Cytotoxic effects of dose dependent inorganic magnesium oxide nanoparticles on the reproductive organs of rats.

INTRODUCTION: Magnesium oxide nanoparticles (MgO NPs) have a variety of applications that have contributed to their elevated popularity, however, the safety and toxic effects on humans are also of concern with these increased applications. There is insufficient data regarding the effect of MgO NPs on reproductive organs, which are crucial aspects to the body's vital physiological functions. The present study was undertaken in male and female rats to assess the reproductive toxicological potential of two doses (low versus high) of MgO NPs on testicular and ovarian tissues. The toxicity was evaluated using histological, hormonal, and oxidative parameters. MATERIAL AND METHODS: In this work, magnesium oxide nanoparticles (MgO NPs) were synthesized by the sol-gel route and were characterized by X ray diffraction analysis (XRD) and Fourier transform infra-red spectroscopy (FTIR). Forty-eight adult Wister albino rats were used in this experiment which were divided into groups of male and female, and then further into control, low dose MgO NPs, and high dose MgO NPs. The low dose used was 131.5 mg/kg b.w. (1/10 LD50) while the high dose used was 263 mg/kg b.w. (1/5 LD50). All doses were given orally by gastric tube. After 4 weeks, blood samples were collected to investigate the level of sex hormones and both ovarian and testicular tissues were examined for variable oxidative parameters and histopathological changes by light microscopy. RESULTS: The obtained findings showed that high dose of MgO NPs produced considerable changes in sex hormones and stress parameters in both male and female rats in comparison to the low dose and control groups. Histomorphometric analysis demonstrated the presence of histopathological alterations in the testicular and ovarian tissues. CONCLUSION: The results of this study showed dose-dependent adverse effects of MgO NPs on the testis and ovary both functionally and histopathologically as compared to the control rats.

The potential protectivity of honey and olive oil in methotrexate induced renal damage in rats.

Methotrexate (MTX) is an antimetabolite used to treat inflammatory diseases, autoimmune disorders and some malignancies. However, it has some life-threatening side effects such as nephrotoxicity which limit its clinical applications. That motivated the attention to seek for a defensive material to improve the outcomes of methotrexate while minimizing both renal and non-renal toxicity. Both honey (H) and olive oil (OO) are bioactive substances widely used as nutraceuticals that exhibited a potent therapeutic and antioxidant properties. This study aimed to assess the possible protective effect of H and OO intake either singly or together against the biochemical and structural Methotrexate-induced nephrotoxicity in rats. The study was conducted on 56 adult albino rats, they were divided into seven groups (n = 8): group 1 received only distelled water (negative control), group 2 received H (1.2 g/kg/day), group 3 received OO (1.25 ml/kg/day), group 4 received a single intraperitoneal injection of MTX (20 mg/kg), group 5 received MTX and H, group 6 received MTX and OO, group 7 received MTX, H and OO together. At the end of the experiment (2 weeks), all rats were sacrificed, and blood samples were assessed for kidney function tests. Kidney tissues were evaluated for several antioxidant parameters including Malondialdehyde (MDA), Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. Tissues were also processed for histological and immunohistochemical assessments. Results revealed that both H and OO improved the kidney function markers, histopathological and immunohistological changes due to Methotrexate-induced renal damage. Additionally, both substances also redeemed the oxidative damage of the kidney by decreasing MDA and increasing anti-oxidant enzymatic activities. Such effects were more apparent when the two substances were given together. Ultimately, our results proof that H and OO amiolerate the Methotrexate-induced nephrotoxicity in rats, thus they can be used as an adjuvant supplements for patients requiring methotrexate therapy.

Evaluation of the time-dependent osteogenic activity of glycerol incorporated magnesium oxide nanoparticles in induced calvarial defects.

