At the same time, the purpose of this study was to evaluate the reaction of the reproductive system on the carbon nanostructured material "Taunit (multi-walled carbon nanotubes), that was injected to laboratory miceyesBelgorod State Universit

Gusev, A. A.

Polyakova, I. A.

Snegin, E. A.

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Reproductive toxicity of carbon nanostructured material - a promising carrier of drugs inlaboratory miceThis article has been downloaded from IOPscience. Please scroll down to see the full text article.2011 J. Phys.: Conf. Ser. 291 012052(http://iopscience.iop.org/1742-6596/291/1/012052)Download details:IP Address: 79.140.73.67The article was downloaded on 18/10/2011 at 08:22Please note that terms and conditions apply.View the table of contents for this issue, or go to the journal homepage for moreHome Search Collections Journals About Contact us My IOPscienceReproductive toxicity of carbon nanostructured material - a promising carrier of drugs in laboratory miceA.A. Gusev1, E.A. Snegin2, I.A. Polyakova1, E.B. Gorsheneva1, A.G. Tkachev3, A.V. Emeliyanov1, S.V. Shutova1, O.N. Zayceva1, A.V. Shuklinov1, A.V. Fedorov4, T.V. Vasilieva4, E.A. Smirnova4, E.M. Lazareva4,G.E. Onishenko41Tambov State University of the name of G.R. Derzhavin, 392000, Russia, Tambov, Internacionalnaya str., 33, e-mail: nanosecurity@mail.ru2Belgorod State University, 308015, Russia, Belgorod, Pobedy str., 853Tambov State Technical University, 392000, Russia, Tambov, str. Sovietskaya, 1064Moscow State University of the name of M.V. Lomonosov, Biological faculty, 119991, Russia, Moscow, Leninskie gory, 1/12, MSUINTRODUCTIONCurrently, to the prospects of nanotechnology is given an increasing worldwide attention. However, nanomaterials  might have very different physical and chemical properties and biological (including toxic) effect than substance in the usual physical and chemical condition that is why  they  are refered to new types of materials and products. Among the actual and potential areas of their application - microelectronics, micromechanics,  energy,  environment,  agriculture,  etc.  Especially  we  focus  on medical applications – such as carbon nanotubes, due to its unique properties which is a high strength, hydrophobicity, chemical inertness, high penetrating power, are ideal  carriers  for  drug  delivery,  providing  targeted,  the  preservation  of  the  active components in the internal environment of an organism , prolongation of action [1]. In a short while a close contact of humans and other biological objects are expected and this problem is one of the most considered issues of the science nowadays. At the same time, the question of the toxicity of carbon nanotubes is the subject of ongoing debate [2].  There are number of papers  which  demonstrate the  negative impact of these structures on  living organisms [3,4,5].  More over,  the issues of reproductive toxicity of carbon nanotubes are studied improperly. At the same time, the purpose of this  study was to  evaluate  the  reaction of  the  reproductive  system on the carbon nanostructured material "Taunit (multi-walled carbon nanotubes), that was injected to laboratory mice. Nutritional path was selected as a way of injection as it is the most III Nanotechnology International Forum IOP PublishingJournal of Physics: Conference Series 291 (2011) 012052 doi:10.1088/1742-6596/291/1/012052Published under licence by IOP Publishing Ltd 1possible method of proceeding nanomaterials into a body [6]. OBJECTS AND METHODS The object of  research - a carbon nanomaterial "Taunit" (multiwalled carbon nanotubes),  which  is  produced  on  an  industrial  scale  LLC  NanoTechCenter (Tambov).  This  material  is  one-dimensional,  nanoscale,  filamentous  formation  of polycrystalline graphite, a cylindrical shape with an internal channel in the form of loose  powder  black.  Hydrophobic,  chemically  inert,  purity  -  more  than  98%. Granules  of nanomaterial of  micrometric   dimensions have a structure of  a tangled bundles  of  multiwalled  tubes  (Fig.  1),  method  of  obtaining  -  chemical  vapor deposition on a metal catalyst or CVD-process. "Taunit” is a promising material for the  aerospace  Industry,  nuclear,  space  technology,  medicine,  pharmaceutics, production of supercomputers, video equipment, flat screen monitors, filters, multi-purpose.  