The protective effect of curcumin on the diabetic rat kidney: A stereological, electron microscopic and immunohistochemical study.

The prevalence of diabetes in the world is increasing rapidly. Kidney diseases are among the most common medical disorders. The aim of this study was to investigate the effect of curcumin on the diabetic kidney. Thirty-five female Wistar albino rats were divided into seven groups. No procedure was performed on the Cont group. The Sham group received corn oil via gavage for 14 days. The curcumin (Curc) group received 30-mg/kg curcumin for 14 days, while the diabetes mellitus (DM) group received 50-mg/kg streptozotocin (STZ) in a single dose intraperitoneally. The DM + curcumin 1 (DC1) group received 30 mg/kg curcumin for 14 days, seven days after the application of STZ, while the DM + curcumin 2 (DC2) received 30 mg/kg curcumin for 14 days, 21 days after the application of STZ, and the DM + curcumin 3 (DC3) group received single-dose STZ at the same time as the application of 30 mg/kg curcumin for 14 days. Medulla, cortex, tubule, and glomerulus volume ratios were calculated using stereological techniques. Cortex volumes in the Sham and DM groups were significantly lower than in the Cont group (p < 0.05). The cortex volume in the DC3 group was also significantly lower than in the Curc group (p < 0.05). Medullary volume was significantly higher in the DC3 group compared to the DM group (p < 0.05). Curcumin was determined to exhibit a protective effect on the diabetic kidney since the glomerulus in the curcumin-exposed group exhibited a well-protected structure following experimentally induced diabetes based on light and electron microscopic analysis findings. These findings suggest that curcumin used following experimentally induced diabetes exhibits protective effects on the diabetic kidney.

A concise review of optical, physical and isotropic fractionator techniques in neuroscience studies, including recent developments.

Stereology is a collection of methods which makes it possible to produce interpretations about actual three-dimensional features of objects based on data obtained from their two-dimensional sections or images. Quantitative morphological studies of the central nervous system have undergone significant development. In particular, new approaches known as design-based methods have been successfully applied to neuromorphological research. The morphology of macroscopic and microscopic structures, numbers of cells in organs and structures, and geometrical features such as length, volume, surface area and volume components of the organ concerned can be estimated in an unbiased manner using stereological techniques. The most practical and simplest stereological method is the fractionator technique, one of the most widely used methods for total particle number estimation. This review summarizes fractionator methods in theory and in practice. The most important feature of the methods is the simplicity of its application and underlying reasoning. Although there are three different types of the fractionator method, physical, optical and isotropic (biochemical), the logic underlying its applications remains the same. The fractionator method is one of the strongest and best options among available methods for estimation of the total number of cells in a given structure or organ. The second part of this review focuses on recent developments in stereology, including how to deal with lost caps, with tissue section deformation and shrinkage, and discusses issues of calibration, particle identification, and the role of stereology in the era of a non-histological alternative to counting of cells, the isotropic fractionator (brain soup technique).

Effects of mobile phone exposure on metabolomics in the male and female reproductive systems.

With current advances in technology, a number of epidemiological and experimental studies have reported a broad range of adverse effects of electromagnetic fields (EMF) on human health. Multiple cellular mechanisms have been proposed as direct causes or contributors to these biological effects. EMF-induced alterations in cellular levels can activate voltage-gated calcium channels and lead to the formation of free radicals, protein misfolding and DNA damage. Because rapidly dividing germ cells go through meiosis and mitosis, they are more sensitive to EMF in contrast to other slower-growing cell types. In this review, possible mechanistic pathways of the effects of EMF exposure on fertilization, oogenesis and spermatogenesis are discussed. In addition, the present review also evaluates metabolomic effects of GSM-modulated EMFs on the male and female reproductive systems in recent human and animal studies. In this context, experimental and epidemiological studies which examine the impact of mobile phone radiation on the processes of oogenesis and spermatogenesis are examined in line with current approaches.

The genomic effects of cell phone exposure on the reproductive system.

