The role of hepatic cytochrome P450s in the cytotoxicity of sertraline

Chen, Si; Wu, Qiangen; Li, Xilin; Li, Dongying; Fan, Michelle; Ren, Zhen; Bryant, Matthew; Mei, Nan; Guo, Lei

doi:10.1007/s00204-020-02753-y

Cited by 21 publications

(10 citation statements)

References 55 publications

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“…For both HepG2 and Caco2, an approximately 20% decrease in cell survival after a 24 h incubation period is observed for an initial SER concentration of 6.25 µM. This agrees with data obtained previously for HepG2 cells treated with SER [48]. It was found that for SER concentrations above 12.5 µM, which corresponds to 3.8 mg/L for both HepG2 after a 48-h incubation period and Caco2 after a 24-h incubation period, an acute cytotoxic effect is observed, and cell survival is below 20% compared to the control solution.…”

Section: Cytotoxicity Monitoringsupporting

confidence: 91%

“…At a concentration of 7.5 µM sertraline, cell viability was reduced to approximately 83% compared to the DMSO control. Moreover, HepG2 viability detected by MTS decreased to about 23% when cells were treated with 15 µM sertraline, indicating that there was significant inhibition of growth and cell damage [48]. In the case of MCF-7 breast cancer cells, a much stronger effect was observed for sertraline, where the IC50 was approx.…”

Section: Cytotoxicity Monitoringmentioning

confidence: 96%

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Degradation of Selected Antidepressants Sertraline and Citalopram in Ultrapure Water and Surface Water Using Gamma Radiation

et al. 2021

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Gamma radiation was applied to degradation selected antidepressants in ultrapure water and surface water. Additionally, the influence of typical radical scavengers like carbonate, nitrate and humic acid was determined. The cytotoxicity towards liver cells HepG2 and colon cells Caco2 were measured during the radiation process. It was found that radiation technology, specifically ionizing radiation, can achieve satisfactory degradation efficiency with both SER and CIT. It was shown that the process of decomposition of the tested antidepressants with the highest efficiency occurs in the reaction with the hydroxyl radical.

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Section: Cytotoxicity Monitoringsupporting

confidence: 91%

Section: Cytotoxicity Monitoringmentioning

confidence: 96%

Degradation of Selected Antidepressants Sertraline and Citalopram in Ultrapure Water and Surface Water Using Gamma Radiation

et al. 2021

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“…Numerous genomic and pharmacogenetic factors have been proved to influence the metabolism of psychotropic drugs, which might subsequently affect the efficacy and side effects. Some studies confirmed that CYP2D6, 2C19, 2B6, and 2C9-mediated metabolism is responsible for the metabolism of sertraline and the metabolism mediated by these CYPs rescued the cytotoxicity of sertraline (Chen et al, 2020). It has been reported that the genetic polymorphisms in CYP2C19 may influence metabolism of the escitalopram and treatment response (Tsai et al, 2010).…”

Section: Discussionmentioning

confidence: 95%

Efficacy of antidepressant drugs in the treatment of depression in Alzheimer disease patients: A systematic review and network meta-analysis

