Dithiocarbamate fungicides increase intracellular Zn2+ levels by increasing influx of Zn2+ in rat thymic lymphocytes

Kanemoto-Kataoka, Yumiko; Oyama, Tomohiro M.; Ishibashi, Hiroyuki; Oyama, Yasuo

doi:10.1016/j.cbi.2015.05.014

Cited by 17 publications

(7 citation statements)

References 44 publications

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“…The potency of IT-354 as an elevator of intracellular Zn 2+ concentration is similar to that of Zineb (KanemotoKataoka et al, 2015). The concentrations of IT-354 that elevate intracellular Zn 2+ levels are 10-30 times higher than those of DCOIT and Ziram (Kanemoto-Kataoka et al, 2015). Therefore, the concentrations of IT-354 that alter Zn 2+ and Ca 2+ homeostasis in rat thymocytes under in vitro conditions are similar to those of phenylsulfamides and Zineb, but higher than those of DCOIT and Ziram.…”

Section: Discussionmentioning

confidence: 85%

Cytotoxic actions of N-(2,4,6-trichlorophenyl)maleimide (IT-354), an antifouling agent, in rat thymic lymphocytes

Fukunaga

Saito

Kurumi

et al. 2015

Fundam. Toxicol. Sci.

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-Of antifoulants that are substitutes for organotin compounds such as tributyltin and triphenyltin, N-(2,4,6-trichlorophenyl)maleimide (IT-354) is listed as a much less toxic agent, although the available information concerning IT-354 toxicity is the results of acute toxicity tests in freshwater fish. In this study, the effects of IT-354 on rat thymic lymphocytes were examined using flow-cytometric techniques with appropriate fluorescent probes in order to estimate the effects of IT-354 on mammalian cells. Treatment of cells with 1-10 μM IT-354 for 1 hr did not increase the population of dead cells (cell lethality). However, 10 μM IT-354 significantly increased the population of living, annexin V-positive cells. Annexin V-positive, living cells are expected to be undergoing apoptosis. IT-354 at 3-10 μM significantly elevated intracellular Ca 2+ and Zn 2+ levels mainly by increasing Ca 2+ influx and intracellular Zn 2+ release. Furthermore, IT-354 significantly depolarized membranes and decreased cellular non-protein thiol content. Assessments using selected antifouling agents showed that the cellular actions of IT-354 are most likely similar to those of other commonly used antifouling agents. Therefore, the toxic potency of IT-354 on wild mammals is speculated to be similar to those of the other tested antifoulants.

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Section: Discussionmentioning

confidence: 85%

Cytotoxic actions of N-(2,4,6-trichlorophenyl)maleimide (IT-354), an antifouling agent, in rat thymic lymphocytes

Fukunaga

Saito

Kurumi

et al. 2015

Fundam. Toxicol. Sci.

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“…The oxidation of thiols to disulfides resulted in Zn 2+ release from the thiols of proteins and nonproteins. 5 Ziram raised [Zn 2+ ] i , but not [Ca 2+ ] i , and increased the living cells that were positive to annexin V. 6 Therefore, we hypothesize that Ziram exhibits Zn 2+ -dependent cytotoxicity. The previous study lacks information on the effect of zinc on cell lethality caused by Ziram, the mechanism of action of sublethal levels of Ziram in the presence of environmentally relevant levels of zinc, and its implication in toxicological and environmental sciences.…”

Section: Introductionmentioning

confidence: 86%

Zinc is a determinant of the cytotoxicity of Ziram, a dithiocarbamate fungicide, in rat thymic lymphocytes: possible environmental risks

