Health Time

Nimbolide epigenetically regulates autophagy and apoptosis in breast cancer.

PMID:

Toxicol In Vitro. 2018 Sep ;51:114-128. Epub 2018 May 17. PMID: 29778718

Abstract Title:

Nimbolide epigenetically regulates autophagy and apoptosis in breast cancer.

Abstract:

Autophagy is a critical regulator of cellular homeostasis and its dysregulation often results in various disease manifestations, including cancer. Nimbolide, an active chemical constituent of neem (Azadirachta indica) exhibits potent anticancer effects. Although, nimbolide mediated apoptosis activation in breast cancer cells is well known. Nevertheless, its role in autophagy induction mechanism and epigenetic alteration is not explored previously. Our current study intended to bridge the gaps in the existing research by exploring the potential of nimbolide in inducing autophagy, which could counter regulate the transformations in breast cancer. In our studies, nimbolide significantly inhibited the cell proliferation of MDA-MB-231 and MCF-7 cells with ICvalues of 1.97 ± 0.24 and 5.04 ± 0.25 μM, respectively. Nimbolide markedly arrested the cell cycle progression and cell survival with loss of mitochondrial membrane potential by reducing Bcl-2 concomitantly inducing Bax and caspases protein expression with modulation of HDAC-2 and H3K27Ac expression.Consequently, characteristic autophagolysosome accumulation was observed by acridine orange, monodansylcadaverine (MDC) and Lysotracker Red staining. Moreover, nimbolide induced autophagy signaling by increasing Beclin 1 and LC3B along with decreased p62 and mTOR protein expression. Thus, our findings imply that nimbolide induces autophagy mediated apoptotic cell death in breast cancer with epigenetic modifications.

Mobile phone radiation exposure increases oxidative stress as evidenced by increased protein carbonyl and malondialdehyde, coupled with impaired cognition.

PMID:

Indian J Biochem Biophys. 2013 Apr ;50(2):114-9. PMID: 23720885

Abstract Title:

Effect of low level microwave radiation exposure on cognitive function and oxidative stress in rats.

Abstract:

Use of wireless communicating devices is increasing at an exponential rate in present time and is raising serious concerns about possible adverse effects of microwave (MW) radiation emitted from these devices on human health. The present study aimed to evaluate the effects of 900 MHz MW radiation exposure on cognitive function and oxidative stress in blood of Fischer rats. Animals were divided into two groups (6 animals/group): Group I (MW-exposed) and Group II (Sham-exposed). Animals were subjected to MW exposure (Frequency 900 MHz; specific absorption rate 8.4738 x 10(-5) W/kg) in Gigahertz transverse electromagnetic cell (GTEM) for 30 days (2 h/day, 5 days/week). Subsequently, cognitive function and oxidative stress parameters were examined for each group. Results showed significant impairment in cognitive function and increase in oxidative stress, as evidenced by the increase in levels of MDA (a marker of lipid peroxidation) and protein carbonyl (a marker of protein oxidation) and unaltered GSH content in blood. Thus, the study demonstrated that low level MW radiation had significant effect on cognitive function and was also capable of leading to oxidative stress.

Mobile phone radiation leads to cytotoxic and genotoxic damage in both immature and mature rats, with rate of damage being statistically higher in immature rats.

PMID:

Int J Radiat Biol. 2013 Nov ;89(11):985-92. Epub 2013 Jun 21. PMID: 23718180

Abstract Title:

Evaluation of the cytogenotoxic damage in immature and mature rats exposed to 900 MHz radiofrequency electromagnetic fields.

Abstract:

PURPOSE: One of the most important issues regarding radiofrequency electromagnetic fields (RF-EMF) is their effect on genetic material. Therefore, we investigated the cytogenotoxic effects of 900 MHz radiofrequency electromagnetic fields (RF-EMF) and the effect of a recovery period after exposure to RF-EMF on bone marrow cells of immature and mature rats.MATERIALS AND METHODS: The immature and mature rats in treatment groups were exposed to RF-EMF for 2 h/day for 45 days. Average electrical field values for immature and mature rats were 28.1± 4.8 V/m and 20.0 ± 3.2 V/m, respectively. Whole-body specific absorption rate (SAR) values for immature and mature rats were in the range of 0.38-0.78 W/kg, and 0.31-0.52 W/kg during the 45 days, respectively. Two recovery groups were kept for 15 days after RF-EMF exposure.RESULTS: Significant differences were observed in chromosome aberrations (CA), micronucleus (MN) frequency, mitotic index (MI) and ratio of polychromatic erythrocytes (PCE) in all treatment and recovery groups. The cytogenotoxic damage in immature rats was statistically higher than the mature rats. The recovery period did not reduce the damage to the same extent as the corresponding control groups.CONCLUSIONS: The exposure of RF-EMF leads to cytotoxic and genotoxic damage in immature and mature rats. More sensitive studies are required to elucidate the possible carcinogenic risk of EMF exposure in humans, especially children.

