The Toxic Effects and Mechanisms of Nano-Cu on the Spleen of Rats

Zhou, Xiong; Zhao, Ling; Luo, Jie; Tang, Huaqiao; Xu, Min; Wang, Yanyan; Yang, Xiaoyu; Chen, Helin; Li, Yinglun; Ye, Gang; Shi, Fei; Lü, Cheng; Jing, Bo

doi:10.3390/ijms20061469

Cited by 54 publications

(28 citation statements)

References 37 publications

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“…To our knowledge, the effects of nanoCu enriched BC on its biocompatibility and cytotoxicity have not been extensively studied. The acute toxicity of nanoCu was reported to damage the liver, the kidney, and the spleen [69,70], and the use of nanoCu beyond the safety limits (depending on many factors) would lead to severe cytotoxicity [71,72]. With regards to the cytocompatibility, the data on biopolymers containing Cu are scarce.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Activity and Cytocompatibility of Bone Cement Enriched with Antibiotic, Nanosilver, and Nanocopper for Bone Regeneration

et al. 2019

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Bacterial infections due to bone replacement surgeries require modifications of bone cement with antibacterial components. This study aimed to investigate whether the incorporation of gentamicin or nanometals into bone cement may reduce and to what extent bacterial growth without the loss of overall cytocompatibility and adverse effects in vitro. The bone cement Cemex was used as the base material, modified either with gentamicin sulfate or nanometals: Silver or copper. The inhibition of bacterial adhesion and growth was examined against five different bacterial strains along with integrity of erythrocytes, viability of blood platelets, and dental pulp stem cells. Bone cement modified with nanoAg or nanoCu revealed greater bactericidal effects and prevented the biofilm formation better compared to antibiotic-loaded bone cement. The cement containing nanoAg displayed good cytocompatibility without noticeable hemolysis of erythrocytes or blood platelet disfunction and good viability of dental pulp stem cells (DPSC). On the contrary, the nanoCu cement enhanced hemolysis of erythrocytes, reduced the platelets aggregation, and decreased DPSC viability. Based on these studies, we suggest the modification of bone cement with nanoAg may be a good strategy to provide improved implant fixative for bone regeneration purposes.

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Section: Discussionmentioning

confidence: 99%

Antibacterial Activity and Cytocompatibility of Bone Cement Enriched with Antibiotic, Nanosilver, and Nanocopper for Bone Regeneration

et al. 2019

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“…24 The accumulation of free radicals can also damage intracellular DNA, and 8-OHdG is the most commonly used biomarker in the oxidative damage of DNA. 25 The results showed that SOD and GSH-Px activities in spleen tissue of the MOD group were significantly decreased in comparison to the CON group (P<0.05, P<0.01) ( Figure 6A and B). Anwulignan increased SOD activity (P<0.01, P<0 05).…”

Section: Anwulignan Increased Sod and Gsh-px Activities And Decreasedmentioning

confidence: 88%

<p>Regulatory Effect of Anwulignan on the Immune Function Through Its Antioxidation and Anti-Apoptosis in D-Galactose-Induced Aging Mice</p>

