Ecogenetics of lead toxicity and its influence on risk assessment

Mani, Monica Shirley; Kabekkodu, Shama Prasada; Joshi, Manjunath B.; Dsouza, Herman Sunil

doi:10.1177/0960327119851253

Cited by 37 publications

(15 citation statements)

References 228 publications

(298 reference statements)

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“…Lead can promptly affect the dynamism of epigenetic determinants and promote the rapid turnover of DNA methylation [4]. Consistent with these findings and statements, lead is known to be an epigenetic modifier [53]. The following are advances of three main epigenetic systems associated with lead neurotoxicity:…”

Section: Lead-induced Epigenetic Alterations In Cnsmentioning

confidence: 52%

Epigenetics and Lead Neurotoxicity

Xu¹,

Zhang²

2020

Lead Chemistry

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Lead exposure continues to threaten human health in a worldwide perspective. Among the multiple target organs affected by lead, central nervous system (CNS) pervades in the adverse consequences by chronic lead exposure, leading to a variety of neurotoxic manifestations and neurological disorders. The epigenetic machinery plays a vital role in the control of key neural functions, particularly neuronal development. Faulty epigenetic gene regulation can have marked deleterious effect on the developing brain that can last for an entire lifespan. Mounting evidence suggests that lead exposure can pose detrimental effect on CNS through these epigenetic mechanisms. And this chapter reviews the current understandings of concrete epigenetic forms, exemplified by DNA methylation, histone modification, and ncRNAs, responding to lead exposure and moderating the consequent neurotoxicity. In addition, Alzheimer's disease (AD) is presented as a typical instance to explain how environmental lead exposure results in the occurrence of AD in an "early exposure, late onset" fashion. A future perspective, highlighting additional forms of epigenetic elements as well as interactive actions among different molecules, was also proposed. In summary, epigenetics was substantially implicated in regulating lead neurotoxicity.

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Section: Lead-induced Epigenetic Alterations In Cnsmentioning

confidence: 52%

Epigenetics and Lead Neurotoxicity

Xu¹,

Zhang²

2020

Lead Chemistry

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“…Furthermore, chronic Pb-exposure and chronic Pb-poisoning are associated with deleterious systemic effects, including the nervous system, cardiovascular, hemopoietic, renal, reproductive, skeletal, and gastrointestinal 38 , 39 . The mechanism of the effect of Pb-toxicity on dysfunction in different organs is reported due to displacement of divalent metal ions 40 , oxidative damage 41 , inhibition of thiol groups in proteins 42 , inhibition of enzymes in heme biosynthesis pathway 43 , and epigenetic modifications 44 .…”

Section: Discussionmentioning

confidence: 99%

Association between Musculoskeletal Pain and Bone Turnover Markers in Long-Term Pb-Exposed Workers

2021

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Background: On chronic exposure, Lead (Pb) deposits in the skeletal system, replaces calcium ions, and alters the normal physiological processes, which in turn, lead to stunting, delayed fracture healing, and high resorption of collagen molecules. The present study aimed to assess the association of musculoskeletal pain and discomfort with bone turnover markers (BTMs) among long-term Pb-exposed workers. Study design: A cross-sectional study. Methods: The study recruited 176 male Pb-exposed workers and 80 control subjects who were matched for age, gender, and socio-economic status. Blood lead levels (BLLs), bone growth markers, such as serum osteocalcin (OC), alkaline phosphatase (ALP), bone alkaline phosphatase (BAP), and bone resorption markers: serum pyridinoline (Pry), deoxypyridinoline (DPry), tartrate-resistant acid phosphatase-5b(TRACP-5b), and hydroxyproline in urine (HyP-U) of participants were investigated. Pain and discomfort in the musculoskeletal system were assessed using Nordic Musculoskeletal Questionnaire. Results: Pb-exposure was significantly associated with musculoskeletal discomfort of the lower back (P<0.001), upper back (P<0.001), and ankle/foot (P=0.011). Among bone formation markers, serum OC was significantly lower in musculoskeletal discomfort of elbows (P=0.033) and ankle/foot (P=0.042). Among bone resorption markers, serum DPry was significantly lower in musculoskeletal discomfort of the neck (P=0.049) and shoulders (P=0.023). HyP-U was significantly higher in musculoskeletal discomfort of shoulders (P=0.035) and lower back (P=0.036). Conclusion: As evidenced by the obtained results, Pb-exposure was associated with musculoskeletal discomfort of the lower back, upper back, and ankle/foot. Lower bone formation (serum OC) marker was noted with musculoskeletal discomfort of elbows and ankle/foot. Furthermore, bone resorption markers were associated with musculoskeletal discomfort of the neck, shoulders, and lower back. The findings of the present study suggested that long-term Pb-exposure and BTMs were associated with musculoskeletal discomfort.

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“…Lead is known as an epigenetic modifier [92], with its association to neural epigenetic reprogramming long established. Chronic lead exposure results in various epigenetic changes, characterized by DNA methylation [93], histone modification [94] and ncRNAs [95].…”

Section: Lead Exposure and Epigeneticsmentioning

confidence: 99%

Epigenetic Basis of Lead-Induced Neurological Disorders

Wang

Zhang

2020

IJERPH

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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.

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Ecogenetics of lead toxicity and its influence on risk assessment

Cited by 37 publications

References 228 publications

Epigenetics and Lead Neurotoxicity

Epigenetics and Lead Neurotoxicity

Association between Musculoskeletal Pain and Bone Turnover Markers in Long-Term Pb-Exposed Workers

Epigenetic Basis of Lead-Induced Neurological Disorders

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