serum LH, FSH, and testosterone levels were decreased in the OLZ-administered group. Also, decreases of GSH levels in testis tissue were determined and evaluated as the markers of the oxidative stress induced by OLZ in the testis. In conclusion, it was determined that reproductive toxic effects were induced in rats by OLZ administration. This pathology was accompanied by alterations of the hormone levels and testicular oxidative stress.

Synthesis of hydroxy benzoin/benzil analogs and investigation of their antioxidant, antimicrobial, enzyme inhibition, and cytotoxic activities.

In this study, hydroxy benzoin ( 1-7 ), benzil ( 8-14 ), and benzoin/benzil-O-ß-D-glucosides ( 15-25 ) were synthesized to investigate their biological activities. An efficient method for synthesizing hydroxy benzoin compounds ( 1 - 7 ) was prepared from four different benzaldehydes using an ultrasonic bath. Then, antioxidant (FRAP, CUPRAC, and DPPH), antimicrobial (3 Gram (-), 4/6 Gram (+), one tuberculosis and one fungus), and enzyme inhibition (acetylcholinesterase, butyrylcholine esterase, tyrosinase, α-amylase, and α- glucosidase) for the all synthesized compounds ( 1-25 ) were evaluated. And also, four most active compounds ( 4 , 12 , 18a+b , and 25 ) from each group were evaluated to the human cervical cancer cell line (HeLa) and anticancer screening tests against the human retinal normal cell line (RPE). Compound 4 showed HeLa and RPE cancer cell activities as much as cisplatin. The synthesized compounds were characterized by spectroscopic methods (NMR, FT-IR, UV, LC-QTOF-MS) and the ACD NMR program's help.

Risperidone induced reproductive toxicity in male rats targeting leydig cells and hypothalamic-pituitary-gonadal axis by inducing oxidative stress.

Risperidone (RIS), a commonly used drug during a lifetime for the treatment of schizophrenia, causes some adverse effects in the male reproductive system; however, there is no comprehensive reproductive toxicity study of RIS. For this purpose, male rats were administered orally for 1.25, 2.5 and 3 mg/kg RIS for 28 days and the sperm count, motility, morphology, DNA damage and the histological changes in testicular tissue were evaluated. Follicle-stimulating hormone (FSH), luteinising hormone (LH) and serum levels of testosterone, which are the main hormonal regulators of reproduction, and testicular glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) levels as the indicators of oxidative stress were determined. Normal sperm morphology was decreased in RIS groups and histopathological degeneration occurred in testis tissue dose-dependently. Serum LH levels were not altered; however, FSH and testosterone levels decreased in the high-dose group. Histopathologic examination showed RIS toxicity targeted Leydig cells, which might be associated with impairment of the hypothalamic-pituitary-gonadal (HPG) axis. GSH levels were decreased and MDA levels were increased in the high-dose group which was evaluated as indicators of oxidative stress. In conclusion, RIS caused reproductive toxicity in male rats by inducing oxidative stress and disrupting hormonal regulation.

Chemical composition, antimicrobial, and lipase enzyme activity of essential oil and solvent extracts from Serapias orientalis subsp. orientalis.

The volatile components of essential oil (EO), SPME, and SPME of solvent extracts ( n -hexane, methanol, and water) obtained from fresh Serapias orientalis subsp. orientalis ( Soo ) were analyzed by GC-FID/MS. EO of Soo gave 11 compounds in the percentage of 99.97%; capronaldehyde (37.01%), 2-( E )-hexenal (23.19%), and n -nonanal (19.05%) were found to be major constituents. SPME GC-FID/MS analyses of fresh plant and solvent extracts of Soo revealed 7, 12, 7, and 4 compounds within the range of 99.7% to 99.9%. Limonene (76.5%, 41.7%, and 61.3%) was the major compound in SPMEs of the n -hexane and methanol extracts. α -Methoxy- p -cresol (52.9%) was the main component in its water extract. The antimicrobial activity of EO and the solvent extracts of Soo were screened against 9microorganisms. EO showed the best activity against Mycobacterium smegmatis , with 79.5 µg/mL MIC value. The n -hexane, methanol, and water extracts were the most active against the Staphylococcus aureus within the range of 81.25-125.0 µg/mL (MIC). IC 50 values for the lipase enzyme inhibitory activity of EO and solvent extracts ( n -hexane, methanol, and water) were determined to be 59.87 µg/mL, 64.03 µg/mL, 101.91 µg/mL, and 121.24 µg/mL, respectively.