Introduction: Magnesium-based biomaterials have been explored for their potential as bone healing materials, as a result of their outstanding biodegradability and biocompatibility. These characteristics make magnesium oxide nanoparticles (MgO NPs) a promising material for treating bone disorders. The purpose of this investigation is to assess the osteogenic activity of newly-developed locally administered glycerol-incorporated MgO NPs (GIMgO NPs) in rabbits' calvarial defects. Materials and methods: Characterization of GIMgO was done by X-ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). Bilateral calvarial defects were created in eighteen New Zealand Rabbits, of which they were divided into 3 groups with time points corresponding to 2, 4, and 6 weeks postoperatively (n = 6). One defect was implanted with absorbable gel foam impregnated with GIMgO NPs while the other was implanted with gel foam soaked with glycerol (the control). The defects were assessed using histological, Micro-Computed Tomography (Micro-CT), and histometric evaluation. Results: The characterization of the GIMgO nanogel revealed the presence of MgO NPs and glycerol as well as the formation of the crystalline phase of the MgO NPs within the nanogel sample. The histological and micro-CT analysis showed time-dependent improvement of healing activity in the calvarial defects implanted with GIMgO NPs when compared to the control. Furthermore, the histometric analysis demonstrated a marked increase in the total area of new bone, connective tissue, new bone area and volume in the GIMgO NPs implanted site. Statistically, the amount of new bone formation was more significant at 6 weeks than at 2 and 4 weeks postoperatively in the calvarial defects implanted with GIMgO NPs as compared to the control. Conclusion: The locally applied GIMgO NPs demonstrated efficacy in promoting bone formation, with more significant effects observed over an extended period. These findings suggest its suitability for clinical use as a therapeutic alternative to enhance bone healing.

The Impact of Chronic Unpredictable Mild Stress-Induced Depression on Spatial, Recognition and Reference Memory Tasks in Mice: Behavioral and Histological Study.

Depression-induced cognitive impairment has recently been given more attention in research. However, the relationship between depression and different types of memory is still not clear. Chronic unpredictable mild stress (CUMS) is a commonly used animal model of depression in which animals are exposed to chronic unpredictable environmental and psychological stressors, which mimics daily human life stressors. This study investigated the impact of different durations of CUMS on various types of memory (short- and long-term spatial memory and recognition memory) and investigated CUMS' impact on the ultrastructural level by histological assessment of the hippocampus and prefrontal cortex. Twenty male C57BL/J6 mice (6 weeks old, 21.8 ± 2 g) were randomly divided into two groups (n = 10): control and CUMS (8 weeks). A series of behavioral tasks were conducted twice at weeks 5-6 (early CUMS) and weeks 7-8 (late CUMS). A tail-suspension test (TST), forced swimming test (FST), elevated zero maze (EZM), elevated plus maze (EPM), open field test (OFT), and sucrose-preference test (SPT) were used to assess anxiety and depressive symptoms. The cognitive function was assessed by the novel object recognition test (NORT; for recognition memory), Y-maze (for short-term spatial memory), and Morris water maze (MWM: for long-term spatial memory) with a probe test (for reference memory). Our data showed that 8 weeks of CUMS increased the anxiety level, reported by a significant increase in anxiety index in both EPM and EZM and a significant decrease in central preference in OFT, and depression was reported by a significant increase in immobility in the TST and FST and sucrose preference in the SPT. Investigating the impact of CUMS on various types of memory, we found that reference memory is the first memory to be affected in early CUMS. In late CUMS, all types of memory were impaired, and this was consistent with the abnormal histological features of the memory-related areas in the brain (hippocampus and prefrontal cortex).

Assessment of the dose-dependent biochemical and cytotoxicity of zein-coated MgO nanowires in male and female albino rats.

Introduction: Recently, zein-coated MgO nanowires were synthesized, which could be promising as an effective antimicrobial compounds that can be combined in the preparation of a diversity of new dental formulations. However, there is a deficiency of information concerning their toxicological profile regarding the human health.Objective: This in vivo study aimed to explore the hepato- and nephrotoxicity of low versus high doses of zein-coated MgO nanowires in rats.Materials and Methods: A 21-day recurrent dose toxicity research was carried out. Wistar rats were divided into 2 main groups, males and females (n = 18). Each group was further subdivided into 3 subgroups: control, MgO-zein nanowires low dose, MgO-zein nanowires high dose. The low dose used was 100 mg/kg while the high dose used was 200 mg/kg.Results: The results showed that MgO-zein nanowires at both doses did not affect the electrolytes levels compared to the control levels. Also, they did not produce any significant alteration in liver function markers in both rats' genders. MgO-zein nanowires at both doses did not produce any effective alteration in serum creatinine in treated rats of both genders. Moreover, very minimal histological alterations were observed in both doses of MgO-zein nanowires in liver and kidney of both genders.Conclusion: Based on the observed safety of zein-coated MgO nanowires, it can be utilized as an effective antimicrobial compound that can be combined in the preparation of a diversity of new dental formulations.KEY MESSAGESMgO NPs are globally used in multiple fields including the therapeutic field.Zein has wide pharmaceutical applications especially coating the tablet over sugar.There are no cytotoxic studies that investigate MgO-zein nanowires safety until now.

