Home Tributyltin induces apoptosis in mammalian cells in vivo: a scoping review
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Tributyltin induces apoptosis in mammalian cells in vivo: a scoping review

  • Lucas Vilas Bôas Correia , Talita Trindade de Moraes , Aparecida Marta Regina dos Santos Pereira , Gabriel Carvalhal de Aguiar , Milena de Barros Viana , Daniel Araki Ribeiro EMAIL logo and Regina Cláudia Barbosa da Silva
Published/Copyright: August 6, 2024
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Reviews on Environmental Health
From the journal Reviews on Environmental Health Volume 40 Issue 1

Abstract

The present review aimed to evaluate the apoptotic effect of tributyltin (TBT) exposure on mammalian tissues and cells in vivo. A search was conducted in specialized literature databases including Embase, Medline, Pubmed, Scholar Google, and Scopus for all manuscripts using the following keywords: “tributyltin”, “apoptosis”, “mammals”, “mammalian cells’, “eukaryotic cells”, ‘rodents’, “rats”, “mice” and “in vivo” for all data published until September 2023. A total of 16 studies were included. The studies have demonstrated that TBT exposure induces apoptosis in cells from various mammalian organs or tissues in vivo. TBT is capable to increase apoptotic cells, to activate proapoptotic proteins such as calpain, caspases, bax and beclin-1 and to inhibit antiapoptotic protein bcl-2. Additionally, TBT alters the ratio of bcl-2/bax which favor apoptosis. Therefore, the activation of enzymes such as calpain induces apoptosis mediated by ERS and caspases through the intrinsic apoptosis pathway. This review has demonstrated that TBT exposure induces apoptosis in mammalian tissues and cells in vivo.

Keywords: TBT; apoptosis; mammalian cells; in vivo ; ERS; intrinsic pathway

Introduction

Tributyltin (TBT) is a tin-derived compound that has been widely used as a biocide in anti-fouling paints [1]. These paints are directed applied to submerged structures in the water column in order to prevent marine biofouling [2], 3]. However, this biocide in the paint leaches slightly into the seawater, causing harm to marine organisms attached to the hulls, as well as other non-target aquatic organisms [4].

The main way of TBT exposure is through consumption of contaminated fish and seafood [5]. In fact, TBT levels have been detected in human blood [6], indicating that exposure to this pollutant may pose substantial risk to exposed human populations. Currently, the use of TBT as a biocide in anti-fouling paints has been globally banned by the Convention on the Control of Harmful Anti-fouling Systems on Ships [7], due to its harmful effects on non-target marine organisms [8], [9], [10].

One of main issues related to TBT is its ability to induce apoptosis in mammalian cells. Apoptosis is the process of programmed cells death that plays a crucial role in normal cell turnover, proper development, embryonic development, chemical-induced cell death, functioning of immune system and hormone-dependent atrophy [11]. Living cells show biochemical and morphological changes that lead to cell death such as cell shrinkage, membrane bebbling, DNA condensation and fragmentation, which is accompanied by the formation of “apoptotic bodies” [12]. However, when it occurs in an unregulated manner, apoptosis can contribute to the development of diseases, including cancers, neurodegenerative disorders, immune dysfunctions and ischemic damage [13].

A growing number of in vitro studies has revealed a range of cellular and molecular alterations associated with apoptotic activation in different tissues and cells. For instance, TBT exposure has been associated with apoptotic effects primarily on the immune system [14], [15], [16]. Other studies have demonstrated apoptotic effects on neurons in vitro [17], as well as apoptotic effects on Leyding cells ex vivo [18]. However, studies have demonstrated the harmful effects on non-target animals, including its potential apoptotic effects on mammalian cells in vivo. Therefore, this scoping review aims to investigate the effects of TBT exposure on mammalian cells in vivo, by providing a comprehensive overview of the mechanisms involved based on the available scientific literature.