Corrigendum to "Toxic Effects of Trazodone on Male Reproductive System via Disrupting Hypothalamic-Pituitary-Testicular Axis and Inducing Testicular Oxidative Stress".

[This corrects the article DOI: 10.1155/2018/7196142.].

Evidence for cardiotoxicity associated with sertraline in rats.

Sertraline is an antidepressant that is frequently prescribed to treat depression, obsessive-compulsive disorder, panic disorder, and anxiety. This drug had a safe cardiotoxicity profile, until the reporting of cases of sertraline-associated cardiotoxicities in the early 2000s. Since then, there have been conflicting results on the cardiotoxicity of this drug. In the study reported here we aimed to identify the cardiotoxic effects of sertraline by evaluating serum cardiac biomarkers, such as serum aspartate aminotransferase (AST), creatinine phosphokinase-myoglobin band (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin T (cTn-T) levels as well as electrocardiographic parameters, DNA damage in cardiomyocytes, and histological findings of heart tissue in rats that were administered oral doses of 5, 10, or 20 mg kg-1 of sertraline for 28 days. Additionally, to investigate the possible mechanisms underlying cardiotoxicity, glutathione and malondialdehyde levels in cardiac tissue were determined to evaluate oxidative stress. According to our results, AST, LDH, and cTn-T levels were significantly increased in the 10 and 20 mg kg-1 sertraline groups when compared to the control group. Heart rates were increased, PR intervals prolonged, a short QTc value was observed, and T-wave amplitudes were decreased significantly in the 20 mg kg-1 sertraline group when compared to the control group. Significant DNA damage was observed in the high-dose groups. Histopathological investigations also revealed some degenerative changes in the 10 and 20 mg kg-1 sertraline groups. Glutathione levels were significantly decreased in the 10 and 20 mg kg-1 sertraline groups when compared with the control group. In conclusion, our findings support the cardiotoxic potential of sertraline and also suggest that oxidative stress may play a role in the toxicity of sertraline.

Toxic Effects of Trazodone on Male Reproductive System via Disrupting Hypothalamic-Pituitary-Testicular Axis and Inducing Testicular Oxidative Stress.

Depression and anxiety are recognized as public health problems. Epidemiological studies have shown that depression and anxiety often occur during reproductive ages between 20 and 60 years of age in males. Trazodone is one of the most frequently prescribed drugs in the treatment of depression and anxiety. Drugs used in repeated doses also play a role in the etiology of infertility. In our study, it was aimed to identify the possible toxic effects of trazodone on male rats and elucidate the underlying mechanisms. Vehicle or trazodone (5, 10, and 20 mg/kg/day) was administered to rats for 28 consecutive days (n = 8 per group). At the end of that period, sperm concentration, motility, morphology, and DNA damage were determined and testicular morphology was assessed histopathologically in rats. Additionally, we investigated hormonal status by determining serum testosterone, FSH, and LH levels and oxidative stress by determining glutathione and malondialdehyde levels in testicular tissue to elucidate mechanisms of possible reproductive toxicity. According to our results, sperm concentration, sperm motility, and normal sperm morphology were decreased; sperm DNA damage was increased in trazodone-administered groups. Degenerative findings on the testicular structure were observed after trazodone administration in rats. Additionally, serum FSH, LH, and testosterone levels were elevated in the trazodone-administered groups. Increased MDA levels were the signs of enhanced oxidative stress after trazodone administration in testis tissues. Thus, we concluded that trazodone induced reproductive toxicity in male rats; this reproductive toxicity was accompanied by oxidative stress and hormonal changes, which are considered as important causes of reproductive disorders.

Application of affinity microspheres for effective SPE cleanup before the determination of sulfamerazine by HPLC.