He¹,

Li²,

Huang³

et al. 2021

J Psychopharmacol

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Background: Depression is considered as one of the most common neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) patients. Prescription of antidepressants is a current clinical practice well-established as the first-line treatment for such patients. Our study was aimed at systematically examining the evidence on the efficacy of antidepressants in the treatment of depression in AD patients. Methods: We conducted a network meta-analysis of randomized controlled trials retrieved by systematic search of the Cochrane Central Register of Controlled Trials, PubMed, Embase, and CNKI databases. Primary outcomes included mean depression score and safety. Secondary outcomes were cognition. The surface under the cumulative ranking curve was performed to estimate a ranking probability for different treatments. Results: A total of 25 studies including 14 medications met the inclusion criteria. Compared with placebo, only mirtazapine (standard mean deviation [SMD], −1.94; 95% confidence interval [CI], −3.53 to −0.36; p < 0.05) and sertraline (SMD, −1.16; 95% CI, −2.17 to −0.15; p < 0.05) showed a slightly better effect in treating symptoms of depression. Clomipramine increased risk of adverse events than placebo (odds ratio, 3.01; 95% CI, 1.45 to 4.57; p < 0.05). In terms of cognitive function, there was no statistically significant difference between antidepressants and placebo. Conclusion: Overall, in the short-term treatment, these data suggest that commonly used antidepressants sertraline and mirtazapine should be considered as an alternative treatment for depression in AD patients. However, more high-quality trials with large samples and longer following-up are proposed.

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“…2,3 Significant effects of CYP2C19 variants on sertraline metabolism have already been observed by several studies, whereas there are no studies of CYP2B6 and sertraline in a large patient population. [2][3][4][5][6] By contrast, CYP2D6 and CYP2C9 variants are not predictors of sertraline metabolism, as shown by Braten et al 5 Regarding CYP3A4, a study with grapefruit juice, 7 which is a potent inhibitor, reported a 1.5-fold increase in sertraline exposure during juice consumption, suggesting a relevant impact of CYP3A4 on sertraline metabolism alongside CYP2C19 and CYP2B6. 7 CYP2C19 and CYP2B6 are highly polymorphic which influences the metabolism of clinically relevant drugs.…”

Section: Introductionmentioning

confidence: 97%

Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population

Bråten

Ingelman‐Sundberg

Jukić

et al. 2022

Clinical Translational Sci

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Sertraline is a commonly used SSRI antidepressant drug, metabolized by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variants in order to identify the possible missing heritability for such variation in sertraline response in a large patient population (n = 840). Compared to the reference group (CYP2C19*1/*1, n = 160), sertraline exposure was increased by 128% in CYP2C19 PMs (n = 29, p < 0.001) and decreased by about 20% in CYP2C19 ultrarapid metabolizers (UMs) (homozygous carriers of CYP2C19*17 and/or CYP2C:TG haplotype) with the diplotypes CYP2C19*17/*17, CYP2C:TG/TG, or CYP2C19*17/CYP2C:TG (n = 135, p < 0.003, p = 0.022, p < 0.003, respectively). Interestingly, in patients carrying the increased function CYP2B6*4 allele, and also carrying the CYP2C19*17 and CYP2C:TG alleles (n = 10), sertraline exposure was 35.4% lower compared to the reference group, whereas in subjects being poor metabolizers (PM) in both the CYP2C19 and CYP2B6 gene, the sertraline concentrations were raised by 189%.In summary, the CYP2C19 variants including the CYP2C:TG haplotype had a significant impact on sertraline metabolism, as well as the CYP2B6*4, *6, and *9 alleles. Knowing the CYP2B6 and CYP2C19 genotype, including the CYP2C:TG haplotype status, can prospectively be useful to clinicians in making more appropriate sertraline dosing decisions. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?Sertraline is a commonly used antidepressant subjected to metabolism by multiple enzymes with CYP2C19 playing a key role along with CYP2B6 and CYP3A4. Previous pharmacogenetic studies have reported significant effects of CYP2C19 and CYP2B6 genotypes on sertraline concentration, but with inconsistent findings probably reflecting that the concurrent effects of the genotypes have not

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The role of hepatic cytochrome P450s in the cytotoxicity of sertraline

Cited by 21 publications

References 55 publications

Degradation of Selected Antidepressants Sertraline and Citalopram in Ultrapure Water and Surface Water Using Gamma Radiation

Degradation of Selected Antidepressants Sertraline and Citalopram in Ultrapure Water and Surface Water Using Gamma Radiation

Efficacy of antidepressant drugs in the treatment of depression in Alzheimer disease patients: A systematic review and network meta-analysis

Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population

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