Materials and methods

Search strategy

An electronic search was conducted in databases such as: EMBASE, MEDLINE, PUBMED, SCHOLAR GOOGLE and SCOPUS to identify all articles using the following keywords: “tributyltin”, “apoptosis”, “mammals”, “mammalian cells”, “eukaryotic cells”, “rodents”, “rats”, “mice”, “in vivo” for all data published until September 2023. Two independent reviewers (LVBC and DAR) screened all manuscripts, and no relevant studies were excluded.

Eligibility criteria

In this study, several eligibility criteria were followed to identify all relevant studies. Thus, the following types of manuscripts were included: (i) all types of experimental studies, (ii) all studies reporting apoptotic effects of TBT in mammalian cells in vivo. Review articles, editorials, comments, in vitro or ex vivo studies, and letters to the editor were excluded from the analysis.

Data extraction

Data collection was conducted using a specific data collection form. The following information was recorded: study year, study design, origin, number of individuals, apoptosis assays, species used, methodological parameters, negative and positive control groups, statistical analysis, main results and conclusion.

Results

Study selection

After screening the manuscript, the full texts of the remaining 16 studies were sought and thoroughly read by the two authors (LVBC and DAR).

General characteristics of the included studies

Table 1 shows some details of the included studies. First of all, four studies were conducted in Brazil [19], [20], [21], [22]. A total of two studies were conducted in South Korea [23], 24], Egypt [25], 26], India [18], 27], and Japan [28], 29]. And finally, the study by Kishta et al. [30] was conducted in Canada.

Table 1:

Variables analyzed in the studies in alphabetical order.

Authors Year Study design/species Target organs n Negative control Positive control Assay Exposure time Dose Evaluated parameters Proper statistics description
Chen et al. [31] 2011 ICR mice Thymocites n=40 n=10 Yes No Annexin v, PI and flow cytometer 28 days 0.5, 4 and 20 mg/kg Apoptotic cells Yes
Da costa et al. [19] 2019 Female Wistar rats Mammary glands n=20 n=4 Yes No Imunoblotting assay 15 days 100 ng/kg Caspase-3 Yes
Elsammak et al. [25] 2023 Male Wistar rats Thyroid glands n=21, n=5 Yes No Immunohistochemistry 30 days 5 mg/kg Caspase-3 e beclin-1 Yes
Kim et al. [23] 2008 Male ICR mice Testis n=uninformed n=3 Yes No Tunel assay Acute dose 25,50 and 100 mg/kg Apoptotic cells Yes
Kishta et al. [30] 2007 Female Sprague-Dawley rats Ovary n=6 to 9 Yes No Tunel assay 0 to 19 or 8 to 19 of pregnancy 0.25, 2.5, 10 and 20 mg/kg Apoptotic cells Yes
Lee et al. [24] 2012 Female Sprague-Dawley rats Ovary n=27 n=9 Yes No Tunel assay 7 days 1 and 10 mg/kg Apoptotic cells Yes
Merlo et al. [20] 2016 Female Wistar rats Pituitary and adrenals n=138 n=5 Yes No Immunoblotting assay 15 or 30 days 100 ng/kg Caspase-3 Yes
Mitra et al. [18] 2015 Male Wistar rats Brain cortex n=uninformed n=5 Yes No Caspase-12 and calpain fluorometric assay, western blotting and tunnel assay Acute dose 20 mg/kg Calpain, caspase-12, bcl-2, bax, caspase-3 and apoptotic cells Yes
Mitra et al. [27] 2017 Male Wistar rats Testicular tissue n=uninformed, n=5 Yes No Western blot and calpain fluorometric assay Acute dose 10, 20 and 30 mg/kg Bax, bcl-2, caspase 3 and calpain Yes
Podratz et al. [21] 2012 Female Wistar rats Ovary n=20 n=5 Yes No Hematoxylin and eosin staining 16 days 100 ng/kg Apoptotic cells and bcl-2 e bax Yes
Sakr et al. [26] 2021 Male Wistar rats Brain cortex n=30 n=6 Yes No Immunohistochemistry 28 days 10 mg/kg Caspase-3, bax and bcl-2 Yes
Sena et al. [22] 2017 Female Wistar rats Ovary n=114 n=4 Yes No Tunel assay 15 days 100 ng/kg Apoptotic cells Yes
Tomiyama et al. [28] 2010 Male Wistar rats Olfactory bulb n=18 n=6 Yes No Tunel assay Acute dose 2.5 mg/kg Apoptotic cells Yes
Zhang et al. [32] 2012 Male ICR mice Liver n=20 n=3 Yes No Tunel assay, western blot 4 days 10, 20 and 60 mg/kg Apoptotic cells, bcl-2 and bax Yes
Zuo et al. [33] 2014 KM male mice Pancreas n=32 n=3 Yes Yes Tunel assay 45 or 60 days 0.5, 5 and 50 μg/kg Apoptotic cells Yes
Ueno et al. [29] 2009 Male ICR mice Lymphocytes n=uninformed n=4 Yes Yes Annexin v, flow cytometer Acute dose 63 mg/kg Apoptotic cells Yes