In vitro Investigation of the Antimicrobial Activity of Mouth Washes Incorporating Zein-Coated Magnesium Oxide Nanoparticles.

PURPOSE: This in vitro study was undertaken to investigate the antimicrobial effect of distinctive oral mouth washes after the addition of zein-coated (Magnesium oxide) MgO nanoparticles on exemplary of some oral microorganisms. MATERIALS AND METHODS: Three hundred and twelve samples were used in this study. A set of five concentrations of MgO nanoparticles with zein and without zein-coating were incorporated into three oral mouth washes: Listerine zero, Listerine total control and Oral B in the mass percentages of 0.3%, 0.5%, 1%, 2%, 5% and 10%, in addition to controls with no MgO nanoparticles. The antimicrobial effect of three mouth washes with variable concentrations of MgO was tested against the following organisms: Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis and Candida albicans using the disc diffusion test (DDT) and direct contact test (DCT). Data were analyzed using one-way ANOVA statistical test. RESULTS: The tested mouthwashes with zein-coated MgO nanoparticles showed significant differences of antimicrobial activity on S. mutans, S. aureus, E. faecalis, and C. albicans in the disc diffusion test. While in the DCT, all tested mouthwashes with MgO nanoparticles with and without zein coating showed antimicrobial activity on all tested microorganisms. CONCLUSION: Zein-coated MgO nanoparticles may be considered as a potential antimicrobial agent when added to oral mouthwashes. Future analysis, including in vivo studies, is required in order to incorporate zein/MgO nanoparticles into oral mouthwashes that may improve its antibacterial property.

Thymoquinone ameliorates oxidative damage and histopathological changes of developing brain neurotoxicity.

Lead (Pb) toxicity is known to be a chief environmental health issue, especially for pregnant women and young children. Today, the use of medicinal herbs in the treatment of many diseases and different toxic agents has become highly accepted due to their effectiveness and lower costs. Thymoquinone (TQ), which is extracted from Nigella sativa seeds, is a potent antioxidant and anti-inflammatory agent. This study was designed to explore the optional protectivity of TQ against maternal and fetal oxidative stress and brain damage induced by Pb administration. Pregnant rats were distributed into seven groups: control group, TQ group, DMSO group, two groups Pb-treated (160 and 320 ppm), and two groups Pb-treated (160 and 320 ppm) co-treated with TQ. Administration started from gestation day 1 (GD1) to day 20 (GD20) through oral gavage once daily. Lead administration caused a dose-dependent toxicity for both mothers and fetuses. Also, the histopathological assessment of the brains from Pb-treated groups showed marked alterations. Co-treatment of with TQ and Pb caused a significant decrease in Pb levels as compared with those treated with Pb alone and amelioration of histopathological changes in the brains. It was concluded that co-treatment of TQ along with gestational Pb exposure could mitigate the effects against Pb-induced maternal and fetal neurotoxicity.

Morphohistometric study of the ligamentum flavum in cervical, thoracic and lumbar vertebrae: comparative approach

Anatomic characterization and fine structure of the human ligamentum flavum (LF), especially at different spinal levels, represent an attractive focus for the scientific and surgical application. Descriptive anatomical and structural study of LF at the cervical, thoracic and lumbar levels of the vertebral column in human cadavers is carried out here. The aim of the work is to clarify the anatomical features and fine structural differences in the human LF at different vertebral levels (cervical, thoracic and lumbar). Specimens of vertebral column were obtained from 34 human preserved cadavers. Their average age ranged between 56 and 69 years. Morphometric parameters including height, width and thickness of the ligament flavum at the midlevels of cervical, thoracic and lumbar regions were measured. Sections obtained from different levels were stained with different stains. Morphometric measurements involved the relative elastic area, relative collagen area, elastic area and collagen area% were measured.The results of the height, width and thickness of the LF at different spinal levels showed gradual increase in their mean values respectively. The LF midline gaps were found in the cervical, thoracic and lumbar regions. The morphometrical measurements showed that the average elastic area was highest in the cervical region and lowest in the thoracic region. In the lumbar region, the percentages of both elastic area and the collagen area were nearly the same. The characterization of morphological and histological aspects of the LF at different spinal levels will be of great importance for applications in spinal surgery, biomechanical and physical rehabilitation of vertebral column