2.1 GHz microwave radiation decreases cell viability, reduces mitochondrial membrane potential, and results in cell death in breast fibroblast cells in vitro.

PMID:

Cell Biochem Biophys. 2013 ;67(3):1371-8. PMID: 23723005

Abstract Title:

Investigation of the effects of 2.1 GHz microwave radiation on mitochondrial membrane potential (ΔΨm), apoptotic activity and cell viability in human breast fibroblast cells.

Abstract:

In the present study we aimed to investigate the effects of 2.1 GHz Wideband Code Division Multiple Access (W-CDMA) modulated Microwave (MW) Radiation on cell survival and apoptotic activity of human breast fibroblast cells. The cell cultures were exposed to W-CDMA modulated MW at 2.1 GHz at a SAR level of 0.607 W/kg for 4 and 24 h. The cell viability was assessed by MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. The percentage of apoptotic cells was analyzed by Annexin V-FITC and PI staining. 5,5',6,6'-Tetrachloro-1,1',3,3'- tetraethylbenzimidazolcarbocyanine iodide (JC-1) was used to measure Mitochondrial Membrane Potential (ΔΨm). sFasL and Fas/APO-1 protein levels were determined by ELISA method. 2.1 GHz MW radiation was shown to be able to inhibit cell proliferation and induce apoptosis in human breast fibroblast cells. The cell viability of MW-exposed cells was decreased significantly. The percentages of Annexin V-FITC positive cells were higher in MW groups. ΔΨm was decreased significantly due to MW radiation exposure. However, neither sFas nor FasL level was significantly changed in MW-exposed fibroblast cells. The results of this study showed that 2.1 GHz W-CDMA modulated MW radiation-induced apoptotic cell death via the mitochondrial pathway.

Male rats exposed to 1800 MHz electromagnetic fields exhibit circadian alterations including lowered sperm count and motility.

PMID:

Chronobiol Int. 2014 Feb ;31(1):123-33. Epub 2013 Oct 11. PMID: 24117058

Abstract Title:

Circadian alterations of reproductive functional markers in male rats exposed to 1800 MHz radiofrequency field.

Abstract:

In this study, we explored the circadian effects of daily radiofrequency field (RF) exposure on reproductive functional markers in adult male Sprague-Dawley rats. Animals in circadian rhythm (as indicated by melatonin measurements), were divided into several groups and exposed to 1800 MHz RF at 205 μw/cm(2) power density (specific absorption rate 0.0405 W/kg) for 2 h/day for 32 days at different zeitgeber time (ZT) points, namely, ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20. Sham-exposed animals were used as controls in the study. From each rat, testicular and epididymis tissues were collected and assessed for testosterone levels, daily sperm production and sperm motility, testis marker enzymes γ-GT and ACP, cytochrome P450 side-chain cleavage (p450cc) mRNA expression, and steroidogenic acute regulatory protein (StAR) mRNA expression. Via these measurements, we confirmed the existence of circadian rhythms in sham-exposed animals. However, rats exposed to RF exhibited a disruption of circadian rhythms, decreased testosterone levels, lower daily sperm production and sperm motility, down-regulated activity of γ-GT and ACP, as well as altered mRNA expression of cytochrome P450 and StAR. All of these observations were more pronounced when rats were exposed to RF at ZT0. Thus, our findings indicate potential adverse effects of RF exposure on male reproductive functional markers, in terms of both the daily overall levels as well as the circadian rhythmicity.

Dose-dependent DNA damage resulting from mobile phone radiation is attentuated by pretreatment with melatonin in vitro.

PMID:

Int J Radiat Biol. 2013 Nov ;89(11):993-1001. Epub 2013 Sep 3. PMID: 23952262

Abstract Title:

Mobile phone radiation induces mode-dependent DNA damage in a mouse spermatocyte-derived cell line: a protective role of melatonin.