Regarding the species used in the 16 studies, the Wistar rat strain was utilized in nine studies [18], [19], [20], [21], [22, [25], [26], [27], [28]. ICR mice were used in four studies [23], 29], 31], 32]. Two studies were conducted with Sprague-Dawley rats [24], 30], and finally, KM mice were used in the study conducted by Zuo et al. [33].

Regarding the sex of the animals used, six studies were carried out using female [19], [20], [21], [22, 24], 30] and nine studies used male [18], 23], [25], [26], [27], [28], [29, 32], 33]. However, the study of Chen et al. [31] did not identify the sex of the ICR mice used.

Variables related to apoptosis

All the parameters and variables evaluated in the studies are shown in Table 2. First of all, it is important to emphasize that all authors reported the number of animals in their respective studies, and all selected studies had a negative control compared to the baseline. However, only two studies had a positive control [29], 33].

Table 2:

Main findings of studies in alphabetical order.

Authors Main findings
Chen et al. [31] ↑ apoptotic thymocytes
Da costa et al. [19] ↑ caspase-3 expression in mammary gland
Elsammak et al. [25] ↑ caspase-3 reaction and Beclin-1 in the nuclei of thyroid follicular cells
Kim et al. [23] ↑ apoptotic cells and tubules in the testes
Kishta et al. [30] ↑ apoptotic cells in fetal ovaries
Lee et al. [24] ↑ apoptotic follicles
Merlo et al. [20] ↑ caspase-3 expression in the pituitary and adrenal glands
Mitra et al. [18] ↑ apoptotic cells in the cerebral cortex, the calpain and caspase-3 and 12 activities
Mitra et al. [27] ↑ Bax, caspase-3 and calpain and ↓ caspase-8 and Bcl-2
Podratz et al. [21] ↑ apoptotic cells in the corpus luteum, granulosa cell layer, and antral space
Sakr et al. [26] ↑ positive reaction of caspase-3 and Bax and ↓ Bcl-2 in the cerebral cortex
Sena et al. [22] ↑ apoptotic cells
Tomiyama et al. [28] ↑ apoptotic cells in glomerular layer, granule cell layer, and mitral cell layer in the olfactory bulb
Zhang et al. [32] ↑ apoptotic cells and ↓ Bcl-2 expression
Zuo et al. [33] ↑ apoptotic cells in islets and acinar cells
Ueno et al. [29] No apoptotic effect on lymphocytes

The description of blind analysis was not described in any study. The analyzed studies did not have any additional experimental conditions beyond apoptosis. Consequently, all authors appropriately have described the statistical analysis used in these studies.

The authors evaluated apoptosis in mammalian cells in vivo using different methodologies. TUNEL assay was performed in six studies [22], [23], [24, 28], 30], 33]. Immunohistochemistry, immunoblotting assay and flow cytometer were performed in some studies [19], 20], 25], 26], 29], 31]. Podratz et al. [21] used hematoxylin-eosin staining (HE) as a putative methodology for detecting apoptotic cells. Three studies used more than one technique [18], 27], 32]. Mitra et al. [18] used caspase-12 and calpain fluorometric assay, western blotting and TUNEL assay. Mitra et al. [27] used western blotting and calpain fluorometric assay. Finally, Zhang et al. [32] used TUNEL assay and western blotting.