This paper describes the application of poly (ethylene glycol dimethacrylate-N-methacryloyl-L-tryptophane methyl ester) [p(EGDMA-MATrp)] microspheres as an affinity sorbent for the SPE (solid phase extraction) cleanup of sulfamerazine (SMR) from food samples of animal origin before high performance liquid chromatography (HPLC) analysis. The microspheres were prepared by suspension polymerization of ethylene glycol dimethacrylate (EGDMA) and N-methacryloyl-L-tryptophane methyl ester (MATrp) as a crosslinker and a monomer, respectively. Various parameters affecting the SPE cleanup efficiency of the p(EGDMA-MATrp) microspheres (contact time, pH, initial SMR concentration, ionic strength etc.) were optimized. Under the optimized conditions, maximum adsorption capacity was found to be 8.55 ±â€¯0.44 mg/g sorbent at pH 5.0. 90% of the adsorbed SMR was desorbed by using ACN:MeOH (5:5) mixture as a desorption agent. Applicability of the microspheres for the SPE cleanup of SMR residues in the food samples such as egg and milk with HPLC was also determined. It was demonstrated that the prepared p(EGDMA-MATrp) microspheres could be repeatedly applied for SPE cleanup of sulfamerazine before chromatographic analysis. Also, the recoveries of SMR in milk and egg samples were reasonably satisfactory and in the range of 71 to 90%.

Neurotoxicity assessment of oleic acid-coated iron oxide nanoparticles in SH-SY5Y cells.

Iron oxide nanoparticles (ION) awaken a particular interest for biomedical applications due to their unique physicochemical properties, especially superparamagnetism, and ability to cross the blood-brain barrier. ION surface can be coated to improve their properties and facilitate functionalization. Still, coating may affect toxicity. The aim of this work was to evaluate the possible effects of oleic acid-coated ION (O-ION) on human neuronal cells (SH-SY5Y). A set of assays was conducted in complete and serum-free culture media for 3 and 24 h to assess O-ION cytotoxic effects - cell membrane disruption, cell cycle alteration and cell death induction -, and genotoxic effects - primary DNA damage, H2AX phosphorylation and micronuclei induction -, considering also DNA repair competence and iron ion release. Results obtained show that O-ION exhibit a moderate cytotoxicity related to cell membrane impairment, cell cycle disruption and cell death induction, especially notable in serum-free medium. Iron ion release was only observed in complete medium, indicating that cytotoxicity observed was not related to the presence of ions in the medium. However, O-ION genotoxic effects were limited to the induction of primary DNA damage, not related to double strand breaks, and this damage did not become fixed in cells in most conditions. Alterations in repair ability (DNA repair competence assay) were observed when cells where treated with O-ION before or during the challenge with H2O2, but not during the repair period. Further investigation is needed to clarify the possible role of oxidative stress and protein corona on observed O-ION toxicity.

Toxicological assessment of silica-coated iron oxide nanoparticles in human astrocytes.

Iron oxide nanoparticles (ION) have great potential for an increasing number of medical and biological applications, particularly those focused on nervous system. Although ION seem to be biocompatible and present low toxicity, it is imperative to unveil the potential risk for the nervous system associated to their exposure, especially because current data on ION effects on human nervous cells are scarce. Thus, in the present study potential toxicity associated with silica-coated ION (S-ION) exposure was evaluated on human A172 glioblastoma cells. To this aim, a complete toxicological screening testing several exposure times (3 and 24 h), nanoparticle concentrations (5-100 µg/ml), and culture media (complete and serum-free) was performed to firstly assess S-ION effects at different levels, including cytotoxicity - lactate dehydrogenase assay, analysis of cell cycle and cell death production - and genotoxicity - H2AX phosphorylation assessment, comet assay, micronucleus test and DNA repair competence assay. Results obtained showed that S-ION exhibit certain cytotoxicity, especially in serum-free medium, related to cell cycle disruption and cell death induction. However, scarce genotoxic effects and no alteration of the DNA repair process were observed. Results obtained in this work contribute to increase the knowledge on the impact of ION on the human nervous system cells.

Cytotoxicity screening and cytokine profiling of nineteen nanomaterials enables hazard ranking and grouping based on inflammogenic potential.

