Tebuconazole induced oxidative stress and histopathological alterations in adult rat heart

Othmène, Yosra Ben; Hamdi, Hiba; Amara, Ines; Abid‐Essefi, Salwa

doi:10.1016/j.pestbp.2020.104671

Cited by 21 publications

(5 citation statements)

References 67 publications

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“…Orally treated rats with TEB at 0.9, 9, 27, and 45 mg/kg b.w. for 28 days, showed increased levels of malondialdehyde, a marker of ROSmediated lipid peroxidation injury, and advanced protein oxidation (Ben Othmène et al, 2020a). Various histological changes in the myocardium, including leucocytic infiltration, hemorrhage congestion of cardiac blood vessels, and cytoplasmic vacuolization were also reported.…”

Section: Discussionmentioning

confidence: 93%

“…Importantly, TEB accumulation in the cardiac tissue was found at an amount of 0.92 mg/kg at the end of the study. The work provided by Ben Othmène et al (2020aOthmène et al ( , 2020b, for example, indicates that the TEB concentration range in which, supposedly, no adverse effects are observed by The no-observed-adverse-effect-level (NOAEL), can cause significant remodeling in the cardiac tissue, thus suggesting that the NOAEL should be revised.…”

Section: Discussionmentioning

confidence: 99%

“…However, toxicological evaluation covering its potential cardiotoxicity is much less explored. Some recent studies described that TEB may induce heart injury (Ben Othmène et al, 2020a), with myocardial fibrosis. Oral administration of TEB during 28 days induced oxidative stress and histopathological alterations in rats' hearts (Ben Othmène et al, 2020b).…”

Section: Introductionmentioning

confidence: 99%

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The fungicide Tebuconazole induces electromechanical cardiotoxicity in murine hearts

Santos‐Miranda

Joviano‐Santos

Cruz-Nascimento

et al. 2021

Preprint

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Tebuconazole (TEB) is an important fungicide that belongs to the triazole family. It is largely applied in agriculture and its use has increased in the last decade. Since TEB is stable in water and soil, long-term exposure of humans to this pesticide is a real threat. Acute toxicological studies to uncover the toxicity of TEB are limited, and there is evidence of an association between long-term exposure to TEB and damage of several biological systems, including hepatotoxicity and cardiotoxicity. In this paper, the effects of acute exposure of cardiomyocytes and murine hearts to TEB were addressed to elucidate its impact on electromechanical properties of the cardiac tissue. In whole-cell patch-clamp records, TEB inhibited both the total outward potassium current (IC50=5.7±1.5 μmol.l−1) and the L-type calcium current (IC50=33.2±7.4 μmol.l−1). Acute exposure to TEB at 30 μmol.l−1 prolonged the action potential duration as well as an induced out-of-pace action potential, and increased the sodium/calcium exchanger current in its forward and reverse modes. Moreover, sarcomere shortening and calcium transient in isolated cardiomyocytes was enhanced when cells were exposed to TEB at 30 μmol.l−1. In ex vivo experiments, TEB 30 μmol.l−1 caused significant electrocardiogram remodeling with prolonged PR, QRS, and QT interval duration. Accordingly, TEB exposure was prone to the appearance of arrhythmias. Combined, our results demonstrate that acute TEB exposure affects the cardiomyocyte's electro-contractile properties and triggers the appearance of ECG abnormalities, including conduction defects and arrhythmias.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The fungicide Tebuconazole induces electromechanical cardiotoxicity in murine hearts

Santos‐Miranda

Joviano‐Santos

Cruz-Nascimento

et al. 2021

Preprint

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“…Therefore, triazole pesticides could affect liver function in various aspects. On the other hand, they have also been reported to have a toxic effect on the kidney, causing kidney dysfunction [ 27 ]. Kidneys are the main excretion organs and the primary target organs of pesticides.…”

Section: Resultsmentioning

confidence: 99%

Stereoselective Toxicokinetic and Distribution Study on the Hexaconazole Enantiomers in Mice

Luo

Pang

Sun

et al. 2023

Toxics

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Hexaconazole (Hex) has been widely used in agricultural products, and its residues may pose a potential risk to human health. However, the metabolic behavior of Hex enantiomers in mammal organisms is still unknown, which is important for evaluating the differences in their toxicity. In this study, the distribution of S-(+)- and R-(−)-Hex in mice was detected by an ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS), and the mechanism differences in the toxicokinetic behavior were analyzed by molecular docking. Good linearities, accuracies, and precisions were achieved for S-(+)- and R-(−)-Hex, with recoveries of 88.7~104.2% and RSDs less than 9.45% in nine tissues of mice. This established method was then used to detect the toxicokinetic of Hex enantiomers in mice after oral administration within 96 h. The results showed that the half-lives of S-(+)- and R-(−)-Hex were 3.07 and 3.71 h in plasma. Hex was mainly accumulated in the liver, followed by the kidneys, brain, lungs, spleen, and heart. The enantiomeric fraction (EF) values of Hex enantiomers in most of the samples were below 1, indicating that S-(+)-Hex decreased faster than its antipode. The molecular docking showed that the binding of S-(+)-Hex with P450arom was much more stable than R-(−)-Hex, which verified the fact that S-(+)-Hex was prefer to decrease in most of the tissues. The results of this study could be helpful for further evaluating the potential toxic risk of Hex enantiomers and for the development and usage of its pure monomer.

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“…Although studies have reported the adverse effects of oxidative stress induced by carbendazim and tebuconazole [1,19,22,24,[32][33][34][35][36], it remained unclear whether they would be harmful when exposed at the ADI dose. In this research, carbendazim at its ADI dose had no effects on the liver, and led to no obvious damage to the hepatic redox homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Low Dose of Carbendazim and Tebuconazole: Accumulation in Tissues and Effects on Hepatic Oxidative Stress in Mice

Chen

Hou

et al. 2023

Toxics

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As two commonly used fungicides, carbendazim and tebuconazole are widely found in the environment and in foods. Studies have reported that these fungicides can induce hepatic oxidative stress and other health risks. Nevertheless, the influences of exposure to carbendazim and tebuconazole at their acceptable daily intake (ADI) doses on hepatic oxidative stress, and the residual distributions in mice remain unclear. To fill these gaps, ICR (CD-1) mice were exposed to carbendazim and tebuconazole at their ADI doses by oral administration for 4 weeks in this study. The results showed that tebuconazole accumulated primarily in the epididymal fat of mice (16.84 μg/kg), whereas no significant residues of carbendazim in the tissues were observed. In addition, exposure to ADI doses of tebuconazole significantly reduced liver coefficients and induced hepatic oxidative stress in mice, including elevating the levels of glutathione and malonaldehyde. However, no significant impacts were observed on the hepatic redox homeostasis in mice after exposure to carbendazim at its ADI dose. The results could be helpful for understanding the exposure risks of carbendazim and tebuconazole in terms of low doses and long term.

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Tebuconazole induced oxidative stress and histopathological alterations in adult rat heart

Cited by 21 publications

References 67 publications

The fungicide Tebuconazole induces electromechanical cardiotoxicity in murine hearts

The fungicide Tebuconazole induces electromechanical cardiotoxicity in murine hearts

Stereoselective Toxicokinetic and Distribution Study on the Hexaconazole Enantiomers in Mice

Low Dose of Carbendazim and Tebuconazole: Accumulation in Tissues and Effects on Hepatic Oxidative Stress in Mice

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