Several organs and cells were analyzed in the studies. A total of four studies assessed the ovaries [21], 22], 24], 30]. The brain cortex was evaluated by Mitra et al. [18] and Sakr et al. [26]. The testicular tissue was analyzed by Kim et al. [23] and Mitra et al. [27]. Thymocytes were analyzed by Chen et al. [31]. Lymphocytes were analyzed by Ueno et al. [29]. Da Costa et al. [19] examined the mammary glands. The thyroid glands were investigated by Elsammak et al. [25]. The olfactory bulb and liver were investigated by Tomiyama et al. [28] and Zhang et al. [32], respectively. Finally, Merlo et al. [20] investigated the effects of apoptosis on the pituitary and adrenal glands in rats.

Main results

Several studies in the scientific literature have assessed the apoptotic effect of TBT on mammalian cells in vivo in different tissues and organs. These studies have demonstrated increases in apoptotic parameters such as increase in apoptotic cells in different tissues and organs and alterations of expressions in the apoptotic proteins.

In tissues, the study of Chen et al. [31] exposed ICR mice to TBT at doses of 0.5, 4 and 20 mg/kg by gavage for 28 days, increasing the number of apoptotic thymocytes. A dose-dependent increase in thymocyte apoptosis was observed for 4 and 20 mg/kg of TBT. In another study, Ueno et al. [29] exposed male ICR mice to 63 mg/kg of TBT and evaluated if after 6 h using annexin V staining, but no apoptotic effect was observed on lymphocytes.

Regarding the organs, studies have shown an increase in apoptotic cells in the ovaries [21], 22], 24], 30]. Kishta et al. [30] have demonstrated that TBT exposure for 30 days increased the number of apoptotic cells in fetal ovaries. Lee et al. [24] showed that TBT exposure increased the number of apoptotic cells in the ovaries of Sprague-Dawley rats exposed to 10 mg/kg. Sena et al. [22] also found an increase in apoptotic follicles in the ovaries of female Wistar rats treated with 100 ng/kg by gavage. Finally, the study by Podratz et al. [21] observed an increase in apoptotic cells in the corpus luteum, the granulosa cell layer as well as in the antral space in Wistar rats treated with 100 ng/kg of TBT for 16 days.

In pancreas, Zuo et al. [33] demonstrated an increase in apoptotic cells in the islet and acinar cells of male KM mice exposed to 0.5, 5 and 50 mg/kg of TBT once every three days for 45 days. In the brain, the Tomiyama et al. [28] showed an increase in apoptotic cells in the glomerular layer, granule cell layer and mitral cell layer in the olfactory bulb of male Wistar rats exposed to an intraperitoneal single dose of 2.5 mg/kg TBT. Finally, in the testes, Kim et al. [23] observed an increase in apoptotic cells and tubules of male ICR mice treated with 25, 50 and 100 mg/kg TBT.

Regarding the expression of apoptotic proteins, the study of Da Costa et al. [19] found that TBT exposure increased the expression of caspase-3 in mammary glands of adult female Wistar rats exposed to 100 mg/kg for 15 and 30 days. Elsammak et al. [25] observed an increase in positive caspase-3 reactions in the nuclei of follicular cells in the thyroid of adult male Wistar rats treated with 5 mg/kg for 30 days.

The study of Mitra et al. [18] investigated the effect of TBT for 30 days and observed an increase in apoptotic cells, as well as increased activity of calpain, caspase-3 and 12 in the brain cortex of male Wistar rats treated with 20 mg/kg. In addition, the same authors [18] found an increased expression of bax, calpain and caspase-3 and a decreased expression of bcl2 and caspase-8 in the testicular tissue in male Wistar rats that were orally administered with a single dose of TBT (10, 20 and 30 mg/kg) and sacrificed on days 3 and 7, respectively. Sakr et al. [26] found an increase in positive caspase-3 and bax reactions and a decrease in bcl2 in the brain cortex of male Wistar rats treated with 10 mg/kg of TBT for 28 days. Finally, Zhang et al. [32] found an increase in apoptotic cells followed by decreasing bcl-2 expression in the liver of male ICR mice that were administered 60 mg/kg of TBT for four consecutive days.

