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Lead Toxicity
Published in Debasis Bagchi, Manashi Bagchi, Metal Toxicology Handbook, 2020
Rokeya Pervin, Md. Akil Hossain, Dipti Debnath, Mohiuddin Ahmed Bhuiyan
The hematopoietic system is directly affected by lead through the prevention of hemoglobin synthesis as a result of hindering several vital enzymes that are responsible for heme synthesis. In addition, by decreasing the strength of the cell membrane, lead minimizes the lifetime of circulating erythrocytes. The collective consequence of these two actions leads to anemia [57]. Anemia caused on account of lead poisoning can be of two types: hemolytic anemia, which is associated with acute high-level lead exposure, and frank anemia, which is caused only when the blood lead level is significantly elevated for prolonged periods [58]. Lead significantly affects the heme synthesis pathway in a dose-dependent manner by downregulating the three key enzymes, such as aminolevulinic acid synthetase (ALAS), δ-aminolevulinic acid dehydratase (ALAD), and ferrochelatase which are involved in the synthesis of heme [59]. Lead hinders these three fundamental enzymes of this pathway; however, the impact of lead on ALAD is extremely severe, and the level of lead toxicity is measured clinically by the degree of ALAD inhibition [17]. In addition, ALAS inhibition could be responsible for liver toxicity. Therefore, the production of heme is blocked by the combined inhibition of these three enzymes through the heme synthesis pathway [17]. The mechanisms involved in the reduction of the life span of erythrocytes are not yet sufficiently revealed.
Microneedles: Current Trends and Applications
Published in Tuhin S. Santra, Microfluidics and Bio-MEMS, 2020
Hima Manoj, Pallavi Gupta, Loganathan Mohan, Moeto Nagai, Syrpailyne Wankhar, Tuhin S. Santra
Low-molecular-weight drugs are administered using microneedle pretreatment of the skin to increase its permeability. As drugs for systemic indications generally require high doses, initial studies involving this approach were performed for the delivery of small marker compounds, that is, calcein (molecular weight 623 Da) [11], galanthamine (molecular weight 287 Da) [84], and docetaxel in elastic liposomes [85]. Pretreatment with microneedles followed by drug application was used for the delivery of naltrexone across guinea pig and human skin. Microneedle patches were used for drug delivery to human subjects, and the subjects showed elevated and prolonged naltrexone plasma levels for 3 days after microneedle application [86]. Microneedle patches were also employed in topical photodynamic therapy using 5-aminolevulinic acid or 5-aminolevulinic acid methyl ester delivery through skin [87]. The production of the photosensitizer protoporphyrin IX was measured to be higher after delivery of the drug combined with skin pretreatment using a microneedle both in humans and rats. This approach was also used for successfully delivering the preformed photosensitizer meso-tetra(N-methyl-4-pyridyl) porphinetetratosy-late [88].
Toxicology of Air Pollution
Published in Lorris G. Cockerham, Barbara S. Shane, Basic Environmental Toxicology, 2019
Donald E. Gardner, Susan C. M. Gardner
Toxicity Profile. The toxicity of lead is due to its ability to bind to biologically important molecules, disrupting physiological functions. Hematological, neurological, and renal effects have been associated with lead toxicity at low lead exposures. Lead toxicity is due in part to depletion of heme because of the direct inhibition of delta-aminolevulinic acid dehydratase and other enzymes involved in heme biosynthesis (Dresner et al., 1982). The resulting anemia is due to a shortening of erythrocyte survival time. Neurological effects have been demonstrated at blood lead levels as low as 40 to 60 µg/dl in adults and may be responsible for altered behavior and decreases in IQ (Lilis et al., 1977; Irwig et al., 1978; Hammond et al., 1980). Morphological changes in renal mitochondria are an early response to lead exposure (Goyer and Rhyne, 1973). Lead induced nephropathy has been seen in humans at blood levels between 40 and 100 µg/dl. Reproductive and developmental processes can also be adversely affected by lead exposures (Lane, 1949). Lead is readily transferred across the placenta and in rodent studies fetotoxicity has occurred at a concentration of 10 µg/m3 (U.S. EPA, 1986). Epidemiologic studies indicate that fetal exposure to lead may have undesirable effects on mental development of the newborn and the length of the gestation period. In the male, lead may have an adverse effect on the development of sperm and the seminal vesicles.
