Amelioration of titanium dioxide nanoparticles-induced liver injury in mice: Possible role of some antioxidants

Azim, Samy A. Abdel; Darwish, Hebatallah A.; Rizk, Maha Z.; Ali, Sanaa A.; Kadry, Mai O.

doi:10.1016/j.etp.2015.02.001

Cited by 66 publications

(58 citation statements)

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“…To the best of the authors' knowledge, few studies have reported the effects of TiO 2 NPs on the intestine and liver as well as the mechanism of action. [6][7][8][9] Previous studies have shown that TiO 2 NPs induce oxidative stress and inflammation in HepG2 and Caco-2 cells. [10][11][12] It has also been shown that TiO 2 NPs increase ROS, inflammation, and apoptosis in the respiratory system.…”

Section: Introductionmentioning

confidence: 99%

“…13 ROS attacks biomolecules such as DNA, proteins, lipids, and carbohydrates, which cause oxidation, methylation, deamination, apoptosis, and, consequently, lead to cell death. 14 Azim et al 7 showed that oral administration of TiO 2 NPs (150 mg/kg/day) for 2 weeks in mice markedly elevated liver enzymes, malondialdehyde (MDA) levels, and gene expressions of NF-κB and Bax in hepatic tissue. TiO 2 NPs (intraperitoneal [i.p.…”

Section: Introductionmentioning

confidence: 99%

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<p>NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study</p>

Abbasi-Oshaghi¹,

Mirzaei²,

Pourjafar³

2019

IJN

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Purpose This study evaluated the effects of titanium dioxide nanoparticles (TiO 2 NPs) on liver and intestine of normal rats. Methods Male rats were divided into four groups as follows: 1) control rats, 2) control rats that orally received 10 mg/kg TiO 2 NPs, 3) control rats that orally received 50 mg/kg TiO 2 NPs, and 4) control rats that orally received 100 mg/kg TiO 2 NPs. After 30 days, the NLRP3 inflammasome pathway (NLRP3, caspase-1, and IL-1β), antioxidant pathway (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT]), inflammatory pathway (inducible nitric oxide synthase [iNOS] and tumor necrosis factor-α [TNF-α]), and the apoptosis pathway (p53, Bax, Bcl-2, and caspase-3) were determined in the intestine and liver of the rats. H&E and Masson’s trichrome (MT) staining as well as TUNEL assay were used to examine the liver and the intestine. Biochemical factors, cytotoxicity, ROS generation, and apoptosis rate were also determined in HepG2 and Caco-2 cells. Results TiO 2 NPs in a dose-dependent manner increased cytotoxicity, oxidative stress, and apoptosis rate in Caco-2 and HepG2 cells. The administration of TiO 2 NPs significantly reduced antioxidant enzyme activity and gene expressions (SOD, CAT, and GPx) as well as glutathione (GSH) levels and total antioxidant capacity (TAC) in a dose-dependent manner. TiO 2 NPs also induced the apoptosis pathway and inflammatory pathway gene expressions and caspase-3 activity in the intestine and liver. TUNEL assay was in agreement with gene expressions. TiO 2 NPs also led to morphological changes in the liver and intestine. Conclusion TiO 2 NPs could have cytotoxic effects on the intestine and liver structure and function by inducing oxidative stress, inflammation, and apoptosis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study</p>

Abbasi-Oshaghi¹,

Mirzaei²,

Pourjafar³

2019

IJN

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“…An animal study showed that consecutive feeding of rats with TiO 2 resulted in suppression of hepatic glutathione levels and triggering of inflammatory response by activation of macrophages. This observed liver toxicity of TiO 2 was partly reversible by parallel feeding of antioxidants 58 . Repeated injections of TiO 2 NP in the peritoneum of mice resulted in severe histopathological changes and liver cell apoptosis.…”