Discussion

In the present review we have demonstrated that TBT exposure in different mammalian tissues in vivo induces apoptosis. For this, different techniques were used to evaluate apoptotic parameters such as the number of apoptotic cells as well as the expression of anti and proapoptotic proteins.

The TUNEL assay (TdT-mediated dUTP nick end labeling) is a method that evaluates DNA fragmentation in situ to identify cells that have undergone apoptosis. The technique consists in marking the ends of the DNA undergoing degradation with the terminal polymerase deoxynucleotidyl transferase (TdT). TdT is an enzyme that acts by catalyzing the independent addition of the deoxynucleotide triphosphate template to the 3′OH ends of DNA [34]. This technique can be visualized using immunohistochemical methods (Kyrylkova, 2012). In this study, the TUNEL assay was the most used method to assess the apoptotic effect of TBT in exposed tissues. After examining the scientific literature, it was possible to observe that most studies (8) showed positivity for apoptosis in different mammalian tissues exposed to TBT such as ovaries, testes, liver, pancreas and nervous tissue. Although it is the most sensitive technique to detect apoptosis in the phase prior to the emergence of internucleossomal DNA fragmentation, the TUNEL assay also detects DNA fragmentation from necrotic cells, what indicates the need for complementary techniques to avoid false positives [35].

Other technique used to evaluate apoptosis is flow cytometry. A total of two studies evaluated apoptotic effects on immune system cells using this method. Chen et al. [31] reported an increase in apoptotic thymocytes whereas Ueno et al. [29] did not observe any apoptotic effect in lymphocytes exposed with TBT. Flow cytometry can also be used to evaluate the number of apoptotic cells, cell viability, caspases activity, DNA cleavage, viability dyes, among other parameters that may the apoptotic process. One of the main advantages of using this method is its high cell throughput, as it can measure thousands of cells in a few seconds [36].

The review identified that tissues from the female and male reproductive systems were investigated in six studies, with the ovaries being the main targets investigated (4 out of 6). TBT exposure induced an increase in apoptotic cells in ovaries of fetuses [30], adult [22] as well as in ovarian follicles by TUNEL assay [24]. Additionally, the study of Podratz et al. [21] observed an increase in apoptotic cells in the corpus luteum, granulosa cell layer as well as in the antral space when assessed by hematoxylin and eosin staining. In the testes, Kim et al. [23] observed an increase in apoptotic cells whereas Mitra et al. [18] showed an increased in apoptotic proteins such as caspase 3, bax and calpain and a decrease in caspase 8 and antiapoptotic protein bcl-2. In reproductive organs, apoptosis is an essential component of function and development by acting on quality control mechanisms. Therefore, disruption of ovarian and testicular homeostasis induced by toxicological insults has been associated with increased infertility [37], 38].

The nervous system has been investigated in four studies. Mitra et al. [18] observed an increase in apoptotic cells in the brain cortex of rats as well as increased expression of apoptotic proteins such as calpain, caspases 3 e 12. Tomiyama et al. [28] observed an increase in apoptotic cells in the olfactory bulb of rats whereas Sakr et al. [26] demonstrated an increase in caspase 3 and bax positivity and a decrease in bcl-2 in the brain cortex of Wistar rats. Meanwhile, Merlo et al. [20] demonstrated increase in caspase 3 in both the pituitary and adrenal glands by immunoblotting. Increased apoptosis in nervous tissue is related to a increase tissue damage in addition to being present in numerous important neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases [39].

