Kolaviron ameliorates hepatic and renal dysfunction associated with multiwalled carbon nanotubes in rats

Awogbindin, Ifeoluwa O.; Maduako, Ikenna C.; Adedara, Isaac A.; Owumi, Solomon E.; Ajeleti, Akinola O.; Owoeye, Olatunde; Patlolla, Anita K.; Tchounwou, Paul B.; Farombi, Ebenezer O.

doi:10.1002/tox.23011

Cited by 8 publications

(3 citation statements)

References 48 publications

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“…The wide application of MWCNTs in various fields has raised enormous concerns regarding their health risks for humans. Although the toxicity of MWCNTs had been investigated by numerous studies, most of literatures explored the influence on the inner organs (such as lung, 28 , 29 liver, kidney, 30 brain 31 or reproductive systems). 32 The eye toxicity of MWCNTs was relatively ignored.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Genes Associated with Pristine Multi-Walled Carbon Nanotubes-Induced Toxicity in Ocular Cells

Luo¹,

Xie²,

Su³

et al. 2023

IJN

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Background The wide application of multi-walled carbon nanotubes (MWCNTs) in various fields has raised enormous concerns regarding their safety for humans. However, studies on the toxicity of MWCNTs to the eye are rare and potential molecular mechanisms are completely lacking. This study was to evaluate the adverse effects and toxic mechanisms of MWCNTs on human ocular cells. Methods Human retinal pigment epithelial cells (ARPE-19) were treated with pristine MWCNTs (7–11 nm) (0, 25, 50, 100 or 200 μg/mL) for 24 hours. MWCNTs uptake into ARPE-19 cells was examined using transmission electron microscopy (TEM). The cytotoxicity was evaluated by CCK-8 assay. The death cells were detected by Annexin V-FITC/PI assay. RNA profiles in MWCNT-exposed and non-exposed cells (n = 3) were analyzed using RNA-sequencing. The differentially expressed genes (DEGs) were identified through the DESeq2 method and hub of which were filtered by weighted gene co-expression, protein–protein interaction (PPI) and lncRNA-mRNA co-expression network analyses. The mRNA and protein expression levels of crucial genes were verified using quantitative polymerase chain reaction (qPCR), colorimetric analysis, ELISA and Western blotting. The toxicity and mechanisms of MWCNTs were also validated in human corneal epithelial cells (HCE-T). Results TEM analysis indicated the internalization of MWCNTs into ARPE-19 cells to cause cell damage. Compared with untreated ARPE-19 cells, those exposed to MWCNTs exhibited significantly decreased cell viabilities in a dose-dependent manner. The percentages of apoptotic (early, Annexin V positive; late, Annexin V and PI positive) and necrotic (PI positive) cells were significantly increased after exposure to IC50 concentration (100 μg/mL). A total of 703 genes were identified as DEGs; 254 and 56 of them were, respectively, included in darkorange2 and brown1 modules that were significantly associated with MWCNT exposure. Inflammation-related genes (including CXCL8, MMP1, CASP3, FOS, CXCL2 and IL11 ) were screened as hub genes by calculating the topological characteristics of genes in the PPI network. Two dysregulated long non-coding RNAs ( LUCAT1 and SCAT8 ) were shown to regulate these inflammation-related genes in the co-expression network. The mRNA levels of all eight genes were confirmed to be upregulated, while caspase-3 activity and the release of CXCL8, MMP1, CXCL2, IL11 and FOS proteins were demonstrated to be increased in MWCNT-treated ARPE-19 cells. MWCNTs exposure also can induce cytotoxicity and increase the caspase-3 activity and the expression of LUCAT1, MMP1, CXCL2, and IL11 mRNA and protein in HCE-T cells. Conclusion Our study provides promising biomarkers for monitoring MWCNT-induced eye disorders and targets for developing preventive and therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Genes Associated with Pristine Multi-Walled Carbon Nanotubes-Induced Toxicity in Ocular Cells

Luo¹,

Xie²,

Su³

et al. 2023

IJN

View full text Add to dashboard Cite

show abstract

“…Tissue-specific levels of proinflammatory markers were also assessed. Urea and creatinine levels were reduced, and myeloperoxidase activity, nitric oxide level, reactive oxygen and nitrogen species, and tumor necrosis factor level in kidneys were increased [ 92 ]. Guzmán-Mendoza et al took pristine, pre, and functionalized carbon nanotubes under investigation.…”

