The influence of five metallic nanoparticles on the expression of major drug-metabolizing enzyme genes with correlation of inflammation in mouse livers

Jarrar, Yazun; Al‐Doaiss, Amin A.; Alfaifi, Mohammad Y.; Shati, Ali A.; Alkahtani, Mohammed Ali; Jarrar, Bashir M.

doi:10.1016/j.etap.2020.103449

Cited by 15 publications

(5 citation statements)

References 52 publications

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“…Induction of the pulmonary cyp2c29 enzyme by diclofenac may result in an increased drug metabolism in the lung. It was reported that diclofenac decreased the expression of the hepatic cyp2c29 gene, which was associated with hepatotoxicological alterations in the liver [34]. This indicated that diclofenac has a tissue-dependent effect on the mRNA expression of the cyp2c29 gene [34].…”

Section: Discussionmentioning

confidence: 95%

Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs

et al. 2022

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Paracetamol and nonsteroidal anti-inflammatory drugs are widely used in the management of respiratory viral infections. This study aimed to determine the effects of the most commonly used analgesics (paracetamol, ibuprofen, and diclofenac) on the mRNA expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and arachidonic-acid-metabolizing genes in mouse lungs. A total of twenty eight Balb/c mice were divided into four groups and treated separately with vehicle, paracetamol, ibuprofen, and diclofenac in clinically equivalent doses for 14 days. Then, the expressions of SARS-CoV-2 entry, ACE2, TMPRSS2, and Ctsl genes, in addition to the arachidonic-acid-metabolizing cyp450, cox, and alox genes, were analyzed using real-time PCR. Paracetamol increased the expressions of TMPRSS2 and Ctsl genes by 8.5 and 5.6 folds, respectively, while ibuprofen and diclofenac significantly decreased the expression of the ACE2 gene by more than 2.5 folds. In addition, all tested drugs downregulated (p < 0.05) cox2 gene expression, and paracetamol reduced the mRNA levels of cyp4a12 and 2j5. These molecular alterations in diclofenac and ibuprofen were associated with pathohistological alterations, where both analgesics induced the infiltration of inflammatory cells and airway wall thickening. It is concluded that analgesics such as paracetamol, ibuprofen, and diclofenac alter the expression of SARS-CoV-2 entry and arachidonic-acid-metabolizing genes in mouse lungs.

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Section: Discussionmentioning

confidence: 95%

Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs

et al. 2022

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“…The liver accumulation of AgNPs coated with positively charged coatings was previously reported in a fish model, accompanied by size-related inflammation and genotoxicity [ 79 , 80 ]. Toxic effects, evidenced by both liver inflammation and up-regulation of hepatotoxic markers, were reported for citrate-capped AgNPs [ 81 ]. Increased alveolar breakdown and inflammatory infiltrate were noticed after prolonged treatment with Ag@EO NPs.…”

Section: ⧉ Discussionmentioning

confidence: 99%

Biodistribution of essential oil-conjugated silver nanoparticles

Gherasim

Grumezescu²,

Mogoşanu³

et al. 2021

Rom J Morphol Embryol

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The beneficial synergy between antimicrobial silver nanoparticles (AgNPs) and essential oils (EOs), with therapeutic effects that have been acknowledged and explored for a long time, opens the way towards developing new and promising alternatives for anti-infective therapies. With the aim to improve the cytocompatibility and stability of AgNPs and to overcome the volatilization of EOs, AgNPs conjugated with sage (Salvia officinalis) and cinnamon (Cinnamomum aromaticum) EOs were obtained in our study. The synthesis process was realized either by classical or ultrasound-assisted chemical reduction. Compositional and microstructural characterization of the as-obtained Ag@EO NPs was performed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The biodistribution of Ag@EO NPs was evaluated on a mouse animal model.

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“…Liver toxicity is a pivotal concern for risk assessment of environmentally exposed MNPs, as the liver is the major organ where MNPs are deposited and metabolized. In healthy adult rodents, MNP exposure caused hepatic inflammation, oxidative stress, DNA damage, and hepatocyte apoptosis and/or necrosis [ 34 , 35 , 36 ]. The above adverse outcomes in response to MNP exposure may be further aggravated in rodent models of NAFLD [ 13 ], suggesting the susceptibility of NAFLD individuals to MNPs.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles

Zhang

Wei

Liu

et al. 2021

IJMS

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Non-alcoholic fatty liver disease (NAFLD), mainly characterized by the accumulation of excess fat in hepatocytes, is the most prevalent liver disorder afflicting ~25% of adults worldwide. In vivo studies have shown that adult rodents with NAFLD were more sensitive to metallic nanoparticles (MNPs) than healthy MNPs. However, due to the complex interactions between various cell types in a fatty liver, it has become a major challenge to reveal the toxic effects of MNPs to specific types of liver cells such as steatotic hepatocytes. In this study, we reported the susceptibility of steatotic hepatocytes in cytotoxicity and the induction of oxidative stress to direct exposures to MNPs with different components (silver, ZrO2, and TiO2 NPs) and sizes (20–30 nm and 125 nm) in an oleic acid (OA) -induced steatotic HepG2 (sHepG2) cell model. Furthermore, the inhibitory potential of MNPs against the process of fatty acid oxidation (FAO) were obvious in sHepG2 cells, even at extremely low doses of 2 or 4 μg/mL, which was not observed in non-steatotic HepG2 (nHepG2) cells. Further experiments on the differential cell uptake of MNPs in nHepG2 and sHepG2 cells demonstrated that the susceptibility of steatotic hepatocytes to MNP exposures was in association with the higher cellular accumulation of MNPs. Overall, our study demonstrated that it is necessary and urgent to take the intracellular exposure dose into consideration when assessing the potential toxicity of environmentally exposed MNPs.

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The influence of five metallic nanoparticles on the expression of major drug-metabolizing enzyme genes with correlation of inflammation in mouse livers

Cited by 15 publications

References 52 publications

Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs

Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs

Biodistribution of essential oil-conjugated silver nanoparticles

Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles

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