Correlation between acute brain injury and brain metabonomics in dichlorvos-poisoned broilers
Graphical Abstract
Introduction
Dichlorvos (dimethyl dichlorovinyl phosphate, DDVP) is an organophosphorus pesticide that is mainly used in the control of plant diseases and insect pests. Because of its low cost and high efficiency, it has been widely used in agricultural production and water and landscape pest control (Wang et al., 2014). DDVP abuse has led to environmental pollution, and some nontarget organisms have become victims. Dwivedi et al. stated that there are 3 million reported cases of pesticide poisoning worldwide every year, and approximately 220,000 deaths due to pesticide poisoning, with DDVP being one of the most commonly used pesticides (Dwivedi et al., 2014). DDVP can enter the natural environment in a variety of ways, including the atmosphere, water, soil or biological media. DDVP has high stability, and its half-life ranges from more than 2 days to several weeks (Bui-Nguyen et al., 2015). This shows that DDVP can remain in soil, food and water, which affects human health, animal husbandry development and the ecological balance.
In recent years, toxicological studies on DDVP have mainly focused on chronic toxicity, developmental toxicity, and delayed neurotoxicity, and there are many studies on these aspects. With regard to the chronic toxicity of DDVP, some studies have reported that long-term exposure to DDVP can cause liver dysfunction and damage the endometrium in rats (Binukumar et al., 2010b, Oral et al., 2006), and delayed neurotoxicity can even occur after DDVP poisoning for a period of time (Choudhary and Gill, 2001, Sarin and Gill, 2000). In addition, Sişman and Altenhofen et al. reported that exposure to DDVP during early development can lead to abnormal development and behaviors and even death of zebrafish, proving the developmental toxicity of DDVP (Altenhofen et al., 2019, Sişman, 2010). However, the mechanism of acute neurotoxicity of DDVP has not been well studied. Acute DDVP exposure is mainly characterized by excessive stimulation of cholinergic receptors in the brain, resulting in cholinergic neuronal excitotoxicity and dysfunction, which can lead to secondary neuronal injury and chronic neuropsychiatric consequences (Chen, 2012). At the same time, delayed neuropathy may occur after acute exposure to DDVP for a few days to weeks (Masoud and Sandhir, 2012). However, there are no drugs for DDVP acute exposure to treat or prevent its acute neurotoxicity to reduce the incidence of secondary or delayed brain injury. Considering that chickens are susceptible to DDVP, the clinical symptoms and subsequent secondary or delayed brain injury symptoms after acute poisoning are similar to those of humans (Abou-Donia, 1981). Therefore, we urgently hope to use a new method to explore the effects of acute exposure to different doses of DDVP on brain injury in broilers.
Metabolomics is a powerful technique that provides a fair and comprehensive qualitative and quantitative overview of metabolites present in organisms and helps to understand how animals and plants respond to and alleviate various adversarial factors at the molecular level (Zhang et al., 2018). Metabonomics has been proven to be helpful in the study of toxicological mechanisms and is also applicable to disease diagnosis and treatment evaluation (Liu et al., 2015). Hoffman et al. used metabolomics to investigate the short-term and long-term variability of organophosphate flame retardant metabolites in the urine of pregnant women (Hoffman et al., 2014). Jiang et al. explained the mechanism of the effect of progesterone on the reproduction of zebrafish by metabolomics (Jiang et al., 2019).
Therefore, by using metabonomics combined with pathological observation, we studied acute brain damage caused by different doses of DDVP and screened differential metabolites in broilers to explore the pathogenesis of brain injury caused by acute DDVP poisoning and to provide new research ideas for the screening of diagnostic markers of brain injury caused by acute DDVP poisoning and the development of preventive and therapeutic drugs in the future.
Section snippets
Chemicals
DDVP (2,2-dichlorovinyl dimethyl phosphate) was purchased from Shandong Dacheng Agrochemical Co., Ltd. (Zibo, Shandong, China) and was 77.5% pure. All other chemicals used were of the highest grade.
Animals and their care
Fifty healthy 40-day-old broilers (average weight 1–2 kg) were purchased from the Laboratory Animal Center of Nanchang University. The broilers were kept in well-ventilated rooms with suitable temperature (20–25 °C) and humidity (55–60%) and housed in iron cages. The broilers were fed a standard
Clinical manifestations, blood glucose levels and changes in biomarkers of oxidative stress in broilers with acute DDVP poisoning
As shown in Fig. 1A, different doses of DDVP had obvious acute toxic effects on broilers. With an increase in DDVP dosage, the toxic symptoms of broilers were more obvious. In the early stage of poisoning, broilers showed signs of lethargy, salivation, dyspnea and diarrhea (even bleeding). Over time, they showed symptoms of general tremor, convulsions and even death. There was obvious brain edema in DDVP-poisoned broilers compared with the control group, and the distance of the cerebellar
Discussion
The purpose of this study was to investigate the effect of acute DDVP poisoning on brain injury in broilers. The results showed that acute poisoning symptoms could be found in broilers at the two concentrations, but there were differences between the two concentrations. The broilers in the high-dose group had spasms and even died, while the broilers in the low-dose group had intestinal injury symptoms such as diarrhea and bloody dysentery. Both groups had different degrees of hyperglycemia,
Conclusion
This work provides new insight into the metabolic response of brain tissue of broilers to short-term exposure to different concentrations of DDVP. The results showed that 2.48 mg/kg and 11.3 mg/kg DDVP could cause obvious poisoning symptoms, hyperglycemia and oxidative stress in broilers. In addition, these two doses can lead to changes in brain metabolites in broilers, and there are correlations between brain metabolites and hyperglycemia, oxidative stress and pathological damage.
CRediT authorship contribution statement
Lujia Huang: Data curation, Writing – original draft preparation. Xiaoquan Guo: Conceptualization, Methodology, Software. Pei Liu: Visualization, Investigation. Yulan Zhao: Supervision, Writing – review & editing. Cong Wu: Software, Validation. Changming Zhou: Software, Validation. Cheng Huang: Conceptualization. Guyue Li: Supervision. Yu Zhuang: Writing – review & editing. Sufang Cheng: Methodology. Huabin Cao: Methodology, Software. Caiying Zhang: Investigation. Zheng Xu: Visualization,
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This project was supported by the National Natural Science Foundation of China (No. 31960723, Beijing, P. R. China), the Natural Science Foundation of Jiangxi Province (No. 20171ACB21026) and the Technology R&D Program of Jiangxi Province (No. GJJ170243, Nanchang, P. R. China).
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These authors contributed equally to this study and share first authorship.