ABSTRACT
Blood butyrylcholinesterase (BChE) activity has been found to decrease during pregnancy and reportedly decrease even more in preeclampsia (PE). The purpose of the present meta-analysis was to answer a specific question of whether BChE activity (in the plasma, serum, or whole blood) is reduced in pregnant women suffering from PE compared to those with normal pregnancy. The meta-analysis included 15 studies with 20 records of BChE activity in 608 women compared to 569 healthy pregnant (control) ones. The studies were subjected to quality assessment using the Newcastle-Ottawa Scale (NOS). Using the Meta-Essentials software program 1.5, the one-group random effects model and forest plot revealed that the percentage of BChE activity in pregnant women with PE was 84.84% of the control value, with a standard error of 4.09 and 95% C.I. of 76.28, 93.41, indicating a significant 15.16% reduction in BChE activity in comparison to healthy pregnancy. No significant heterogeneity was seen in the analyzed data and the funnel plot did show publication bias. Subgroup (mild, severe, and unclassified PE) forest plot analysis revealed that the % BChE activities in PE compared to respective healthy pregnancies were 96.28%, 97.08%, and 76.62%, respectively with no heterogeneity. The median NOS score of the 15 studies included in the meta-analysis was 7, ranging from 5 to 8 (medium to high quality), and the forest plot showed an effect size of 0.735. This meta-analysis shows that BChE activity is reduced in PE compared with normal pregnancy and its value as a biomarker warrants further clinical studies.
ABSTRACT
Background and Aim: Diphenhydramine is an H1-antihistamine that counteracts the toxic effects of organophosphate and carbamate insecticides that inhibit cholinesterase (ChE) activity. This meta-analysis aimed to investigate the effects of diphenhydramine on ChE inhibition induced by these insecticides in the plasma, erythrocytes, or whole brain of experimental animals. Materials and Methods: A data search was performed on erythrocyte, plasma, and brain ChE inhibition caused by organophosphate and carbamate insecticides in experimental animals (mice, rats, and chicks) treated with the antihistamine diphenhydramine in accordance with preferred reporting items for systematic reviews and meta-analysis, which was done by the two-group random-effects model meta-analysis. The meta-analysis included 18 records extracted from six studies that, appeared from 1996 to 2022. Results: Using the random-effects model, a two-group meta-analysis revealed that the combined effect size (ChE inhibition) was significantly more favorable in the control group than in the diphenhydramine intervention, as shown by a forest plot. The combined effect size (standardized mean difference) was 0.67, with a standard error of 0.3, a lower limit of 0.04, and an upper limit of 1.29 (p = 0.025). The heterogeneity was moderate, as I2 of the combined effect size was 74%, with a significant Cochrane Q-test result (Q = 65, p < 0.0001). Subgroup analysis indicated that, with brain ChE inhibition, the heterogeneity (I2) became 5%, which was lower than ChE inhibition in plasma (84%) and erythrocytes (78%). No publication bias was identified using the funnel plot and Egger's test. Conclusion: This meta-analysis suggests that, in addition to its documented antidotal action against ChE-inhibiting insecticides, diphenhydramine can also reduce the extent of ChE inhibition, especially in the brain, which is the main site of toxicity of these insecticides. There is a need for additional studies to assess such enzyme inhibition in different parts of the brain.
ABSTRACT
Measurements of blood cholinesterase (ChE) activities, including those of erythrocytes (EChE), plasma or serum (PChE), and whole blood (WBChE), are used to assess exposure to ChE-inhibiting pesticides. The purpose of this review was to report normal reference ChE activities in the blood of healthy adult humans, as determined by a modified electrometric method. We performed a systematic review following PRISMA guidelines. Single-group meta-analysis of means of PChE, EChE, and WBChE activities of adult healthy subjects was conducted using the random effects model. The programs used were Open-Meta Analyst and Meta-Essentials Version 1.5. Studies selected for analysis comprised 21, 19, and 4 reports of normal reference/baseline PChE, EChE, and WBChE activities in 690, 635, and 121 healthy adult males and/or females, respectively. The meta-analysis showed normal reference values of the means (effect sizes) with 95% CI of PChE, EChE, and WBChE activities of healthy adult subjects, which were 1.078 (1.015, 1.142), 1.075 (1.024, 1.125) and 1.331 (1.226, 1.436), respectively. By the subgroup analysis, heterogeneity (I2>89%) was considerably reduced in females to 4.4% and 30.1% for PChE and EChE, respectively. Funnel plots indicated no publication bias. However, Egger's regression confirmed the symmetry of the data points for PChE and WBChE activities with a significant effect on EChE. This meta-analysis showed normal reference values of PChE, EChE, and WBChE activities, measured by a modified electrometric method, in healthy adult humans.