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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Acute Damage to the Sperm Quality and Spermatogenesis in Male Mice Exposed to Curcumin-Loaded Nanoparticles

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          Abstract

          Background

          Curcumin has shown many pharmacological activities in both preclinical and clinical studies. Many technologies have been developed and applied to improve the solubility and bioavailability of curcumin, especially the nanotechnology-based delivery systems. However, there has been evidence that certain nanoparticles have potential reproductive toxicity in practice.

          Methods

          Curcumin-poly (lactic-co-glycolic acid) (PLGA)-PEG nanoparticles (Cur-PLGA-NPs for short) were prepared. The Cur-PLGA-NPs were evaluated with its effect on the proliferation of mouse testicular cell lines in vitro and spermatogenesis in vivo, while PLGA-NPs were used as control. For animal experiments, male BALB/c mice were treated with 20 mg/kg of Cur-PLGA-NPs for continuous 10 days via tail vein injection.

          Results

          We found the curcumin nanoparticles suppressed the proliferation of testicular cell lines in vitro. Furthermore, a short-term intravenous delivery of curcumin-loaded nanoparticles could be harmful to the differentiation of spermatogonia, the elongation of spermatids, as well as the motility of mature sperms.

          Conclusion

          In the present study, we disclosed the acute damage on mouse spermatogenesis and sperm parameters by curcumin-loaded nanoparticles. Our results suggested that the reproductive toxicity of nanoformulated curcumin needs to be prudently evaluated before its application.

          Most cited references34

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          Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription.

          Acetylation of histones and non-histone proteins is an important post-translational modification involved in the regulation of gene expression in eukaryotes and all viral DNA that integrates into the human genome (e.g. the human immunodeficiency virus). Dysfunction of histone acetyltransferases (HATs) is often associated with the manifestation of several diseases. In this respect, HATs are the new potential targets for the design of therapeutics. In this study, we report that curcumin (diferuloylmethane), a major curcumanoid in the spice turmeric, is a specific inhibitor of the p300/CREB-binding protein (CBP) HAT activity but not of p300/CBP-associated factor, in vitro and in vivo. Furthermore, curcumin could also inhibit the p300-mediated acetylation of p53 in vivo. It specifically represses the p300/CBP HAT activity-dependent transcriptional activation from chromatin but not a DNA template. It is significant that curcumin could inhibit the acetylation of HIV-Tat protein in vitro by p300 as well as proliferation of the virus, as revealed by the repression in syncytia formation upon curcumin treatment in SupT1 cells. Thus, non-toxic curcumin, which targets p300/CBP, may serve as a lead compound in combinatorial HIV therapeutics.
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            Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects

            Turmeric is a curry spice that originated from India, which has attracted great interest in recent decades because it contains bioactive curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione), a lipophilic polyphenol may work as an anticancer, antibiotic, anti-inflammatory, and anti-aging agent as suggested by several in vitro, in vivo studies and clinical trials. However, poor aqueous solubility, bioavailability, and pharmacokinetic profiles limit curcumin’s therapeutic usage. To address these issues, several curcumin formulations have been developed. However, suboptimal sample preparation and analysis methodologies often hamper the accurate evaluation of bioactivities and their clinical efficacy. This review summarizes recent research on biological, pharmaceutical, and analytical aspects of the curcumin. Various formulation techniques and corresponding clinical trials and in vivo outcomes are discussed. A detailed comparison of different sample preparation (ultrasonic, pressurized liquid extraction, microwave, reflux) and analytical (FT-IR, FT-NIR, FT-Raman, UV, NMR, HPTLC, HPLC, and LC-MS/MS) methodologies used for the extraction and quantification of curcuminoids in different matrices, is presented. Application of optimal sample preparation, chromatographic separation, and detection methodologies will significantly improve the assessment of different formulations and biological activities of curcuminoids.
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              Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.

              Histone acetylation plays critical roles in chromatin remodeling, DNA repair, and epigenetic regulation of gene expression, but the underlying mechanisms are unclear. Proteasomes usually catalyze ATP- and polyubiquitin-dependent proteolysis. Here, we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes ("spermatoproteasomes") contain a spermatid/sperm-specific α subunit α4 s/PSMA8 and/or the catalytic β subunits of immunoproteasomes in addition to PA200. Deletion of PA200 in mice abolishes acetylation-dependent degradation of somatic core histones during DNA double-strand breaks and delays core histone disappearance in elongated spermatids. Purified PA200 greatly promotes ATP-independent proteasomal degradation of the acetylated core histones, but not polyubiquitinated proteins. Furthermore, acetylation on histones is required for their binding to the bromodomain-like regions in PA200 and its yeast ortholog, Blm10. Thus, PA200/Blm10 specifically targets the core histones for acetylation-mediated degradation by proteasomes, providing mechanisms by which acetylation regulates histone degradation, DNA repair, and spermatogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                IJN
                intjnano
                International Journal of Nanomedicine
                Dove
                1176-9114
                1178-2013
                17 March 2020
                2020
                : 15
                : 1853-1862
                Affiliations
                [1 ]Shanghai Key Laboratory of Reproductive Medicine, Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine , Shanghai 200025, People’s Republic of China
                [2 ]Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011, People’s Republic of China
                Author notes
                Correspondence: Qiang Liu Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine , 280 South Chongqing Road, Shanghai200025, People’s Republic of ChinaTel +86 21 63846590 Ext. 776761 Email qliu0122@shsmu.edu.cn
                [*]

                These authors contributed equally to this work

                Article
                237254
                10.2147/IJN.S237254
                7086405
                32256064
                c7ad1f3d-8495-4efc-a047-091b62b0b714
                © 2020 Xia et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 07 November 2019
                : 14 February 2020
                Page count
                Figures: 7, References: 44, Pages: 10
                Categories
                Original Research

                Molecular medicine
                nano-curcumin,reproductive toxicity,sertoli cell,sperm motility,spermatogenesis
                Molecular medicine
                nano-curcumin, reproductive toxicity, sertoli cell, sperm motility, spermatogenesis

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