Humans are exposed to increasing levels of electromagnetic fields (EMF) at various frequencies as technology advances. In this context, improving understanding of the biological effects of EMF remains an important, high priority issue. Although a number of studies in this issue and elsewhere have focused on the mechanisms of the oxidative stress caused by EMF, the precise understanding of the processes involved remains to be elucidated. Due to unclear results among the studies, the issue of EMF exposure in the literature should be evaluated at the genomic level on the reproductive system. Based on this requirement, a detail review of recently published studies is necessary. The main objectives of this study are to show differences between negative and positive effect of EMF on the reproductive system of animal and human. Extensive review of literature has been made based on well known data bases like Web of Science, PubMed, MEDLINE, Google Scholar, Science Direct, Scopus. This paper reviews the current literature and is intended to contribute to a better understanding of the genotoxic effects of EMF emitted from mobile phones and wireless systems on the human reproductive system, especially on fertility. The current literature reveals that mobile phones can affect cellular functions via non-thermal effects. Although the cellular targets of global system for mobile communications (GSM)-modulated EMF are associated with the cell membrane, the subject is still controversial. Studies regarding the genotoxic effects of EMF have generally focused on DNA damage. Possible mechanisms are related to ROS formation due to oxidative stress. EMF increases ROS production by enhancing the activity of nicotinamide adenine dinucleotide (NADH) oxidase in the cell membrane. Further detailed studies are needed to elucidate DNA damage mechanisms and apoptotic pathways during oogenesis and spermatogenesis in germ cells exposed to EMF.

A brief update on physical and optical disector applications and sectioning-staining methods in neuroscience.

A quantitative description of a three-dimensional (3D) object based on two-dimensional images can be made using stereological methods These methods involve unbiased approaches and provide reliable results with quantitative data. The quantitative morphology of the nervous system has been thoroughly researched in this context. In particular, various novel methods such as design-based stereological approaches have been applied in neuoromorphological studies. The main foundations of these methods are systematic random sampling and a 3D approach to structures such as tissues and organs. One key point in these methods is that selected samples should represent the entire structure. Quantification of neurons, i.e. particles, is important for revealing degrees of neurodegeneration and regeneration in an organ or system. One of the most crucial morphometric parameters in biological studies is thus the "number". The disector counting method introduced by Sterio in 1984 is an efficient and reliable solution for particle number estimation. In order to obtain precise results by means of stereological analysis, counting items should be seen clearly in the tissue. If an item in the tissue cannot be seen, these cannot be analyzed even using unbiased stereological techniques. Staining and sectioning processes therefore play a critical role in stereological analysis. The purpose of this review is to evaluate current neuroscientific studies using optical and physical disector counting methods and to discuss their definitions and methodological characteristics. Although the efficiency of the optical disector method in light microscopic studies has been revealed in recent years, the physical disector method is more easily performed in electron microscopic studies. Also, we offered to readers summaries of some common basic staining and sectioning methods, which can be used for stereological techniques in this review.

Genotoxic and carcinogenic effects of non-ionizing electromagnetic fields.

New technologies in electronics and communications are continually emerging. An increasing use of these electronic devices such as mobile phone, computer, wireless fidelity connectors or cellular towers is raising questions concerning whether they have an adverse effect on the body. Exposure to electromagnetic fields (EMF) is frequently suggested to have adverse health effects on humans and other organisms. This idea has been reported in many studies. In contrast, the therapeutic effects of EMF on different organs have also been reported. Research findings are inconsistent. This has given rise to very profound discrepancies. The duration and frequency of mobile phone calls and the association observed with various health effects has raised serious concerns due to the frequency with which these devices are used and the way they are held close to the head. The present review assesses the results of in vitro, in vivo, experimental, and epidemiological studies. The purpose of the study is to assess data concerning the carcinogenic and genotoxic effects of non-ionizing EMF. The major genotoxic and carcinogenic effects of EMF, divided into subsections as low frequency effects and radiofrequency effects, were reviewed. The inconsistent results between similar studies and the same research groups have made it very difficult to make any comprehensive interpretation. However, evaluation of current studies suggests that EMF may represent a serious source of concern and may be hazardous to living organisms.

The use of non-steroidal anti-inflammatory drugs in neurological diseases.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been in use for many years and constitute a large part of prescriptions issued in daily practice. Although NSAIDs are used for many diseases in neurology, they have also been tested as a new therapeutic option for various other diseases. While their effects on headache and cerebrovascular diseases are well known, little is known about their impact on neurodegenerative diseases. This review discusses the use, effects and safety of NSAIDs in neurological diseases.

Peripheral nerve and diclofenac sodium: Molecular and clinical approaches.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed medications worldwide. Diclofenac sodium (DS), one of these NSAIDs, has a high specificity for arachidonic acid-degrading cyclooxygenase (COX)-2 enzymes. This drug can be used to relieve neuropathic pain. In this review, we examine the relevant researches, including in vivo, animal, and clinical human studies, with the aim of understanding the effect of DS on the peripheral nerves. In injured nerves, COX-2 is potently upregulated around the injury site. When a nerve is damaged, both COX-1 and COX-2 expression is increased in macrophages and Schwann cells. In addition, COX inhibitors can promote axonal outgrowth in cultured neurons. Neuropathic pain occurs after injury and leads to dysfunction of the peripheral nervous system. NSAIDs can modulate the nociceptive and inflammatory pain pathways and control neuropathic pain. DS may accelerate nerve regeneration and its effects on healing, as well as causing deleterious effects in the developing nerves. DS teratogenicity disrupts myelin sheath thickness and axon structure. Understanding the possible benefits and limitations of DS and specific conditions such as prenatal use will be of benefit in clinical practice.