Section: Nanomaterials Effects In Vivomentioning

confidence: 86%

Current systems biology approaches in hazard assessment of nanoparticles

Ehrhart¹,

Evelo²,

Willighagen³

2015

Preprint

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The amount of nanoparticles (NPs) in human environment is increasing. The main sources are the increased introduction in consumer products and air pollution (diesel exhaust). It is meanwhile common knowledge that NPs behave differently as bulk material because of their nano-size. This leads in general to a higher reactivity and some other changed properties, e.g. solubility, surface potential, conductivity, and, to different effects on biological systems. The main impacts of NPs on a cellular and organism level are meanwhile well known: release of toxic ions, increased oxidative stress, and inflammation. Beside these, there is increasing evidence that NPs, especially in low dose/long exposure scenarios, affect biological systems in a broader way, interact with drugs, and exacerbate the effects of diseases. To investigate these effects systems biology approaches are the method of choice. This review summarizes the state of the art of nanoparticle effects on cells and organisms and demonstrate the add value of systems biology investigations to NP hazard assessment.Abbreviations: nanoparticle (NP), carbon nanotube (CNT), single walled carbon nanotube (SWCNT), multi walled carbon nanotube (MWCNT), ADME (adsorption, distribution, metabolization, excretion), PAMAM (poly(amidoamine)), Particles of the same material source but small differences in size, surface (coating), charge or solvent components may exhibit different properties 2 . Systems biology is a holistic approach to model complex biological systems using mathematical and computer science methods. Basis of systems biology are the single components and entities of a biological system: genes, transcripts, proteins, and metabolites (see Figure 1). A good understanding and a description of the single entities and how they are interacting within a biological system is crucial for systems biology approaches. Based on this, time or incident dependent changes, e.g. exposure of NPs, in the system can be investigated. The interactions and relations between the entities are commonly described in biological pathways and networks. The state-of-art measuring technologies like genome sequencing and high throughput measurements enables the researchers to study the overall behavior and phenotype of a biological system in a defined setting. So, besides "listing the parts of an airplane" the scientific community proceeds to study the system as a whole 3 . This thorough understanding finally allows prediction of behavior using computational models. Figure 1 Scheme of systems biology. Biologic entities like genes, proteins or metabolites are connected by interactions forming the structure of the system. This structure alters with time and reacts to incidents demonstrating systems dynamics and control mechanisms.In this review we focus on the actual status of hazard assessment of NPs and the added value of using systems biology tools and methods in the assessment. We excluded NPs for therapeutical use because cost-benefit analysis for drugs is differently evaluated. NP toxicologyNP...

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“…Although a direct interaction of quinone compounds with KEAP1 Cys residues has not yet been described, indirect proof has led to the proposal that these molecules are NRF2 inducers. In addition to their antioxidant activity: (i) coenzyme Q 10 , vitamin E, idebenone, EPI-743, and MitoQ are able to increase NRF2 stability/expression and to induce NQO1 activity in cells and in animal models [77,[102][103][104][105][106], which is a renowned method to evaluate the functionality of NRF2 inducers [107]; (ii) the chemical characteristics of the para-benzoquinone moiety make these molecules able to react with thiol compounds [108] and with protein-contained cysteine residues [109]; (iii) in silico modeling analyses showed a potential interaction between the vitamin E and KEAP1 [110], suggesting a common behavior for molecules sharing the same biochemical structure; and (iv) in particular conditions, especially in an oxidative stress-induced environment [111][112][113][114], these compounds can act as pro-oxidants thus directly inducing NRF2 activity (i.e., by interacting with KEAP1) or increasing the amount of oxidative species in the cell.…”

Section: Therapeutic Intervention In the Regulation Of Nrf2-mediated mentioning

confidence: 99%

The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich’s Ataxia

Rosa

Bertini

Piemonte

2020

IJMS

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Friedreich’s ataxia (FA) is a trinucleotide repeats expansion neurodegenerative disorder, for which no cure or approved therapies are present. In most cases, GAA trinucleotide repetitions in the first intron of the FXN gene are the genetic trigger of FA, determining a strong reduction of frataxin, a mitochondrial protein involved in iron homeostasis. Frataxin depletion impairs iron–sulfur cluster biosynthesis and determines iron accumulation in the mitochondria. Mounting evidence suggests that these defects increase oxidative stress susceptibility and reactive oxygen species production in FA, where the pathologic picture is worsened by a defective regulation of the expression and signaling pathway modulation of the transcription factor NF-E2 p45-related factor 2 (NRF2), one of the fundamental mediators of the cellular antioxidant response. NRF2 protein downregulation and impairment of its nuclear translocation can compromise the adequate cellular response to the frataxin depletion-dependent redox imbalance. As NRF2 stability, expression, and activation can be modulated by diverse natural and synthetic compounds, efforts have been made in recent years to understand if regulating NRF2 signaling might ameliorate the pathologic defects in FA. Here we provide an analysis of the pharmaceutical interventions aimed at restoring the NRF2 signaling network in FA, elucidating specific biomarkers useful for monitoring therapeutic effectiveness, and developing new therapeutic tools.

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Amelioration of titanium dioxide nanoparticles-induced liver injury in mice: Possible role of some antioxidants

Cited by 66 publications

References 58 publications

<p>NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study</p>

<p>NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study</p>

Current systems biology approaches in hazard assessment of nanoparticles

The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich’s Ataxia

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