Human Erythrocyte Acetylcholinesterase in Health and Disease

Saldanha, Carlota

doi:10.3390/molecules22091499

Cited by 57 publications

(35 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Alternatively, it could be an indication that AChE/Hb is a suboptimal exposure metric in the study population. AChE can be influenced by many physiological and pathological conditions, 37 including blood sugar levels. For example, patients with dysregulated type 1 diabetes have been shown to have lower AChE activity than both healthy controls and well-controlled type 1 diabetics.…”

Section: Workplacementioning

confidence: 99%

Exposure to cholinesterase inhibiting insecticides and blood glucose level in a population of Ugandan smallholder farmers

et al. 2020

View full text Add to dashboard Cite

ObjectivesThe risk of diabetes mellitus may be elevated among persons exposed to some pesticides, including cholinesterase-inhibiting insecticides (organophosphates and carbamates). The objective of this study was to investigate how acetylcholinesterase activity was associated with mean blood glucose levels among smallholder farmers in Uganda.MethodsWe conducted a short-term follow-up study among 364 smallholder farmers in Uganda. Participants were examined three times from September 2018 to February 2019. At each visit, we measured glycosylated haemoglobin A (HbA1c) as a measure of long-term average blood glucose levels. Exposure to organophosphate and carbamate insecticides was quantified using erythrocyte acetylcholinesterase normalised by haemoglobin (AChE/Hb). For a subgroup of participants, fasting plasma glucose (FPG) was also available. We analysed HbA1c and FPG versus AChE/Hb in linear mixed and fixed effect models adjusting for age, sex, physical activity level, and consumption of fruits and vegetables, alcohol and tobacco.ResultsContrary to our hypothesis, our mixed effect models showed significant correlation between low AChE/Hb and low HbA1c. Adjusted mean HbA1c was 0.74 (95% CI 0.17 to 1.31) mmol/mol lower for subjects with AChE/Hb=24.3 U/g (35th percentile) compared with subjects with AChE/Hb=25.8 U/g (50th percentile). Similar results were demonstrated for FPG. Fixed effect models showed less clear correlations for between-phase changes in AChE/Hb and HbA1c.ConclusionsOur results do not clearly support a causal link between exposure to cholinesterase-inhibiting insecticides and elevated blood glucose levels (expressed as HbA1c and FPG), but results should be interpreted with caution due to the risk of reverse causality.

show abstract

Section: Workplacementioning

confidence: 99%

Exposure to cholinesterase inhibiting insecticides and blood glucose level in a population of Ugandan smallholder farmers

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Hence, erythrocyte rigidity represents an important factor affecting oxygen delivery to the tissues, since oxygen-carrying capacity decreases when erythrocytes become more rigid. In this way, increased red blood cell rigidity results in an impaired peripheral perfusion and, finally, tissue oxygenation [18]. As an integral membrane protein, B3p, in addition to gas exchange across the cell membrane, is also involved in erythrocyte mechanical and osmotic properties, such as docking of glycolytic enzymes and maintenance of cell shape [19].…”

Section: Role In Erythrocyte Rigiditymentioning

confidence: 99%

Natural Antioxidants Beneficial Effects on Anion Exchange through Band 3 Protein in Human Erythrocytes

Morabito¹,

Marino²

2019

Antioxidants

View full text Add to dashboard Cite

Band 3 protein (B3p) exchanging Cl− and HCO3− through erythrocyte membranes is responsible for acid balance, ion distribution and gas exchange, thus accounting for homeostasis of both erythrocytes and entire organisms. Moreover, since B3p cross links with the cytoskeleton and the proteins underlying the erythrocyte membrane, its function also impacts cell shape and deformability, essential to adaptation of erythrocyte size to capillaries for pulmonary circulation. As growing attention has been directed toward this protein in recent years, the present review was conceived to report the most recent knowledge regarding B3p, with specific regard to its anion exchange capability under in vitro oxidative conditions. Most importantly, the role of natural antioxidants, i.e., curcumin, melatonin and Mg2+, in preventing detrimental oxidant effects on B3p is considered.

show abstract

“…AChE is also inhibited by pharmaceutical carbamates like rivastigmine, which is used in the treatment of Alzheimer’s disease (Pinho et al 2013 ). Besides its importance for the nervous system, AChE is also present in the blood, where it is involved in the nitric oxide signal pathway (Saldanha 2017 ). As measuring human AChE activity in the nervous system is difficult, red-blood cell AChE activity is often taken as a surrogate biomarker for AChE activity in the nervous system.…”

Section: Introductionmentioning

confidence: 99%

Acetylcholinesterase inhibition in electric eel and human donor blood: an in vitro approach to investigate interspecies differences and human variability in toxicodynamics

et al. 2020

View full text Add to dashboard Cite

In chemical risk assessment, default uncertainty factors are used to account for interspecies and interindividual differences, and differences in toxicokinetics and toxicodynamics herein. However, these default factors come with little scientific support. Therefore, our aim was to develop an in vitro method, using acetylcholinesterase (AChE) inhibition as a proof of principle, to assess both interspecies and interindividual differences in toxicodynamics. Electric eel enzyme and human blood of 20 different donors (12 men/8 women) were exposed to eight different compounds (chlorpyrifos, chlorpyrifos-oxon, phosmet, phosmet-oxon, diazinon, diazinon-oxon, pirimicarb, rivastigmine) and inhibition of AChE was measured using the Ellman method. The organophosphate parent compounds, chlorpyrifos, phosmet and diazinon, did not show inhibition of AChE. All other compounds showed concentration-dependent inhibition of AChE, with IC50s in human blood ranging from 0.2–29 µM and IC20s ranging from 0.1–18 µM, indicating that AChE is inhibited at concentrations relevant to the in vivo human situation. The oxon analogues were more potent inhibitors of electric eel AChE compared to human AChE. The opposite was true for carbamates, pointing towards interspecies differences for AChE inhibition. Human interindividual variability was low and ranged from 5–25%, depending on the concentration. This study provides a reliable in vitro method for assessing human variability in AChE toxicodynamics. The data suggest that the default uncertainty factor of ~ 3.16 may overestimate human variability for this toxicity endpoint, implying that specific toxicodynamic-related adjustment factors can support quantitative in vitro to in vivo extrapolations that link kinetic and dynamic data to improve chemical risk assessment.

show abstract

Human Erythrocyte Acetylcholinesterase in Health and Disease

Cited by 57 publications

References 71 publications

Exposure to cholinesterase inhibiting insecticides and blood glucose level in a population of Ugandan smallholder farmers

Exposure to cholinesterase inhibiting insecticides and blood glucose level in a population of Ugandan smallholder farmers

Natural Antioxidants Beneficial Effects on Anion Exchange through Band 3 Protein in Human Erythrocytes

Acetylcholinesterase inhibition in electric eel and human donor blood: an in vitro approach to investigate interspecies differences and human variability in toxicodynamics

Contact Info

Product

Resources

About