The use of diclofenac sodium in urological practice: A structural and neurochemical based review.

Diclofenac sodium (DS) is a non-steroidal anti-inflammatory drug with antipyretic and analgesic effects. It is mainly found in the form of sodium salt. The mechanism of action of DS operates by way of cyclooxygenase (COX) inhibition. The physiological effect of this substance derives from a decrease in prostaglandin production. DS is a benzeneacetic acid derivative with anti-inflammatory properties. As a non-steroidal anti-inflammatory drug (NSAID), DS binds to both forms of COX (COX-1 and COX-2) and inhibits the conversion of arachidonic acid into pro-inflammatory prostaglandins by means of chelation. At the same time, this agent is also able to inhibit tumor angiogenesis, in which COX-2 is involved. DS is effective in overcoming pain and inflammation when it inhibits COX-2, but gastrointestinal side effects appear when it inhibits COX-1. In this review, we have focused on chemical structure and pharmacokinetic properties and renal effects of DS in light of current knowledge. Additionally, use of diclofenac nanoparticles were also discussed.

As a painkiller: a review of pre- and postnatal non-steroidal anti-inflammatory drug exposure effects on the nervous systems.

Diclofenac sodium (DS) is commonly used for the treatment of acute and chronic pain, even for extended periods of time. Over the years, DS has been associated with toxicity in nervous tissue, in addition to its anti-inflammatory properties. Basic neurobiological research has enhanced our understanding of the biological and pathological outcomes of toxicity. Several studies have suggested DS-induced cytotoxicity in the nervous system. Prenatal toxicities of DS are thought to be capable of leading to postnatal defects. This review describes the morphoquantitative, histological and pathological effects of DS on the central and peripheral nervous systems. Knowledge of these effects may assist with the development of a suitable therapeutic approach. In addition, understanding the mechanism of DS-dependent neuronal impairments may contribute to selection of appropriate antioxidant therapy.

The neuroprotective effect of melatonin on the hippocampus exposed to diclofenac sodium during the prenatal period.

Melatonin (Mel) has strong antioxidant properties since it is a direct scavenger of oxygen-based free radicals and related species. The main aim of this study is to show whether the effects of Mel can prevent the potential adverse effects of diclofenac sodium (DS), used as a non-steroidal anti-inflammatory drug (NSAID) during the prenatal period, on the newborn experimental rat brain tissues using stereological methods Twenty-four male 12-week old Wistar albino rats were used. The study involved four groups (each containing six rats), those exposed, during the prenatal period, to saline 1ml/kg (Saline group), to diclofenac sodium 3.6mg/kg (DS group), or to diclofenac sodium+melatonin 50mg/kg (DS+Mel group), and a control group (Cont group). At the end of the experiment, the brains were removed from the cranium for histological and stereological analyses. Cell loss in the hippocampus exposed to DS was observed compared to the Cont group (p<0.01), and a similar side-effect was also seen in the Saline group (p<0.01). However, there was no significant difference in cell numbers between the Cont and DS+Mel groups (p>0.05). These results suggest that exposure to DS during pregnancy causes a decrease in the number of cells in the hippocampus and dentate gyrus in the postnatal period. Using Mel, a neuroprotective agent, reduced the toxic effects of DS.

Prenatal exposure to low-dose diclofenac sodium does not affect total neuron numbers in spinal segment T13 in rats.

The main purpose of the present study was to investigate the effects of diclofenac sodium (DS) on the total number of neurons in segment T13 of the spinal cord of offspring of pregnant rats using stereological methods. Eighteen adult female Wistar albino rats weighing 150-200g were used. Pregnant female rats were divided into three groups; a control group, a sham group and a DS (1mg/kg, intramuscular) exposed group. The DS and sham groups received injection from the 5th day of gestation to the 19th. Twenty eight days after birth, the offspring rats were perfused with 4% buffered formalin. T13, which is one of transverse spinal cord segments, were isolated and processed for routine paraffin histology. 5µm sections were obtained using a rotary microtome according to systematic random sampling strategies. Every 40th section was taken and sections were stained with modified Giemsa. All types of motor neuron cell were identified according to their morphology. In this study, the "disector-Cavalieri combination" method was used in the stereological examination of neurons. The motor neurons were counted in the right gray matter of the ventral horn in the spinal cord segment. The Kruskal-Wallis test was used for comparison the groups. In terms of motoneuron number, no significant difference among the groups was found (p>0.05). In conclusion, our results indicated that prenatal exposure to DS has no effect on the total number of motor neuron of the offspring rats.