Evaluation of environmental effects of heavy metals on biochemical profile and oxidative stress among children at brick kiln sites
Published in Archives of Environmental & Occupational Health, 2021
Mehwish David, Naheed Turi, Qurat-ul Ain, Humaira Rahman, Sarwat Jahan
Kamal et al. (2015) have shown in their respective study, that exposure to brick kiln emitted PAH affect the hematological parameters in blood such as serum c-reactive proteins (CRP), WBCs, Hb, RBC, and PLT counts.27 The present study reported similar results, where we observed that children living at brick kiln sites experience decreased concentrations of RBCs and Hb level in blood due to exposure to heavy metals. The current findings are in accordance with the previous work of Jahan et al.9 where decrease in RBCs number and Hb was evident among brick kiln male workers, whose blood was found to contain higher concentration of heavy metals (Cd, Cr, Ni).9 Heavy metals are known to inhibit heme and hemoglobin production by decreasing the activity of δ-aminolevulinic acid dehydratase (ALAD), which is a cytosolic sulfhydryl enzyme that convert ALA into porphobilinogen.28 Higher concentration of ALA and decrease in prophobilinogen levels causes generation of reactive oxygen species, which disrupt RBCs morphology and survival.28 The levels of MCH, MCHC, HCT and Hb were slightly decreased in present study that might be due to oxidative stress caused by metals, leading to alteration in RBCs morphology and ultimately, decreasing level of Hb as previously suggested by Zhao et al.29
Changes in biochemical composition and fatty acid accumulation of Nannochloropsis oculata in response to different iron concentrations
Published in Biofuels, 2021
Soheila Sabzi, Mehdi Shamsaie Mehrgan, Houman Rajabi Islami, Seyed Pezhman Hosseini Shekarabi
It has been demonstrated that manipulation of different medium components and cultivation conditions influence biochemical composition of microalgae for the synthesis of preferred products. Several components of culture medium such as nitrogen, phosphorous, iron, zinc, copper, sulfur and cobalt are known to serve as cofactors in a variety of metabolic pathways essential for microalgae growth and lipid production [11,14,17,28]. Fe is quantitatively the most important micronutrient required for the survival and growth of all photosynthetic organisms [29]. At cellular level, there is requirement of Fe in catalytic activities due to its redox properties and involvement in photosynthetic and respiratory electron transport system [30], hydrogen photo-production [31], nitrate and nitrogen assimilation [32]. Fe is also required in the biosynthesis of major photosynthetic pigments such as chlorophyll and phycocyanin by affecting their precursor fixation like δ-aminolevulinic acid [33]. Because of low solubility in aerobic conditions, Fe supplementation could enhance algal growth by improving its bioavailability to photoautotrophic cells. Accordingly, low Fe concentration generally leads to a decrease in the cellular light harvest [34], which can influence microalgae growth.
Environmental exposure to lead and hematological parameters in Afro-Brazilian children living near artisanal glazed pottery workshops
Published in Journal of Environmental Science and Health, Part A, 2020
Homegnon A. F. Bah, Matheus J. Bandeira, Erival A. Gomes-Junior, Ana Laura S. Anjos, Ynayara J. M. Rodrigues, Nathália R. dos Santos, Victor O. Martinez, Rômula B. M. A. Rocha, Renata G. Costa, Elisângela V. Adorno, José A. Menezes-Filho
Blood lead (PbB) level analysis indicates recent exposure and is considered a gold standard for the evaluation of human exposure, despite the fact of being an invasive approach. In addition, blood offers the possibility to evaluate the hematological effects by assessing the δ-aminolevulinic acid dehydratase (ALA-D) enzyme activity and its reactivation index (ALAD-RE).[10] ALA-D is a metallo-enzyme involved in the heme biosynthesis pathway that catalyzes the condensation of two δ-aminolevulinic acid (ALA) molecules for porphobilinogen (PBG) formation. Reagents such as dithiothreitol (DTT) or zinc chloride (ZnCl2) cancel the inhibition of ALAD produced by Pb, allowing ALAD reactivation and the evaluation of Pb toxicity to the red blood cells.[10,11]