Mohammad Fouad K, Garmavy Hishyar M S, Mohammed Ammar A, Rashid Hussein M
Department of Physiology, Biochemistry, and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq.
Department of Pharmacology, College of Pharmacy, University of Duhok, Duhok, KRG, Iraq.
Vet World. 2023 Jan;16(1):118-125. doi: 10.14202/vetworld.2023.118-125. Epub 2023 Jan 16.
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.
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.
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 I 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 (I) 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.
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.
苯海拉明是一种H1抗组胺药，可对抗抑制胆碱酯酶（ChE）活性的有机磷酸酯和氨基甲酸酯类杀虫剂的毒性作用。本荟萃分析旨在研究苯海拉明对实验动物血浆、红细胞或全脑中这些杀虫剂诱导的ChE抑制的影响。
根据系统评价和荟萃分析的首选报告项目，对用抗组胺药苯海拉明治疗的实验动物（小鼠、大鼠和小鸡）中有机磷酸酯和氨基甲酸酯类杀虫剂引起的红细胞、血浆和脑ChE抑制进行数据检索，采用两组随机效应模型荟萃分析。该荟萃分析纳入了从1996年至2022年发表的6项研究中提取的18条记录。
采用随机效应模型进行的两组荟萃分析显示，如森林图所示，对照组的合并效应量（ChE抑制）显著优于苯海拉明干预组。合并效应量（标准化均值差）为0.67，标准误为0.3，下限为0.04，上限为1.29（p = 0.025）。异质性为中度，合并效应量的I2为74%，Cochrane Q检验结果显著（Q = 65，p < 0.0001）。亚组分析表明，对于脑ChE抑制，异质性（I2）降至5%，低于血浆（84%）和红细胞（78%）中的ChE抑制。使用漏斗图和Egger检验未发现发表偏倚。
本荟萃分析表明，除了其已记录的对ChE抑制性杀虫剂的解毒作用外，苯海拉明还可降低ChE抑制的程度，尤其是在脑中，而脑是这些杀虫剂的主要毒性部位。需要进一步研究以评估脑不同部位的这种酶抑制情况。