et al. 2017

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Ziram, one of the dithiocarbamate fungicides, is widely applied to agriculture because this agent protects various crops from fungal infections. Risks of dithiocarbamate biocide use are of concern. It was previously reported that Ziram increased the intracellular concentration of Zn. Therefore, we cytometrically studied the mechanism of Zn-dependent lethal actions of Ziram on rat lymphocytes at environmentally relevant Zn levels. Membrane and cellular parameters of rat lymphocytes were estimated by flow-cytometric techniques with appropriate fluorescent probes. The Ziram-induced increase in cell lethality was completely attenuated by Zn chelators. A significant increase of cell lethality was found on the simultaneous application of Ziram at a sublethal concentration and ZnCl. The combination of Ziram and ZnCl increased the cellular superoxide anion content and decreased the cellular GSH content, which possibly caused the increase in cell lethality. The zinc concentrations under the present experimental conditions were comparable to the environmentally relevant concentrations found in rivers. Therefore, the environmental level of zinc may be critical in estimating the toxicity of Ziram to wild animals.

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“…The phosphorus atom in the tetraphenylphosphoniun cation present tetrahedral distorted geometry, with P−C and C−C bond lengths in the range from 1.787(6) to 1.797(5) Å and 1.360(10) to 1.408(8) Å, respectively. The C−P−C angles in the four phenyl rings go from 107.4 (2) to 111.5(3)°. These values are comparable to those found in other structures with the same cation.…”

Section: Table 2 Selected Bond Lengths and Torsion Angles For Compoumentioning

confidence: 99%

“…The analysis of the results (Table 6) was not straightforward when considering the presence of these groups in the structures. The effect of both nitro (2) and trifluoromethyl (3) substituents on the IC 90 values are positive for the inhibition of H. vastatrix when considering the analogues with the longer carbon chains (c and d). Nevertheless, these substituents lower the inhibition of H. vastatrix germination when the allyldithiocarbimates bear short alkyl groups (a and b).…”

Section: Antifungal Activitymentioning

confidence: 99%

“…For example, Ziram, whose active principle is the zinc dimethyldithiocarbamate (ZDMC), is used either single or in mixtures with more specific systemic fungicides. 1 Even though the metaldithiocarbamates do not present high toxicity when compared to other fungicides, the literature 2 reports that Ziram and other zinc-dithiocarbamates increase the intracellular levels of Zn 2+ , which might induce apoptosis and other adverse events. In addition, it has been recently discovered that Ziram inhibits androgen production and steroidogenic enzyme activities in rat Leydig cells, in vitro.…”

Section: Introductionmentioning

confidence: 99%

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New Allyldithiocarbimates: Synthesis, Structure and Antifungal Activity against Phakopsora pachyrhizi and Hemileia vastatrix

Vidigal¹,

Rubinger²,

Silva³

et al. 2020

J. Braz. Chem. Soc.

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Twelve tetraphenylphosphonium allyldithiocarbimates were synthesized and fully characterized by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), infrared and nuclear magnetic resonance (NMR) spectroscopies. The spectroscopic data indicated that the allyldithiocarbimate anions present Z configuration, as confirmed by X-ray crystallography. These new compounds inhibited the germination of Phakopsora pachyrhizi and Hemileia vastatrix at very low doses, with IC 50 (concentration to achieve 50% of inhibition of spore germination) values ranging from 0.028 to 0.166 mmol L-1 , and IC 90 (concentration to achieve 90% of inhibition of spore germination) values varying from 0.156 to 0.528 mmol L-1. Allyldithiocarbimate salts are lead compounds for the development of new antifungals for coffee leaf rust and Asian soybean rust, devastating plant diseases with limited control options.

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Dithiocarbamate fungicides increase intracellular Zn2+ levels by increasing influx of Zn2+ in rat thymic lymphocytes

Cited by 17 publications

References 44 publications

Cytotoxic actions of N-(2,4,6-trichlorophenyl)maleimide (IT-354), an antifouling agent, in rat thymic lymphocytes

Cytotoxic actions of N-(2,4,6-trichlorophenyl)maleimide (IT-354), an antifouling agent, in rat thymic lymphocytes

Zinc is a determinant of the cytotoxicity of Ziram, a dithiocarbamate fungicide, in rat thymic lymphocytes: possible environmental risks

New Allyldithiocarbimates: Synthesis, Structure and Antifungal Activity against Phakopsora pachyrhizi and Hemileia vastatrix

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