Gao

et al. 2020

CIA

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Background: Aging is a spontaneous and inevitable phenomenon of biology, which can lead to the gradual deterioration of tissues and organs. One of the age-related deterioration processes is immunosenescence, which leads to changes in the function of immune systems, including immune cells and associated cytokines. A proper modulation of immune responses can improve the age-related immunosenescence process and then reach healthy aging. Schisandra sphenanthera, a traditional Chinese medicine, has been used as both a medicine and a nutritional supplement for thousands of years. Anwulignan, a monomer compound of Schisandra sphenanthera lignans, has been reported to possess an immunomodulatory effect. Therefore, this study was designed to further explore whether Anwulignan could also modulate the immune functions in aging model mice and the underlying mechanism. Methods: D-galactose (D-gal) is often used as an inducer of immunosenescence in animals. In this study, a mice model was created by subcutaneous D-gal (220 mg kg −1) for successive 42 days. Then, the blood and spleen tissue samples were taken for the analysis and observation of cytokine levels, immunoglobulin levels, leukocyte numbers, and the phagocytic activity of macrophages, as well as the histological changes, the proliferation ability of lymphocytes, and the biochemical parameters in the spleen tissue. Results: Anwulignan significantly increased the serum levels of IL-2, IL-4, IFN-γ, lgG, lgM, and lgA, decreased the content of TNF-α and IL-6 in the aging mice, and increased the blood leukocyte number, the phagocytic activity, the lymphocyte proliferation, and the spleen index in vitro. Anwulignan also significantly increased the activities of SOD and GSH-Px, decreased the contents of MDA and 8-OHdG in the spleen tissue, up-regulated the expressions of Nrf2, HO-1, and Bcl2, down-regulated the expressions of Keap1, Caspase-3, and Bax in the spleen cells, and reduced the apoptosis of spleen lymphocytes. Conclusion: Anwulignan can restore the immune function that is declined in D-gal-induced aging mice partly related to its antioxidant capacity by activating the Nrf2/ARE pathway and downstream enzymes, as well as its anti-apoptotic effect by regulating Caspase-3 and the ratio of Bcl2 to Bax in the spleen.

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“…MAPK signals are upstream of multiple stress-stimulation cascade events. 32 , 33 Oxidative damage can activate MAPK14 phosphorylation, 21 which in turn promotes the separation of Nrf2 from Keap1. 27 Nrf2 then translocates to the nucleus and binds to antioxidant response elements to activate various related genes, such as HO-1 and NQO1 .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have mainly focused on the cytotoxicity of CuNPs in the liver, 19 kidney, 20 and spleen. 21 However, the ovary has recently been reported to be a target organ for CuNP toxicity. Our previous studies show that CuNPs can migrate to the ovaries of rats and accumulate in large quantities, thereby causing various types of damage such as ovarian injury, follicular atresia, oxidative stress, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies

Zou¹,

Cheng²,

Xu³

et al. 2021

IJN

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Purpose The toxicity of copper nanoparticle (CuNP) exposure in the ovaries has attracted attention recently, but the precise molecular mechanism involved requires further investigation. We investigated the cytotoxicity of CuNPs in ovarian granulosa cells and the protective effect of heme oxygenase 1 (HO-1) against CuNP-induced damage. Methods Human ovarian granulosa cells (COV434) were treated with CuNPs, and cytotoxicity was evaluated using Cell Counting Kit-8 and flow cytometry assays. Oxidative stress was identified using biochemical markers of oxidation and anti-oxidation. The protein levels of mitogen-activated protein kinase 14 (MAPK14), phospho-MAPK14, nuclear factor erythroid 2-related factor 2 (Nrf2), and HO-1 were measured by immunoblotting. Subsequently, for oxidative stress parameter detection, the cells were pre-treated with hemin to induce HO-1 expression prior to CuNP treatment. Results Exposure to CuNPs decreased cell viability and the mitochondrial membrane potential, increased the apoptosis rate, and induced oxidative stress. Furthermore, hemin pretreatment induced HO-1 expression in cells, which partially reduced the accumulation of reactive oxygen species induced by CuNPs and increased the levels of antioxidant enzymes. Conclusion CuNPs exert cytotoxic effects on human ovarian granulosa cells by inducing oxidative stress, and may induce HO-1 expression via the MAPK14-Nrf2 signaling pathway. Moreover, HO-1 protects against oxidative stress induced by CuNPs.

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The Toxic Effects and Mechanisms of Nano-Cu on the Spleen of Rats

Cited by 54 publications

References 37 publications

Antibacterial Activity and Cytocompatibility of Bone Cement Enriched with Antibiotic, Nanosilver, and Nanocopper for Bone Regeneration

Antibacterial Activity and Cytocompatibility of Bone Cement Enriched with Antibiotic, Nanosilver, and Nanocopper for Bone Regeneration

<p>Regulatory Effect of Anwulignan on the Immune Function Through Its Antioxidation and Anti-Apoptosis in D-Galactose-Induced Aging Mice</p>

Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies

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