The effect of TBT on the mammary glands and liver has also been demonstrated. Da Costa et al. [19] observed that TBT exposure induced an increase in caspase 3 expression in mammary glands when evaluated in Wistar rats exposed for 15 days when investigated by immunoblotting. Similarly, Elsammak et al. [25] reported an increase in caspase 3 positivity in the follicular nuclei of thyroid cells. Caspases are proteases synthesized as zymogens that, when activated, have a cysteine residue in their active site and an aspartate residue in the substrate cleavage site. Initiator caspases (8, 9 and 10) are activated in response to an apoptotic stimulus. Consequently, effector caspases (3, 6 and 7) are important for dismantling vital cellular components [40]. Caspase 3 is the main enzyme that executes the intrinsic (or mitochondrial) and extrinsic pathway of apoptosis and is therefore and important hallmark for apoptosis [41].

The present studies in this review indicate a significant role for calpains and caspases in the apoptotic mechanism of TBT in vivo. Calpains are proenzymes existing in the cytosol which are activated when there is an increase in intracellular free Ca2+, which causes its transformation from inactive form to active form, inducing the hydrolysis of their substrates in the cytosol, nucleus and membrane, thus inducing apoptosis [41]. This pathway is called endoplasmic reticulum stress (ERS) – induced apoptosis and involves the participation of caspase 12, 9, and consequently caspase 3 in the execution of apoptosis [42]. TBT can also induce apoptosis through the intrinsic or mitochondrial pathway. In this way, caspase 9 is also essential. This enzyme is present in its inactive form in the cytosol until it is activated by an apoptotic stimulus such as the presence of cytochrome c [43]. The release of cytochrome c acts as an apoptotic stimulus in the intrinsic pathway by activating caspase 3 mediated by caspase 9 that leads to cell death [40].

The bcl-2 family proteins also play an important role in the regulation of apoptosis. They are divided into anti-apoptotic protein such as bcl-2 and proapoptotic proteins such as bax and bak. Bax and bak acts by forming pores in the mitochondrial membrane that contribute for releasing cytochrome c into the cytosol [44]. This sequestration carried out by bcl-2 has an inhibitory effect on the formation of pores with consequent inhibition of apoptosis. Therefore, bcl-2 inhibition has a proapoptotic effect, since there is an imbalance in the bcl-2/bax ratio favoring apoptosis [45]. Although in vivo studies have not studied cytochrome c release, in vitro studies demonstrate that TBT can decrease mitochondrial membrane potential and release cytochrome c into cytosol [46], 47].

The study of Elsammak et al. [25] evaluated the effect of TBT on the beclin-1 enzyme and noted a low positivity of beclin-1 in thyroid follicular cell nuclei. Although it acts mainly on autophagy, the activation of this enzyme is related to the sequestration of antiapoptotic bcl-2 members such as bcl-2 e bcl-lx followed by the release of cytochrome c and subsequent activation of caspase 3 [48].

Furthermore, TBT is a compound with a high apoptotic potential, since it affected apoptotic parameters at doses as low as 100 ng/kg of TBT for 15 days of exposure [19], 22], (Da Costa et al.; Merlo et al. [20]; Sena et al.) and dose as high as 100 mg/g in an acute dose [23]. The exposure period was also variable, since acute studies to studies that exposed 45 and 60 days of exposure [33] observed apoptotic effects in the parameters assessed.

In summary, it was possible to demonstrate in this review that TBT exposure in mammalian tissue in vivo induces apoptosis. TBT is capable to activate proapoptotic proteins such as calpain, caspases, bax and beclin-1. TBT alters the ratio of bcl-2/bax bcl-2 family proteins which favor apoptosis (Figure 1). The activation of enzymes such as calpain can induce apoptosis mediated by ERS and caspases through the intrinsic apoptosis pathway. Both pathways can activate caspase 3 mediated by caspase 9, which ultimately cleave nuclear DNA initiating apoptosis (Figure 1).

Figure 1: Tributyltin induces apoptosis in mammalian cells as a result of caspases activation, bcl-2 family deregulation and endoplasmic reticulum stress.
Figure 1:

Tributyltin induces apoptosis in mammalian cells as a result of caspases activation, bcl-2 family deregulation and endoplasmic reticulum stress.