Skeptical approaches concerning the effect of exposure to electromagnetic fields on brain hormones and enzyme activities.

This review discusses the effects of various frequencies of electromagnetic fields (EMF) on brain hormones and enzyme activity. In this context, the mechanism underlying the effects of EMF exposure on tissues generally and cellular pathway specifically has been discussed. The cell membrane plays important roles in mediating enzymatic activities as to response and reacts with extracellular environment. Alterations in the calcium signaling pathways in the cell membrane are activated in response to the effects of EMF exposure. Experimental and epidemiological studies have demonstrated that no changes occur in serum prolactin levels in humans following short-term exposure to 900 Mega Hertz (MHz) EMF emitted by mobile phones. The effects of EMF on melatonin and its metabolite, 6-sulfatoxymelatonin, in humans have also been investigated in the clinical studies to show a disturbance in metabolic activity of melatonin. In addition, although 900 MHz EMF effects on NF-κB inflammation, its effects on NF-κB are not clear. Abbreviations: ELF-EMF, extremely low frequency electromagnetic fields; EMF, electromagnetic fields; RF, Radiofrequency; ROS, reactive oxygen species; VGCCs, voltage-gated calcium channels; MAPK, mitogen-activated phosphokinase; NF-κB, nuclear factor kappa B; ERK-1/2, extracellular signal-regulated kinase; GSH-Px, glutathione peroxidase; JNK, Jun N-terminal kinases; SOD, superoxide dismutase; MnSOD, manganese-dependent superoxide dismutase; GLUT1, glucose transporter 1; GSSG-Rd, glutathione reductase MDA malondialdehyde; NO, nitric oxide; LH, luteinizing hormone; FSH, follicle-stimulating hormone.

Does omega-3 have a protective effect on the rat adrenal gland exposed to 900 MHz electromagnetic fields?

The aim of this study was to investigate the harmful effects of exposure to 900-megahertz (MHz) electromagnetic fields (EMF) and the protective effects of omega-3 (Omg-3) against EMF in the rat adrenal gland. Eighteen Wistar albino rats were randomly assigned into three groups, control (Cont), EMF, and EMF + Omg-3. The EMF and EMF + Omg-3 groups both consisted of six rats exposed to an EMF of 900 MHz for 60 min/day for 15 days. No procedure was applied to the six rats in the Cont group. At the end of the experiment, all rats were sacrificed, and the mean volumes of the cortex and medulla of the adrenal gland were estimated using a stereological counting technique. The stereological results showed that the mean volume of the adrenal gland increased significantly in the EMF-exposed groups compared to the Cont group. Additionally, the mean volume of the adrenal gland was significantly lower in the EMF + Omg-3 group compared to the EMF group. We suggest that Omg-3 therapy aimed at suppressing the effects of EMF may prove a safe alternative for animals, whether or not they are exposed to EMF.

Effects of short and long term electromagnetic fields exposure on the human hippocampus.

The increasing use of mobile phones may have a number of physiological and psychological effects on human health. Many animal and human studies have reported various effects on the central nervous system and cognitive performance from of exposure to electromagnetic fields (EMF) emitted by mobile phones. The aim of the present study was to evaluate the effects of mobile phones on the morphology of the human brain and on cognitive performance using stereological and spectroscopic methods and neurocognitive tests. Sixty healthy female medical school students aged 18-25 years were divided into a low exposure group (30 subjects, <30 min daily use by the head) and high exposure group (30 subjects, >90 min daily use by the head). Magnetic resonance images (MRI) of the brain analysed on OsiriX 3.2.1 workstation. Neuropsychological tests were performed for each subject. In addition, three dominant specific metabolites were analysed, choline at 3.21 ppm, creatine at 3.04 ppm and N-acetyl aspartate at 2.02 ppm. Analysis of the spectroscopic results revealed no significant difference in specific metabolites between the groups (p > 0.05). There was also no significant difference in terms of hippocampal volume between the groups (p > 0.05). In contrast, the results of the stroop and digit span (backward) neurocognitive tests of high exposure group for evaluating attention were significantly poorer from low exposure group (p < 0.05). Based on these results, we conclude that a lack of attention and concentration may occur in subjects who talk on mobile phones for longer times, compared to those who use phones relatively less.