Abstract:

PURPOSE: To evaluate whether exposure to mobile phone radiation (MPR) can induce DNA damage in male germ cells.MATERIALS AND METHODS: A mouse spermatocyte-derived GC-2 cell line was exposed to a commercial mobile phone handset once every 20 min in standby, listen, dialed or dialing modes for 24 h. DNA damage was determined using an alkaline comet assay.RESULTS: The levels of DNA damage were significantly increased following exposure to MPR in the listen, dialed and dialing modes. Moreover, there were significantly higher increases in the dialed and dialing modes than in the listen mode. Interestingly, these results were consistent with the radiation intensities of these modes. However, the DNA damage effects of MPR in the dialing mode were efficiently attenuated by melatonin pretreatment.CONCLUSIONS: These results regarding mode-dependent DNA damage have important implications for the safety of inappropriate mobile phone use by males of reproductive age and also suggest a simple preventive measure: Keeping mobile phones as far away from our body as possible, not only during conversations but during 'dialed' and 'dialing' operation modes. Since the 'dialed' mode is actually part of the standby mode, mobile phones should be kept at a safe distance from our body even during standby operation. Furthermore, the protective role of melatonin suggests that it may be a promising pharmacological candidate for preventing mobile phone use-related reproductive impairments.

Mobile phone electromagnetic field exposure influences cognitive processes in rats.

PMID:

Behav Brain Res. 2014 Jan 1 ;258:80-9. Epub 2013 Oct 18. PMID: 24144546

Abstract Title:

Spatial learning, monoamines and oxidative stress in rats exposed to 900 MHz electromagnetic field in combination with iron overload.

Abstract:

The increasing use of mobile phone technology over the last decade raises concerns about the impact of high frequency electromagnetic fields (EMF) on health. More recently, a link between EMF, iron overload in the brain and neurodegenerative disorders including Parkinson's and Alzheimer's diseases has been suggested. Co-exposure to EMF and brain iron overload may have a greater impact on brain tissues and cognitive processes than each treatment by itself. To examine this hypothesis, Long-Evans rats submitted to 900 MHz exposure or combined 900 MHz EMF and iron overload treatments were tested in various spatial learning tasks (navigation task in the Morris water maze, working memory task in the radial-arm maze, and object exploration task involving spatial and non spatial processing). Biogenic monoamines and metabolites (dopamine, serotonin) and oxidative stress were measured. Rats exposed to EMF were impaired in the object exploration task but not in the navigation and working memory tasks. They also showed alterations of monoamine content in several brain areas but mainly in the hippocampus. Rats that received combined treatment did not show greater behavioral and neurochemical deficits than EMF-exposed rats. None of the two treatments produced global oxidative stress. These results show that there is an impact of EMF on the brain and cognitive processes but this impact is revealed only in a task exploiting spontaneous exploratory activity. In contrast, there are no synergistic effects between EMF and a high content of iron in the brain.

Rats born to mothers exposed to mobile phone radiation exhibit altered electrophysiological properties of CA1 pyramidal neurons, deleteriously impacting cognition.

PMID:

Toxicol Ind Health. 2016 Jun ;32(6):968-79. Epub 2014 Mar 6. PMID: 24604340

Abstract Title:

Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

Abstract:

Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques.

Mobile phone exposure induces oxidative stress in the brain, kidneys, and liver and also increases liver enzyme activity.

PMID:

Electromagn Biol Med. 2015 ;34(4):279-84. Epub 2014 Apr 8. PMID: 24712749

Abstract Title:

Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

Abstract:

Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levelsin brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p

Microscopic analyses reveal cochlear apoptosis and necrosis associated with exposure to both 900 MHz and 1800 MHz electromagnetic fields in rats.

PMID:

J Laryngol Otol. 2014 May ;128(5):400-5. Epub 2014 May 1. PMID: 24784924

Abstract Title:

The effect of radiofrequency radiation generated by a Global System for Mobile Communications source on cochlear development in a rat model.

Abstract:

OBJECTIVE: This study aimed to determine the effect of radiofrequency radiation generated by 900 and 1800 MHz Global System for Mobile Communications sources on cochlear development in the rat model.METHODS: Eight pregnant albino Wistar rats were divided into three groups: control, 900 MHz and 1800 MHz. The latter two groups of pregnant rats were exposed to radiofrequency radiation for 1 hour per day starting on the 12th day of pregnancy until delivery. The rats in the control, 900 MHz and 1800 MHz groups gave birth to 24, 31 and 26 newborn rats respectively. Newborn rats in the 900 MHz and 1800 MHz groups were exposed to radiofrequency radiation for 1 hour per day for 21 days after delivery. Hearing evaluations of newborn rats were carried out using distortion product otoacoustic emissions testing. Eight newborn rats were randomly selected from each group for electron microscopic evaluation.RESULTS: Distortion product otoacoustic emission tests revealed no significant difference among the groups, but electron microscopic evaluation revealed significant differences among the groups with regard to the number of normal, apoptotic and necrotic cells.CONCLUSION: The findings indicated cellular structural damage in the cochlea caused by radiofrequency radiation exposure during cochlear development in the rat model.