Corresponding author: Prof. Daniel Araki Ribeiro, Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, UNIFESP, Rua Silva Jardim, 136, Room 332, Vila Mathias, Santos 11050-020, SP, Brazil, E-mail:

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: None.

  5. Research funding: None.

  6. Data availability: These data are available upon request.

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Received: 2024-01-24
Accepted: 2024-05-03
Published Online: 2024-08-06
Published in Print: 2025-03-26

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Mercury and cadmium-induced inflammatory cytokines activation and its effect on the risk of preeclampsia: a review
  4. Prevalence of chronic obstructive pulmonary disease in Indian nonsmokers: a systematic review & meta-analysis
  5. Beyond the outdoors: indoor air quality guidelines and standards – challenges, inequalities, and the path forward
  6. Cadmium exposure and thyroid hormone disruption: a systematic review and meta-analysis
  7. New generation sequencing: molecular approaches for the detection and monitoring of bioaerosols in an indoor environment: a systematic review
  8. Concentration of Tetrabromobisphenol-A in fish: systematic review and meta-analysis and probabilistic health risk assessment
  9. The association between indoor air pollution from solid fuels and cognitive impairment: a systematic review and meta-analysis
  10. Phthalates and uterine disorders
  11. Effectiveness of educational interventions for the prevention of lead poisoning in children: a systematic review
  12. Association between exposure to per- and polyfluoroalkyl substances and levels of lipid profile based on human studies
  13. Summary of seven Swedish case reports on the microwave syndrome associated with 5G radiofrequency radiation
  14. Expanding the focus of the One Health concept: links between the Earth-system processes of the planetary boundaries framework and antibiotic resistance
  15. Exploring the link between ambient PM2.5 concentrations and respiratory diseases in the elderly: a study in the Muang district of Khon Kaen, Thailand
  16. Standards for levels of lead in soil and dust around the world
  17. Tributyltin induces apoptosis in mammalian cells in vivo: a scoping review
  18. The influence of geology on the quality of groundwater for domestic use: a Kenyan review
  19. Biological concentrations of DDT metabolites and breast cancer risk: an updated systematic review and meta-analysis
  20. Letter to the Editor
  21. Ancient medicine and famous iranian physicians
https://doi.org/10.1515/reveh-2023-0152
Keywords for this article
TBT; apoptosis; mammalian cells; in vivo; ERS; intrinsic pathway

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Mercury and cadmium-induced inflammatory cytokines activation and its effect on the risk of preeclampsia: a review
  4. Prevalence of chronic obstructive pulmonary disease in Indian nonsmokers: a systematic review & meta-analysis
  5. Beyond the outdoors: indoor air quality guidelines and standards – challenges, inequalities, and the path forward
  6. Cadmium exposure and thyroid hormone disruption: a systematic review and meta-analysis
  7. New generation sequencing: molecular approaches for the detection and monitoring of bioaerosols in an indoor environment: a systematic review
  8. Concentration of Tetrabromobisphenol-A in fish: systematic review and meta-analysis and probabilistic health risk assessment
  9. The association between indoor air pollution from solid fuels and cognitive impairment: a systematic review and meta-analysis
  10. Phthalates and uterine disorders
  11. Effectiveness of educational interventions for the prevention of lead poisoning in children: a systematic review
  12. Association between exposure to per- and polyfluoroalkyl substances and levels of lipid profile based on human studies
  13. Summary of seven Swedish case reports on the microwave syndrome associated with 5G radiofrequency radiation
  14. Expanding the focus of the One Health concept: links between the Earth-system processes of the planetary boundaries framework and antibiotic resistance
  15. Exploring the link between ambient PM2.5 concentrations and respiratory diseases in the elderly: a study in the Muang district of Khon Kaen, Thailand
  16. Standards for levels of lead in soil and dust around the world
  17. Tributyltin induces apoptosis in mammalian cells in vivo: a scoping review
  18. The influence of geology on the quality of groundwater for domestic use: a Kenyan review
  19. Biological concentrations of DDT metabolites and breast cancer risk: an updated systematic review and meta-analysis
  20. Letter to the Editor
  21. Ancient medicine and famous iranian physicians
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