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Role of Environmental Toxicants and Inflammation in Parkinson’s Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Biddut Deb Nath, Dipti Debnath, Rokeya Pervin, Md. Akil Hossain
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.
Metals
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Anirudh J. Chintalapati, Frank A. Barile
Patients reporting chronic Cd exposure are screened for renal and pulmonary functional changes to assess the extent of damage. Chelation therapy is not generally beneficial; however, the administration of dithiocarbamates is linked to a reduction in total Cd body burden. Chelation intervention may only be successful for Cd-induced dysfunction if the length, time, rate and concentrations associated with exposure are favorable enough to reverse significant or permanent damage. The age of the patient, the presence of concomitant pathological conditions and comorbidities, interactions with other pathological complications, and concomitant use of drug treatments may complicate the rate of successful recovery.
Agrochemicals: A Brief Overview
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Dithiocarbamates are a family of fungicides widely used since the 1940s to control fungal pathogens in a variety of crops. Compounds in this class include Maneb and Zineb (which include a metal moiety, manganese, and zinc, respectively) and Thiram (which does not have a metal moiety). These compounds have low acute toxicity, but chronic exposure is associated with adverse effects that may be due to the dithiocarbamate acid or the metal moiety. An important common metabolite of dithiocarbamates is ethylenethiourea, which is responsible for their effects on the thyroid (alterations of thyroid hormone levels, thyroid hypertrophy, and tumors) (110). Chronic exposure to Maneb has been associated with parkinsonism, possibly because of exposure to manganese, rather than the dithiocarbamate (111), and this fungicide has been recently withdrawn from the U.S. market (112). Interestingly, the structure of dithiocarbamate fungicides resembles that of disulfiram, an inhibitor of aldehyde dehydrogenase used in the treatment of alcoholism; for this reason, dithiocarbamates may interact with alcohol, leading to elevation in acetaldehyde levels (109). In addition, inhibition of aldehyde dehydrogenase, which also metabolizes DOPAL (3,4-dihydroxy phenyl acetaldehyde), a toxic metabolite of dopamine, is emerging as an important mechanism for a pesticidal etiology of Parkinson disease (113).
Pre-imaginal exposure to mancozeb induces morphological and behavioral deficits and oxidative damage in Drosophila melanogaster
Published in Drug and Chemical Toxicology, 2023
Cynthia Camila Ziech, Nathane Rosa Rodrigues, Giulianna Echeverria Macedo, Karen Kich Gomes, Illana Kemmerich Martins, Jeferson Luis Franco, Thaís Posser
MZ is described as a mildly toxic compound for vertebrates; however, toxicological studies indicated pro-oxidative effects causing DNA damage and cell death in human and rat cells (Calviello et al. 2006, Srivastava et al. 2012). Moreover, our group reported alterations in oxidative stress markers in Cyprinus carpio (Costa-Silva et al. 2018) and adult Drosophila melanogaster (Saraiva et al. 2018). Besides, exposure to similar dithiocarbamates caused neurotoxic effects and Parkinson-like symptoms in humans and Caenorhabditis elegans model (Zhou et al. 2004, Negga et al. 2011, Harrison Brody et al. 2013), and hormonal disruption in humans (Román 2007, Goldner et al. 2010). MZ contamination was also associated with human neural tube defects (Nordby et al. 2005), and prenatal MZ exposure retarded rat’s physical development (Castro et al. 1999). Recent studies have associated farmers’ exposure to MZ with sleep problems (Fuhriman et al. 2022). In this aspect, there is no information about the implication of embryonic exposure to MZ on oxidative stress parameters, metabolism indicators, and sleep quality.
Analytical and toxicological aspects of dithiocarbamates: an overview of the last 10 years
Published in Toxicology Mechanisms and Methods, 2022
Jéssica Cristina Romoli, Deborah Thais Palma Scarferla, Raul Gomes Aguera, Renata Sano Lini, Giseli Cristina Pante, Carlos Roberto Bueno Junior, Juliana Cristina Castro, Simone Aparecida Galerani Mossini, Camila Marchioni, Miguel Machinski Junior
In contrast, they are highly toxic to humans, animals and the environment. The application of fungicides by spraying on plantations directly exposes farmers and their families, since these compounds can leave the field and spread through the air, soil and water, putting the health of the population at risk (Kamel and Hoppin 2004; Regueiro et al. 2015). In addition, exposure to fungicides can also occur indirectly, through the ingestion of fruits and vegetables that contain residues of these pesticides (Schmidt et al. 2013). Groups of different types of fungicides can be classified, according to the Fungicide Resistance Action Committee (FRAC), based on the biochemical mode of action in the plant pathogen biosynthetic pathways (processes in the metabolism starting from nucleic acids synthesis to secondary metabolism) (FRAC 2020). Dithiocarbamates (DTCs) belong to the group of chemicals with multi-site activity. They can simultaneously interfere with the functioning of various organelles and biological processes of fungal cells (Balardin et al. 2017). They have been widely used since the 1940s to control fungal diseases in fruit and vegetables, both in storage and transportation (Zhu et al. 2017; Fanjul-Bolado et al. 2021).
Discovery of orally active chalcones as histone lysine specific demethylase 1 inhibitors for the treatment of leukaemia
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Yang Li, Ying Sun, Yang Zhou, Xinyang Li, Huan Zhang, Guojun Zhang
The LSD1 inhibitory activity of all synthesised compounds C1∼C4 and D1∼D7 was examined according to reported references [24,27]. Their results of inhibitory activities against LSD1 in vitro were summarised in Table 1. In this work, Dithiocarbamate 26 and chalcone 4 were used as reference compounds. The replacement of the chlorine atom by the dithiocarbamate fragment resulted in a powerful improvement of LSD1 inhibitory activity for chalcone-dithiocarbamate derivatives D1∼D7 compared with the corresponding chalcone analogues (C1∼C4). Especially, compound D6 showed the potently inhibitory effect with an IC50 value of 0.14 μM (> 100-fold more potent than C3). This result suggests that dithiocarbamate moiety may play a synergistic role in determining activity.