Engineered nanomaterials (ENMs) are being produced for an increasing number of applications. Therefore, it is important to assess and categorize ENMs on the basis of their hazard potential. The immune system is the foremost defence against foreign bodies. Here we performed cytokine profiling of a panel of nineteen representative ENMs procured from the Joint Research Centre (JRC) and commercial sources. Physicochemical characterization was performed using dynamic light scattering. The ENMs were all shown to be endotoxin content free. The human macrophage-differentiated THP.1 cell line was employed for cytotoxicity screening and based on the calculated IC50 values, the multi-walled carbon nanotubes (MWCNTs), ZnO, Ag and SiO2 NMs were found to be the most cytotoxic while single-walled carbon nanotubes (SWCNTs), TiO2, BaSO4 and CeO2 NMs, as well as the nanocellulose materials, were non-cytotoxic (at doses up to 100 µg/mL). Multiplex profiling of cytokine and chemokine secretion indicated that the TiO2, SiO2, BaSO4, CeO2 and nanocellulose materials induced potent inflammatory responses at sub-cytotoxic doses. Hierarchical clustering of cytokine responses coupled with pathway analysis demonstrated that the panel of ENMs could be segregated into two distinct groups characterized by activation and deactivation, respectively, of PPAR (peroxisome proliferator-activated receptor)/LXR (liver X receptor/retinoid X receptor) nuclear receptor pathways (NRPs). Furthermore, using rosiglitazone, a selective PPAR-γ agonist, we could show that PPAR-γ played an important role in the activation of inflammatory responses in cells exposed to TiO2 and SiO2 NMs. These studies show that ENMs of diverse chemical compositions can be grouped according to their inflammatory potential.

Citalopram Induces Reproductive Toxicity in Male Rats.

BACKGROUND: Citalopram hydrobromide (CTL) has been shown to cause sexual dysfunction; however, its reproductive toxicity potential has not been sufficiently elucidated in men. Therefore, we aimed to clarify the toxic effects of CTL on the reproductive system of male rats. METHODS: For this purpose, CTL was administered at 5, 10, and 20 mg/kg/day to rats orally for 28 days. Sperm concentration, motility, and morphology were investigated using a computer-assisted sperm analysis system, and sperm DNA damage was detected using a Comet assay. The testes were histopathologically examined. Serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels were measured and the oxidative status of testes was investigated. RESULTS: Our results showed that sperm concentration was reduced, and abnormal sperm morphology and sperm DNA damage were increased in CTL-administered groups. Additionally, histopathological changes were observed in the testes of CTL-administered rats. Luteinizing hormone levels were increased in CTL-administered groups, while testosterone levels were increased in the 5 and 10 mg/kg CTL-administered groups. Decreased glutathione signaled enhanced oxidative stress in the 10 and 20 mg/kg CTL-administered groups. CONCLUSION: Thus, we concluded that CT induced testicular damage in male rats; this testicular damage was accompanied by oxidative stress and hormonal changes, which are considered as the important causes of reproductive disorders. Birth Defects Research 109:475-485, 2017. © 2017 Wiley Periodicals, Inc.

Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress.

Levetiracetam (LEV) is an antiepileptic drug commonly used in the treatment of epilepsy because of its excellent safety profile in all age groups. It is remarkable that there are no studies evaluating the toxic effects of this drug on the male reproductive system, as it is commonly used in male patients of reproductive age. From this point of view, our aim was to evaluate the possible toxic effects of LEV on the male reproductive system. Therefore, LEV was administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive days. At the end of this period, alterations to body and organ weights were calculated, and sperm concentration, motility, and morphology were investigated by a computer-assisted sperm analysis system. Sperm DNA damage was determined by comet assay and histopathological examination of the testes was carried out. Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured by ELISAs to determine the effects of hormonal status, while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in the testes were measured by colorimetric assay kits to determine the role of oxidative status in potential toxicity. According to the results, sperm quality was decreased by LEV treatment in a dose-dependent manner. LEV induced significant DNA damage in the 150 and 300 mg/kg LEV-administered groups. Histopathology of the testes showed that LEV resulted in testicular injury in the 300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were significantly decreased in the 300 mg/kg LEV-administered group. Glutathione, superoxide dismutase, and catalase levels were significantly decreased in all experimental groups while malondialdehyde levels were significantly increased in 150 and 300 mg/kg LEV-administered groups. According to these results, it was determined that LEV administration decreased sperm quality and it was alleged that hormonal alteration and oxidative stress are potential contributors to reproductive toxicity.