Disrupted Sleep Homeostasis and Altered Expressions of Clock Genes in Rats with Chronic Lead Exposure

Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep–wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague–Dawley rats with chronic lead exposure consumed drinking water that contained 250 ppm of lead acetate for five weeks. Electroencephalography and electromyography were recorded for scoring the architecture of the sleep–wake cycle in animals. At six Zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22), three clock genes, including rPer1, rPer2, and rBmal1b, were analyzed. The rats with chronic lead exposure showed decreased slow wave sleep and increased wakefulness in the whole light period (ZT1 to ZT12) and the early dark period (ZT13 to ZT15) that was followed with a rebound of rapid-eye-movement sleep at the end of the dark period (ZT22 to ZT24). The disturbance of the sleep–wake cycle was associated with changes in clock gene expression that was characterized by the upregulation of rPer1 and rPer2 and the feedback repression of rBmal1b. We concluded that chronic lead exposure has a negative impact on the sleep–wake cycle in rats that predominantly disrupts sleep homeostasis. The disruption of sleep homeostasis was associated with a toxic effect of lead on the clock gene expression in the hypothalamus.

Chronic Lead Exposure Alters Mineral Properties in Alveolar Bone

The objective of the present study was to investigate the effects of chronic lead exposure on the mineral properties of alveolar bone. For this purpose, female Wistar rats (n = 8) were exposed to 1000 ppm lead acetate in drinking water for 90 days, while the control group (n = 5) was treated with sodium acetate. The alveolar bone structure and chemical composition of the dissected mandibles were examined using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), inductively coupled plasma optical emission spectrometry (ICP-OES), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and X-ray diffraction (XRD) techniques to determine possible alterations in alveolar bone due to lead exposure. In addition, changes in bone mechanical properties were analysed using a three-point bending test. Exposure to lead induced notable changes in bone mineralization and properties, specifically a reduction of the trabecular thickness and bone mineral density. Furthermore, there was a reduction in carbonate content and an increase in bone mineral crystallinity. These changes in bone mineralization could be explained by an alteration in bone turnover due to lead exposure. Three-point bending showed a trend of decreased displacement at failure in the mandibles of lead-exposed rats, which could compromise the mechanical stability and normal development of the dentition.

Liver Function Tests in Mine Workers Exposed to Lead: An Occupational Cohort Study

Background: Operational processes in lead mines cause workers to be occupationally exposed to lead particles, chronic exposure to lead can results innumerous health effects.Method: To know the effects of chronic lead exposure on liver function, the blood lead levels (BLL) and liver function tests of lead miners for 3- years (2017-2019) were followed and the obtained results were compared with those attained in the non-exposed group.Results: The BLL levels of the lead-mine workers were higher than with recommended level and the non-exposed group (24.15 and 6.35 µg dL-1, respectively, p<0.001). The findings indicated a positive and significant relationship between BLL and lactate dehydrogenase (r: 0.942, p<0.001), aspartate transaminase (r: 0.869, p<0.001), alkaline phosphatase (r: 0.9679, p<0.005), alanine transaminase (r: 0.9779, p<0.001), and bilirubin (r: 0.9169, p<0.001) levels, while we found a negative and significant correlation between BLL and triglyceride (r: -0.929, p<0.05), total protein (r: -0.896, p<0.001), albumin (r: -0.941, p<0.0021), and globulin (r: -0.863, p<0.001) levels. Moreover, no significant relationship was found between BLL and cholesterol, LDL, LDH, and BUN levels (p>0.05).Conclusions: This report showed that the chronic lead exposure is a major occupational hazard in lead mine workers. Despite the fact that the level of liver function parameters was in the normal range, the results of 3- years follow-up show a significant relationship between BLL and alteration of liver function parameters levels of lead miners. The study can be helpful in raising awareness of alteration in liver functions due to occupational exposure to lead.

AMERLIORATIVE EFFECT OF CINNAMALDEHYDE AGAINST LEAD ACETATE INDUCED SPLENIC TOXICITY OF SWISS ALBINO MICE (MUS MUSCULUS)

Our mother India is full of various herbal plants with great medicinal importance. Cinnamaldehyde, an active component of Cinnamon, one of the widely used spice has antifungal, anti-microbial, anti-oxidative and many other properties. Our present study is aimed to investigate the ameliorative effect of Cinnamaldehyde upon the splenic toxicity induced by chronic lead exposure. For this lead acetate was applied on female Swiss albino mice (Mus musculus) continuously for 120 days. After treatment with lead, only selective dose of Cinnamaldehyde was applied on the mice for last 30 days. For observing the hazardous effects of this heavy metal and curative effect of Cinnamaldehyde, we explored various biological parameters like TBARS, GSH along with morphometric and histo-pathological analysis. Our observations clearly depicted the dose-dependent ill effects of this toxic heavy metal. Post –treatment of Cinnamaldehyde at a selective dose helped the tissue to get rid of this toxicity at certain level. All these findings disclosed the ameliorative effects of Cinnamaldehyde upon lead toxicity on spleen.

Epigenetic Basis of Lead-Induced Neurological Disorders

Environmental lead (Pb) exposure is closely associated with pathogenesis of a range of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), attention deficit/hyperactivity disorder (ADHD), etc. Epigenetic machinery modulates neural development and activities, while faulty epigenetic regulation contributes to the diverse forms of CNS (central nervous system) abnormalities and diseases. As a potent epigenetic modifier, lead is thought to cause neurological disorders through modulating epigenetic mechanisms. Specifically, increasing evidence linked aberrant DNA methylations, histone modifications as well as ncRNAs (non-coding RNAs) with AD cases, among which circRNA (circular RNA) stands out as a new and promising field for association studies. In 23-year-old primates with developmental lead treatment, Zawia group discovered a variety of epigenetic changes relating to AD pathogenesis. This is a direct evidence implicating epigenetic basis in lead-induced AD animals with an entire lifespan. Additionally, some epigenetic molecules associated with AD etiology were also known to respond to chronic lead exposure in comparable disease models, indicating potentially interlaced mechanisms with respect to the studied neurotoxic and pathological events. Of note, epigenetic molecules acted via globally or selectively influencing the expression of disease-related genes. Compared to AD, the association of lead exposure with other neurological disorders were primarily supported by epidemiological survey, with fewer reports connecting epigenetic regulators with lead-induced pathogenesis. Some pharmaceuticals, such as HDAC (histone deacetylase) inhibitors and DNA methylation inhibitors, were developed to deal with CNS disease by targeting epigenetic components. Still, understandings are insufficient regarding the cause–consequence relations of epigenetic factors and neurological illness. Therefore, clear evidence should be provided in future investigations to address detailed roles of novel epigenetic factors in lead-induced neurological disorders, and efforts of developing specific epigenetic therapeutics should be appraised.