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Analytical study of clinicopathological data of Saudi patients with osteoarthritis subjected to total knee arthroplasty / Estudio analítico de datos clínico-patológicos de pacientes sauditas con osteoartritis sometidos a artroplastia total de rodilla

Knee osteoarthritis (OA) is a common disabling disease. Epidemiological studies have revealed various risk factors for OA, including sex, aging, obesity, occupational illnesses, and chronic diseases. Here we evaluate the clinical, pathological, and radiological findings of knee OA in a subset of Saudi patients who were subjected to total knee replacement (TKA). The study population included 30 Saudi patients with knee OA who were operated by TKA (from June 2014 to December 2015) in the Department of Orthopedics, Faculty of Medicine, King Abdulaziz University, Saudi Arabia. Patient's clinical and radiological data were collected from the hospital files. Pathological examination of the excised superior articular surface of tibia and femoral condyles were done. Pearson Chi-squared analysis was used to test for differences between the variables in associated risk factors. There were more women than men. Sixty per cent of patients were older than 60 years [mean age, 59.2 (females) and 61.7 (men) years-old]. All patients exceeded obesity class 1, with females being more obese than males. Pathological examination of the superior articular surface of tibia and femoral condyles showed high score lesions, which was more apparent in females than in males. Radiological findings showed that most lesions were high grade. The findings of this study will help to understand the pathogenesis of OA and improve treatment decision making relevant to TKA in knee OA in Saudi Arabia and elsewhere.

La artrosis de rodilla (OA, por sus siglas en inglés) es una enfermedad invalidante común. Los estudios epidemiológicos han revelado diversos factores de riesgo para la OA, que incluyen el sexo, el envejecimiento, la obesidad, las enfermedades profesionales y las enfermedades crónicas. Aquí evaluamos los hallazgos clínicos, patológicos y radiológicos de la OA de rodilla en un subconjunto de pacientes sauditas que fueron sometidos a reemplazo total de rodilla (RTR). La población de estudio incluyó a 30 pacientes saudíes con OA de rodilla que fueron operados por RTR (desde junio de 2014 hasta diciembre de 2015) en el Departamento de Ortopedia, Facultad de Medicina, King Abdulaziz University, Arabia Saudita. Los datos clínicos y radiológicos de los pacientes se obtuvieron de las fichas hospitalarias. Se realizó examen patológico de la superficie articular superior de la tibia extirpada y cóndilos femorales. Se utilizó el análisis Chi-cuadrado de Pearson para probar las diferencias entre las variables en los factores de riesgo asociados. El número de mujeres era mayor que los hombres. El 60 % de los pacientes eran mayores de 60 años [edad media, 59,2 (mujeres) y 61,7 (hombres) años]. Todos los pacientes superaron la obesidad clase 1, siendo las mujeres más obesas que los hombres. El examen patológico de la superficie articular superior de la tibia y los cóndilos femorales mostraron lesiones con puntaje alto, que fue más evidente en mujeres que en hombres. Los hallazgos radiológicos mostraron que la mayoría de las lesiones eran de alto grado. Los hallazgos de este estudio ayudarán a comprender la patogenia de la OA y mejorarán la toma de decisiones sobre el tratamiento relevante para el RTR en la OA de rodilla en Arabia Saudita y en otros lugares.

The combined effect of honey and olive oil against methotrexate mediated hepatotoxicity in rats: A biochemical, histological and immunohistological study.