Effects of electromagnetic fields exposure on the antioxidant defense system.

Technological devices have become essential components of daily life. However, their deleterious effects on the body, particularly on the nervous system, are well known. Electromagnetic fields (EMF) have various chemical effects, including causing deterioration in large molecules in cells and imbalance in ionic equilibrium. Despite being essential for life, oxygen molecules can lead to the generation of hazardous by-products, known as reactive oxygen species (ROS), during biological reactions. These reactive oxygen species can damage cellular components such as proteins, lipids and DNA. Antioxidant defense systems exist in order to keep free radical formation under control and to prevent their harmful effects on the biological system. Free radical formation can take place in various ways, including ultraviolet light, drugs, lipid oxidation, immunological reactions, radiation, stress, smoking, alcohol and biochemical redox reactions. Oxidative stress occurs if the antioxidant defense system is unable to prevent the harmful effects of free radicals. Several studies have reported that exposure to EMF results in oxidative stress in many tissues of the body. Exposure to EMF is known to increase free radical concentrations and traceability and can affect the radical couple recombination. The purpose of this review was to highlight the impact of oxidative stress on antioxidant systems. Abbreviations: EMF, electromagnetic fields; RF, radiofrequency; ROS, reactive oxygen species; GSH, glutathione; GPx, glutathione peroxidase; GR, glutathione reductase; GST, glutathione S-transferase; CAT, catalase; SOD, superoxide dismutase; HSP, heat shock protein; EMF/RFR, electromagnetic frequency and radiofrequency exposures; ELF-EMFs, exposure to extremely low frequency; MEL, melatonin; FA, folic acid; MDA, malondialdehyde.

Effects of 900-MHz radiation on the hippocampus and cerebellum of adult rats and attenuation of such effects by folic acid and Boswellia sacra.

The radiation emitted from mobile phones has various deleterious effects on human health. This study was conducted to evaluate the effects of exposure to the 900-MHz radiation electromagnetic fields (EMF) emitted by mobile phones on Ammon's horn and the dentate gyrus (DG) in the hippocampus and cerebellum of male Wistar albino rats. We also investigated the neuroprotective effects of the antioxidants Boswellia sacra (BS) and folic acid (FA) against exposure to EMF. Twenty-four adult male rats were randomly divided into four groups of six animals each, an EMF group, an EMF + FA exposure group (EFA), an EMF + BS exposure group (EBS) and a control group (Cont). The EMF, EFA and EBS groups were exposed to 900-MHz EMF radiation inside a tube once daily over 21 days (60 min/day). The Cont group was not exposed to 900-MHz EMF. The results showed that EMF caused a significant decrease in total pyramidal and granular cell numbers in the hippocampus, and DG and in Purkinje cell numbers in the cerebellum in the EMF group compared to the other groups (p < 0.05). BS and FA attenuated the neurodegenerative effects of EMF in the hippocampus and cerebellum. Significant differences were also determined between the numbers of neurons in the EFA and EMF groups, and between the EBS and EMF groups (p < 0.05). However, there were no significant differences among Cont, EFA and EBS (p > 0.05). Our results may contribute to ongoing research into the effects of 900-MHz EMF exposure. Abbreviations: BS, Boswellia sacra; CA, cornu ammonis; CAT, catalase; CE, coefficient of error; CV, coefficient of variation; DG, dentate gyrus; DNA, deoxyribonucleic acid; EMF, electromagnetic field; EBS, the group that is exposed to EMF and received a single daily gavage of BS (500 mg/kg/day) during 21 days; EEG, electroencephalogram; EFA, the group that is exposed to EMF and received a single daily gavage of folic acid (50 mg/kg/day) during 21 days; FA, folic acid; gr, granular layer; H2O2, hydrogen peroxide; MHz, Megahertz; ml, molecular layer; RF, radiofrequency; ROS, reactive oxygen specimens; SEM, standard error of the mean.

Electromagnetic field and brain development.

Rapid advances in technology involve increased exposures to radio-frequency/microwave radiation from mobile phones and other wireless transmitting devices. As cell phones are held close to the head during talking and often stored next to the reproductive organs, studies are mostly focused on the brain. In fact, more research is especially needed to investigate electromagnetic field (EMF)'s effects on the central nervous system (CNS). Several studies clearly demonstrate that EMF emitted by cell phones could affect a range of body systems and functions. Recent work has demonstrated that EMF inhibit the formation and differentiation of neural stem cells during embryonic development and also affect reproductive and neurological health of adults that have undergone prenatal exposure. The aim of this review is to discuss the developing CNS and explain potential impacts of EMF on this system.