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Nitric Oxide as a Signaling Molecule in the Systemic Inflammatory Response to LPS
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
An unexpected finding was reported by Togashi et al. (110), who showed that the putative radical scavenger pyrrolidine dithiocarbamate (PDTC) activated NFκB in resting astroglial cells. The authors attributed this effect to the ability of the thiocarbamate to form iron chelates (115) that scavenged NO. This finding illustrates some of the complexities inherent in the use of PDTC as a probe for κB-dependent transcriptional activation. Besides radical scavenging, thiocarbamates can affect cellular redox status by a variety of mechanisms, including the promotion of metal uptake by cells, intracellular chelation of free metals, carbamoylation of proteins, and direct inhibitory effects on the glutathione redox cycle (100,115,116). Thus, in many respects the “antioxidant” PDTC should be considered a pro-oxidant. Moreover, the effects of PDTC are not specific to NF-κB, as the activation of AP-1 has also been shown to be PDTC-sensitive (117).
Environmental toxicants on Leydig cell function
Published in C. Yan Cheng, Spermatogenesis, 2018
Leping Ye, Xiaoheng Li, Xiaomin Chen, Qingquan Lian, Ren-Shan Ge
Molinate is a thiocarbamate that is a selective herbicide to control weeds. Exposure to molinate (40 mg/kg BW/day) to rats for 7 days inhibited testosterone levels.195 Ziram is a widely used thiocarbamate fungicide for crops. Ziram competitively inhibited rat 11βHSD1 with an IC50 of 87.07 μM. Ziram noncompetitively inhibited both rat and human 11β-HSD2 with IC50 values of 90.26 and 34.93 μM, possibly interacting the cysteine residues of 11β-HSD2.196 Thiram is a thiocarbamate fungicide and animal repellent. It inhibited human 11β-HSD2 with a similar mechanism to ziram.197
Pesticides and Chronic Diseases
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
Except for some moderate irritant effects on skin, respiratory tract, and eyes, the (mono) thiocarbamate herbicides do not appear to be highly toxic, but they do exacerbate chemical sensitivity. Extreme doses in laboratory animals do produce paralysis. There is a very remote possibility of “Antabuse” reactions from ethanol following extraordinary exposure to these (mono) thiocarbamates. They do not form ET on degradation.
Studies on oral subacute toxicity of cartap in male mice
Published in Drug and Chemical Toxicology, 2021
Laxman P. Sharma, Mayur P. Kadve, Madhu C. Lingaraju, Avinash G. Telang
Though cartap toxicity has been considered to be minimal, carbamates have been reported to have high mammalian toxicity, and the main target organs are brain, liver, skeletal muscles, and heart (Gupta 1994, Risher et al. 1987). In addition, kidney and reproductive functions have been reported to be adversely affected with carbamate exposure to rats (Kareem et al. 2007, Bindali and Kaliwal 2002). Cartap-induced cellular death in C2C12 cell line of mouse skeletal muscle has been shown to be mediated by generation of reactive oxygen species (ROS) (Liao et al. 2006). Antioxidant systems neutralize ROS and reduce their damaging abilities but when there is any imbalance in oxidant and internal antioxidant defense mechanism oxidative stress will result which causes lipid peroxidation, cross linking of DNA and protein (Romero et al. 1998). Carbamates are also known to cause significant changes in total serum lipids, glucose, protein levels, AST, ALT, acid phosphatase and alkaline phosphatase activities in mammals (Sadek et al. 1989, Fayez and Kilgore 1992, Chevalier et al. 1993). However, there are no known reports available on mid- or long-term toxic effects of cartap, a thiocarbamate in animal models. Therefore, the present study was carried out to investigate the effects of cartap on oxidative stress and histopathological alteration in vitals like liver, kidney, and brain of mice after 28 days oral exposure.
Mono- and di-thiocarbamate inhibition studies of the δ-carbonic anhydrase TweCAδ from the marine diatom Thalassiosira weissflogii
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Silvia Bua, Murat Bozdag, Sonia Del Prete, Fabrizio Carta, William A. Donald, Clemente Capasso, Claudiu T. Supuran
The first inhibition study of a δ-CA with mono- and di-thiocarbamates, classes of CAIs recently discovered, was reported. TweCAδ from the marine diatom T. weissflogii was not particularly sensitive to inhibition by these classes of compounds. Many of the mono- and di-thiocarbamates did not show inhibitory action up to 20 µM, whereas some aliphatic, heterocyclic, and aromatic inhibited this enzyme in the low micromolar range. Several MTCs/DTCs incorporating the piperazine ring effectively inhibited TweCAδ with KIs in the range of 129–791 nM. The most effective inhibitors identified were 3,4-dimethoxyphenyl-ethyl-mono-thiocarbamate (KI of 67.7 nM) and the R-enantiomer of the nipecotic acid DTC (KI of 93.6 nM). Such inhibitors can now be used as molecular probes to investigate the role of this enzyme in the carbon fixation processes in diatom marine organisms that are responsible for removing large amounts of CO2 from the atmosphere.
Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution
Published in Critical Reviews in Toxicology, 2018
S. Rotter, A. Beronius, A. R. Boobis, A. Hanberg, J. van Klaveren, M. Luijten, K. Machera, D. Nikolopoulou, H. van der Voet, J. Zilliacus, R. Solecki
US EPA has grouped a number of pesticides for the assessment of risks from combined exposure. Potential membership of a CMG is based on similarities in chemical structure and pesticidal mode of action. To date, CMGs have been created for: organophosphates, N-methyl carbamates, chloracetanilides, triazines, naturally occurring pyrethrins and synthetic pyrethroids. US EPA also examined thiocarbamates and dithiocarbamates as potential CMGs, but determined the available evidence did not support inclusion in a common mechanism group.