BACKGROUND: Honey and olive oil are natural products that have high nutritional values, and therapeutic properties. Cytotoxic drugs, like methotrexate (MTX) are used to treat malignancies in tumour cells; however, these drugs also have serious side effects that could threaten the patient's life. AIM: To evaluate the potential protective effects of honey and olive oil, administered alone or together, against MTX-induced hepatotoxicity in rats. METHODS: Adult male albino rats were divided: Group I: negative control (n=8); II: honey ( daily by oral 1.2 g/kg bwt (n=8), III: olive oil (1 ml/day)(n=8), IV: single intraperitoneal injection of MTX (20 mg/kg bwt)(n=8), V: diluted honey for 3 days before injection of MTX (n=8), Group VI: olive oil for 3 days before injection of MTX (n=8), Group VII: both honey and olive oil for 3 days before injection of MTX (n=8). After treatment, rats were sacrified and blood samples were collected to determine liver function parameters, liver tissue used to measure the oxidative (malondialdehyde), antioxidative parameters (superoxide dismutase, catalase and glutathione peroxidase), histological and immunohistochemical techniques. RESULTS: The administration of honey and olive oil exerted a protective effect against MTX-induced hepatotoxicity, as demonstrated by the normalization of the liver enzymes, proteins and total bilirubin and by the histopathological and immunohistological changes observed in the livers. Both agents also reversed the oxidative damage in the liver by decreasing level of MDA levels and increasing the antioxidant related by enzymes in the liver homogenates compared to the control rats. These effects were more evident when the two agents were administered together. CONCLUSION: The combined intake of honey and olive oil could be hepatoprotective. Co-administration of these agents might form an effective adjuvant therapy and minimize side effects of chemoherapy in cancerous patients.

2-Methoxyestradiol Attenuates Testosterone-Induced Benign Prostate Hyperplasia in Rats through Inhibition of HIF-1α/TGF-ß/Smad2 Axis.

Benign prostatic hyperplasia (BPH) is a common disorder in the male population. 2-Methoxyestradiol (2ME) is an end metabolite of estrogens with pleiotropic pharmacological properties. This study aimed to explore the potential ameliorative effects of 2ME against testosterone-induced BPH in rats. 2-Methoxyestradiol (50 and 100 mg/kg, dissolved in DMSO) prevented the rise in prostatic index and weight in comparison to testosterone-alone-treated animals for 2 weeks. Histological examination indicated that 2ME ameliorated pathological changes in prostate architecture. This was confirmed by the ability of 2ME to decrease the glandular epithelial height when compared to the testosterone group. Also, 2ME improved testosterone-induced oxidative stress as it inhibited the rise in lipid peroxide content and the exhaustion of superoxide dismutase (SOD) activity. The beneficial effects of 2ME against the development of BPH were substantiated by assessing proliferation markers, preventing the rise in cyclin D1 protein expression and enhancing Bax/Bcl2 mRNA ratio. It significantly reduced prostate content of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), nuclear factor κB (NF-κB), and transforming growth factor ß (TGF-ß). In addition, 2ME reduced hypoxia-inducible factor 1-α (HIF-1α) and phospho-Smad2 (p-Smad2) protein expression compared to the testosterone group. In conclusion, 2ME attenuates experimentally induced BPH by testosterone in rats through, at least partly, inhibition of HIF-1α/TGF-ß/Smad2 axis.

The prenatal toxic effect of methylmercury on the development of the appendicular skeleton of rat fetuses and the protective role of vitamin E.

Methylmercury (MeHg) is an environmental contaminant that is found in many ecosystems. Many studies reported that MeHg toxicity is accompanied by increased lipid peroxidation that may lead to oxidative damage to DNA, RNA, and proteins. Vitamin E is considered as the most effective antioxidant preventing lipid peroxidation. The aim of this study was to evaluate the effects of MeHg exposure during pregnancy on the development of the appendicular skeleton in rat fetuses and whether vitamin E administration could reduce this toxicity. Positively mated adult female Sprague-Dawley rats were used and divided into the following experimental groups: control group, received only deionized water, and four MeHg treated groups received 1 mg of MeHg/kg/d, 2 mg of MeHg/kg/d, 1 mg of MeHg/kg/d plus 150 mg of vitamin E/kg/d, and 2 mg of MeHg/kg/d, plus 150 mg of vitamin E/kg/d starting from Day 0 of gestation. On Day 20 of gestation, the fetuses from the pregnant rats were extracted and the fetal growth parameters were evaluated. Skeletal evaluation of ossification of both fore- and hind-limbs, and coxal bones were undertaken. Results showed that treatment with MeHg caused adverse effects on fetal growth parameters and ossification of the bones. The coadministration of vitamin E with MeHg revealed an improvement in these parameters. These results suggest that vitamin E may ameliorate some aspects of MeHg developmental toxicity. The underlying and human health implications warrant further investigations.