Role of Environmental Toxicants and Inflammation in Parkinson’s Disease
Abhai Kumar, Debasis Bagchi in Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Ziram (zinc dimethylbisdithiocarbamate), zineb (zinc ethylenebisdithiocarbamate), maneb (manganese ethylenebisdithiocarbamate), and other similar compounds are combined to form dithiocarbamates, which is widely used as fungicides. In animals, maneb induces specific neurodegeneration with dopaminergic influence. This interferes with mitochondrial activity, enhances oxidizing stress, and restricts proteasomal activity.169,170 Unlike MPP+, maneb prevents mitochondrial Complex III selectively. Ziram destroys dopaminergic neurons in culture by preventing the ubiquitin-proteasome system’s E1 ligase.171 Epidemiological research assessing concentrations of dithiocarbamate utilizing pesticide user details and spatial mapping observed an elevated incidence to PD correlated with zineb, ziram, and maneb.9,11 Together with toxicological data,172 these researches indicate possible synergy with paraquat.
Managing Pesticide Chronic Health Risks: U.S. Policies
Ana Maria Osorio, Lynn R. Goldman in Proceedings from the Medical Workshop on Pesticide-Related Illnesses from the International Conference on Pesticide Exposure and Health, 2017
At the time Congress required pesticide reregistration, there was particular focus on 10 carcinogenic pesticides: linuron, zineb, captafol, captan, maneb, permethrin, mancozeb, folpet, chlordirneform, and chlorothalonil. The National Research Council in 1985 had reported that these 10 pesticides accounted for 80 to 90 percent of the total estimated dietary cancer-causing risk from the 28 carcinogenic pesticides that were then commonly found on food.12 By 1995, the GAO found that the EPA had made significant progress toward regulating these pesticides,13 however, it took a long time for EPA to get the job done. Reassessments for mancozeb and maneb were completed in 2005, 20 years after the NRC report; the reassessment for permethrin was completed a year later.
Environmental toxicants on Leydig cell function
C. Yan Cheng in Spermatogenesis, 2018
Carbamates are used as insecticides and fungicides. Maneb is a widely used fungicide in agriculture. Exposure of maneb (1 and 4 mg/kg BW/day, i.p.) for 9–18 days to male rats reduced testosterone production and CYP11A1 activity in Leydig cells.192 Carbendazim is a metabolite of benomyl, one of the most widespread environmental contaminants. Exposure to carbendazim (25 mg/kg BW/day) to male rats for 48 days significantly reduced testosterone levels and 3β-HSD and 17β-HSD3 activities without affecting serum LH levels.193 Exposure to carbendazim to rats also caused an increase in ROS production and the downregulation of Star mRNA levels. The addition of a flavonoid can prevent this, suggesting an ROS-inducing mechanism.194
Manganese-induced neurodegenerative diseases and possible therapeutic approaches
Published in Expert Review of Neurotherapeutics, 2020
Airton C. Martins, Priscila Gubert, Gustavo R. Villas Boas, Marina Meirelles Paes, Abel Santamaría, Eunsook Lee, Alexey A. Tinkov, Aaron B. Bowman, Michael Aschner
Human exposure to Mn mainly occurs via intake of contaminated food and water, by occupational sources (inhalation of industrial applications, dust, mist, or fumes with Mn), and by environmental sources which include pesticides containing Mn [101]. Maneb (ethylenebis-dithiocarbamate) is a Mn-containing fungicide whose chronic exposure may produce symptoms and signs of central nervous system (CNS) Mn poisoning. Maneb exposure in rats caused a reduction in fertility and testosterone levels. In contrast, its co-administration with Basella alba L. (Basellaceae) extract minimized such changes in reproductive function [153]. B. alba showed efficacy in restoring the antioxidant system in the testicular tissue likely due to the presence of various antioxidant compounds, including phenolic compounds, carotenoids, ascorbic acid, saponins, coumarins and limonoids [154]. Finally, beyond the pharmacological advantages of plants usage, an extensive historical background of their consumption is available, thus reducing toxicological risks and adverse effects when compared to newly synthesized molecules.