Section: Nephrotoxicitymentioning

confidence: 99%

Assessment of Pristine Carbon Nanotubes Toxicity in Rodent Models

Witkowska

Florek

Mrówczyński

2022

IJMS

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Carbon nanotubes are increasingly used in nanomedicine and material chemistry research, mostly because of their small size over a large surface area. Due to their properties, they are very attractive candidates for use in medicine and as drug carriers, contrast agents, biological platforms, and so forth. Carbon nanotubes (CNTs) may affect many organs, directly or indirectly, so there is a need for toxic effects evaluation. The main mechanisms of toxicity include oxidative stress, inflammation, the ability to damage DNA and cell membrane, as well as necrosis and apoptosis. The research concerning CNTs focuses on different animal models, functionalization, ways of administration, concentrations, times of exposure, and a variety of properties, which have a significant effect on toxicity. The impact of pristine CNTs on toxicity in rodent models is being increasingly studied. However, it is immensely difficult to compare obtained results since there are no standardized tests. This review summarizes the toxicity issues of pristine CNTs in rodent models, as they are often the preferred model for human disease studies, in different organ systems, while considering the various factors that affect them. Regardless, the results showed that the majority of toxicological studies using rodent models revealed some toxic effects. Even with different properties, carbon nanotubes were able to generate inflammation, fibrosis, or biochemical changes in different organs. The problem is that there are only a small amount of long-term toxicity studies, which makes it impossible to obtain a good understanding of later effects. This article will give a greater overview of the situation on toxicity in many organs. It will allow researchers to look at the toxicity of carbon nanotubes in a broader context and help to identify studies that are missing to properly assess toxicity.

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“…2,3 This unique nanoscale structure offers CNTs superior properties suitable for drug delivery, including high drug loading capacity 4 and excellent cellular uptake. 5 However, concerns have emerged regarding the toxicity of CNTs as numerous toxicological studies have identified that CNTs can elicit a pathogenic response, including hepatotoxicity, 6 inhibition of cytochrome P450s (CYP450s), 7 nephrotoxicity, 8 pulmonary fibrosis 9 and immunotoxicity. 10 Furthermore, CNTs have a similar structure to asbestos fibers, and MWCNT-7 (long, rigid CNT) has been classified as possibly carcinogenic to humans (Group 2B) 11 following studies showing that intraperitoneal injection of MWCNTs caused mesothelioma in rodents.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Intravenous Administration of Carbon Nano-Onions is Non-Toxic in Female Mice

Tan¹,

Thomsen²,

Shrestha³

et al. 2023

IJN

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Background: A nanoscale drug carrier could have a variety of therapeutic and diagnostic uses provided that the carrier is biocompatible in vivo. Carbon nano-onions (CNOs) have shown promising results as a nanocarrier for drug delivery. However, the systemic effect of CNOs in rodents is unknown. Therefore, we investigated the toxicity of CNOs following intravenous administration in female BALB/c mice. Results: Single or repeated administration of oxi-CNOs (125, 250 or 500 µg) did not affect mouse behavior or organ weight and there was also no evidence of hepatotoxicity or nephrotoxicity. Histological examination of organ slices revealed a significant dosedependent accumulation of CNO aggregates in the spleen, liver and lungs (p<0.05, ANOVA), with a trace amount of aggregates appearing in the kidneys. However, CNO aggregates in the liver did not affect CYP450 enzymes, as total hepatic CYP450 as well as CYP3A catalytic activity, as meased by erythromycin N-demethylation, and protein levels showed no significant changes between the treatment groups compared to vehicle control. CNOs also failed to act as competitive inhibitors of CYP3A in vitro in both mouse and human liver microsomes. Furthermore, CNOs did not cause oxidative stress, as indicated by the unchanged malondialdehyde levels and superoxide dismutase activity in liver microsomes and organ homogenates. Conclusion:This study provides the first evidence that short-term intravenous administration of oxi-CNOs is non-toxic to female mice and thus could be a promising novel and safe drug carrier.

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Kolaviron ameliorates hepatic and renal dysfunction associated with multiwalled carbon nanotubes in rats

Cited by 8 publications

References 48 publications

Inflammatory Genes Associated with Pristine Multi-Walled Carbon Nanotubes-Induced Toxicity in Ocular Cells

Inflammatory Genes Associated with Pristine Multi-Walled Carbon Nanotubes-Induced Toxicity in Ocular Cells

Assessment of Pristine Carbon Nanotubes Toxicity in Rodent Models

Short-Term Intravenous Administration of Carbon Nano-Onions is Non-Toxic in Female Mice

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