Interaction of cigarette smoke condensate and some of its components with chlorpromazine toxicity on <i>Saccharomyces cerevisiae</i>

Sayyed, Katia; Aljebeai, Abdel-Karim; Al-Nachar, Mariam; Chamieh, Hala; Taha, Samir; Abdel-Razzak, Ziad

doi:10.1080/01480545.2019.1659809

Cited by 5 publications

(9 citation statements)

References 88 publications

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“…CPZ IC 50 was 28.08±1.03 µM and 43.83±1.02 µM after 6 and 24 hours of treatment, respectively. This result is not graphically illustrated, but in agreement with our previous work (Sayyed et al, 2019). CPZ toxic effect was antagonized by the antioxidant NAC, thereby demonstrating oxidative stress as a main toxicity mechanism.…”

Section: Resultssupporting

confidence: 89%

Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae

Muhieddine

Moughnié

Abdel-Razzak

2019

Interdisciplinary Toxicology

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Chlorpromazine (CPZ) is still a commonly prescribed antipsychotic which causes poorly understood idiosyncratic toxicity such as cholestasis, phospholipidosis and steatosis. CPZ has diverse cellular targets and exerts various toxicity mechanisms whose exploration is necessary to understand CPZ side effects. We report here that CPZ causes a decrease of total lipid content in Saccharomyces cerevisiae at the same dose range as that used on mammalian cells. The observed lipid decrease was obvious after 4 and 9 hours of treatment, and disappeared after 24 hours due to cells adaptation to the chemical stress. The inhibitory effect of CPZ was antagonized by the antioxidant N-acetyl L-cysteine and is likely caused by the parent compound. The obtained results demonstrate that yeast model is valid to investigate the involved CPZ toxicity mechanisms, particularly in terms of lipids alteration. This would contribute to understand CPZ side effects in simple model and reduce experimentation on animals.

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Section: Resultssupporting

confidence: 89%

Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae

Muhieddine

Moughnié

Abdel-Razzak

2019

Interdisciplinary Toxicology

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“…The choice of these different serial dilutions and combined concentrations aimed to generate enough data points to draw the sigmoid inhibition curves by non-linear regression and to calculate the combination index (CI) values. These combined concentrations were based on the previously reported IC50 of each toxicant alone, that is, ≈20 μ m for AMD, ≈70 μ m for HgCl 2 (Hosiner et al, 2014), and ≈50 μ m for CdCl 2 (Sayyed et al, 2019). For AMD and HgCl 2 combination, the highest combined concentrations were approximately 1.75×IC50 of each, and the lowest combined ones were approximately 0.55×IC50 of each.…”

Section: Methodsmentioning

confidence: 99%

Dose-dependent interaction of two heavy metals with amiodarone toxicity in Saccharomyces cerevisiae

et al. 2022

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Amiodarone (AMD) is an antiarrhythmic drug that induces idiosyncratic toxicity. Environmental pollutants, including heavy metals, could interact with its toxicity by affecting pharmacokinetics and pharmacodynamics. Other levels of interaction could exist in yeast, such as oxidative stress and the general stress response. In this study, we investigated the interaction of mercury chloride (HgCl2) and cadmium chloride (CdCl2) with AMD toxicity on Saccharomyces cerevisiae. Interaction type - synergistic, additive, or antagonistic - was determined by median drug effect analysis using “CompuSyn”. HgCl2 potentiated AMD toxicity at high doses (≥ 71.4 μm, which yielded more than 60% inhibition). CdCl2 acted similarly at high doses (≥ 57.9 μm). An antagonistic effect appeared at lower doses with both heavy metals (≤ 49.4 μm for HgCl2 and AMD; ≤ 18.9 μm for CdCl2 and AMD). The threshold concentrations (HgCl2 or CdCl2 combined with AMD) that switched the interaction from antagonistic to additive, and then to synergistic, were decreased in the yeast strain mutant in catalase ( CTT1), suggesting an important role for this enzyme. Moreover, mutation of the nutrient sensing receptor gene GPR1 caused the synergistic interaction of CdCl2, but not HgCl2, with AMD to occur at the lowest tested concentrations (1.2 μm). The reverse was obtained with the mutant strain in calcium–manganese transporter gene PMR1, where the synergistic interaction of HgCl2 with AMD occurred at concentrations (20.7 μm) lower than that of the wild type (71.4 μm). These results demonstrated a dose-dependent interaction between the two heavy metals with AMD toxicity, and the involvement of oxidative stress, calcium homeostasis, and nutrient sensing in the observed interaction.

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“…AMD toxicity was assessed at 6 and 24 h of treatment (1 to 240 μM) in the presence/absence of non-toxic CSC dose (160 μg/ml) (Sayyed et al, 2019). AMD decreased yeast growth in a dose-dependent manner at both time points, but IC 50 was lower at 6 h (19.59 μM) relative to 24 h (53.71 μM, Figure 1A,B), indicating yeast adaptation to the AMD-induced chemical stress.…”

Section: Csc Interacts With the Dose-dependent Toxicity Of Amdmentioning

confidence: 99%

“…AMD idiosyncratic toxicity may depend on genetic and environmental factors such as exposure to cigarette smoke. Several models, including Saccharomyces cerevisiae (S. cerevisiae), are valid to investigate drug toxicity and to identify potential interactions with pollutants such as cigarette smoke (Al-Attrache et al, 2018;Pena et al, 2009;Sayyed et al, 2018Sayyed et al, , 2019. AMD causes oxidative stress and induces relevant genes (e.g., catalase CTT1) in S. cerevisiae (Zhang & Rao, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Cigarette smoke interacts with amiodarone toxicity in Saccharomyces cerevisiae

Al-Attrache

Halloum

Hammoud

et al. 2022

J of Applied Toxicology

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Amiodarone (AMD) is an antiarrhythmic drug prescribed to treat ventricular tachycardia and fibrillation. However, it causes an unpredictable toxicity (idiosyncratic), which may depend on co‐exposure to pollutants. AMD toxicity involves calcium homeostasis alteration and oxidative stress, which are also affected by cigarette smoke (CS). We investigated the interaction of CS‐condensate (CSC), phenanthrene, and benzo(a)pyrene with AMD toxicity on Saccharomyces cerevisiae. AMD toxicity was reduced by CSC or phenanthrene. Benzo(a)pyrene mildly decreased AMD toxicity on the wild‐type strain, but not on the catalase‐CTT1 mutant. This latter and other mutants in glucose receptor‐GPR1 or calcium transporter‐PMR1 showed lower antagonistic effect to AMD by CSC or phenanthrene relative to the wild type, suggesting roles of oxidative stress, calcium homeostasis, and hexose‐sensing in this interaction.

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Interaction of cigarette smoke condensate and some of its components with chlorpromazine toxicity on Saccharomyces cerevisiae

Cited by 5 publications

References 88 publications

Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae

Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae

Dose-dependent interaction of two heavy metals with amiodarone toxicity in Saccharomyces cerevisiae

Cigarette smoke interacts with amiodarone toxicity in Saccharomyces cerevisiae

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