The effect of Zataria multiflora hydroalcoholic extract on memory and lung changes induced by rats that inhaled paraquat
Published in Nutritional Neuroscience, 2021
Mahrokh Heydari, Amin Mokhtari-Zaer, Fatemeh Amin, Arghavan Memarzia, Saeideh Saadat, Mahmoud Hosseini, Mohammad Hossein Boskabady
Previous studies indicated that PQ affects nervous system and increases the incidence of neurodegenerative disorders such as Parkinson's and Alzheimer's [9,10]. The effect of PQ poisoning on learning and oxidative stress was reported in several studies. It was shown that PQ administration can induce oxidative damage in the hippocampus, and then influence the learning and memory abilities of adult mice [37]. The effect of orally administered PQ (0, 0.89, 2.67, and 8 mg/kg body weight for 28 days) on the hippocampus of mice showed irregular and condensed cytoplasm of hippocampus cells as well as reduced Nissl bodies and apoptotic or necrotic neuron. Paraquat toxicity also increased MDA, reactive oxygen species (ROS), and 8-OHdG in mitochondrial DNA (mtDNA) levels, but decreased SOD and concentration of adenosine-triphosphate (ATP) in the hippocampus. Impairment of spatial memory evaluated by MWM test was also seen due to PQ administration in this study [11,38]. In PQ and maneb-exposed mouse model also, impaired spatial learning and memory was demonstrated. In addition, reduced tyrosine hydroxylase expression and increased neurodegeneration, synaptic loss, α-synuclein expression, and Ser129-phosphorylation in the hippocampus were also observed [39]. The exposure to these two toxins also reduced the expression of cAMP and related genes and proteins in the hippocampus, which indicated reduction of the phosphorylation and inhibition of the activation of BDNF [40]. Administration of PQ (1.25 mg/kg, i.p.) caused spatial learning and memory impairment in mice and inhibited the proliferation of neural progenitor cells in the hippocampus. Caspase-3 and glial fibrillary acidic protein expression were also increased in PQ-administered mice [41].
Targeting macrophage polarization by Nrf2 agonists for treating various xenobiotics-induced toxic responses
Published in Toxicology Mechanisms and Methods, 2021
Yi-Ran Wang, Xiu-Ning Zhang, Fan-Ge Meng, Tao Zeng
During the last few decades, the concept of macrophage polarization and its roles in inflammatory diseases have been increasingly recognized. A great number of studies highlight that the uncontrolled or excessive M1 macrophages-driven inflammation plays pivotal roles in the pathogenesis of various xenobiotics-induced toxic responses. For example, Kupffer cells, the resident macrophages in liver, have been demonstrated to be the key contributor to many hepatotoxicants (such as ethanol and acetaminophen)-induced liver injuries (Wan et al. 2014; Ju and Mandrekar 2015). Many toxicants and environmental insults-induced neurotoxicity is thought to be mediated by the activation of microglia, the resident macrophages in brain (Kraft and Harry 2011). For instance, paraquat and maneb-induced neuroinflammation in mice was attributed to the M1 activated microglia (Che et al. 2018). Proinflammatory polarized macrophages have also been demonstrated to play crucial roles in toxicants-induced acute lung injuries (Laskin et al. 2019). Mice deficient in Tlr4 or the downstream signaling molecules including MyD88 or Nfkb were protected from lung toxicity induced by ozone, endotoxin, bleomycin, silica, and particulate matter (Laskin et al. 2011; Connor et al. 2012; Re et al. 2014; He et al. 2016). Furthermore, depletion of macrophages by clodronate-containing liposome or GdCl3 could attenuate a variety of toxicants-induced deleterious effects such as cigarette smoke-induced inflammatory response in the mouse colon and lung, ethanol-induced liver damage, the lethality of Shiga toxin-2, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced a cholangiopathy (Palermo et al. 1999; Ju and Mandrekar 2015; Best et al. 2016; Lim et al. 2018). Collectively, proinflammatory polarized macrophages play critical roles in the development of various kinds of xenobiotics-induced toxic responses, and regulating macrophage polarization would be promising approach for treating various toxicants-induced injuries.
Related Knowledge Centers
- Fungicide
- Coordination Complex
- Manganese
- Dithiocarbamate
- Ligand
- Animal Disease Model
- Parkinson's Disease
- Pesticide
- Metam Sodium
- Zineb