Addition  of  "Taunit"  improves  the  quality  of  lubricants,  structural composites  and  building  materials.  Granules  "Taunita"  can  serve  as  carriers  of catalysts or drugs, as well as adsorbents, cold electron emission sources [7]. Fig. 1. Electron micrographs of nanostructured carbon material "Taunit". Photos courtesy LLC “NanoTechCenter", TambovThe experiment consisted of two parts: the first assessed the physiological effect of the investigated nanomaterials in males, in the second - on female laboratory mice.1. To study the effects of nanomaterials on male reproductive function formed by two coeval group of animals (experimental and control groups) consisting of 10 III Nanotechnology International Forum IOP PublishingJournal of Physics: Conference Series 291 (2011) 012052 doi:10.1088/1742-6596/291/1/0120522adult male non-linear laboratory mice each. Throughout the experiment, all animals were kept in standard conditions. Quarantined for 10 days. Within 30 days of the experimental group was administered orally  by UNM "Taunit" by replacing the drinking water in colloidal aqueous solution. The solution was prepared in distilled water using ultrasonic installation. The sample initial CNM prepared for TEM as follows. 25 mg of nanomaterial placed on a surface of liquid pitch  (Epon  812),  poured  in  a  test  tube,  centrifuged  3  min  at  6000  ×g  and polymerized  by  a  standard  technique.   Ultrathin  cuts  filled  in  Epon  investigated samples methods TEM and diffractions of electrons by means of appearing through electronic microscopes JEM-1011 (JEOL) with digital camera GATAN ES500W and LEO 912АВ (Carl Zeiss).The average daily dose of the material for each male in the experimental group was 30 mg / kg. Assess the overall condition of the animals.The control  group consisted of mice injected with distilled water in similar quantities.Upon expiration  of  the exposure to  each male  were sat down to 3 Virginy unexposed females. Noted the presence of sexual behavior. Replanting of females to male  guinea  was  performed  weekly  for  three  weeks.  Separated females  were dissected  after  15-17  days.  Estimated  number  of  pregnant  females,  females  with living fetus, with a dead fetus, the number of living and dead fetuses per litter.2. To assess the actions of nanomaterial on the reproductive function of females formed two coeval group of animals (experimental and control groups) consisting of 10 adult  females, non-linear laboratory mice each. Throughout the experiment,  all animals  were  kept  in  standard  conditions.  Quarantined  for  10  days.  Colloidal aqueous solution of nanomaterials for watering animals prepared as above. After several days of sharing content with the mature unexposed males, females were separated by individual cells and from that moment passed by watering test fluid. The experiment  was  completed  after  the  end  of  the  nursing  offspring.  Assessed the following indicators:% of female deaths (overall and for each day of the experiment),% mortality of young during the first three days of life;% not given birth III Nanotechnology International Forum IOP PublishingJournal of Physics: Conference Series 291 (2011) 012052 doi:10.1088/1742-6596/291/1/0120523to females, the number of dead embryos in females, fertility, and general condition of the females.At each stage, in addition to the experimental group, and contained a similarly studied control group of mice, which is used for drinking distilled water. RESULTS AND DISCUSSION1. Preliminary  by  us  it  has  been  spent  characterization  of  structure  of nanomaterial. On images structure of CNM (fig. 2А) - conglomerates of MWCNT is visible.  Morphological features MWCNT are well  visible in drawing 2B. The site with MWCNT, not containing graphitized carbon (fig. 2C), has been characterised by the method of electrons diffraction. As is shown in fig. 2D, MWCNT thanks to the ordered  periodic  packing  of  atoms  of  carbon  form  on  electronogram  rings, characteristic for polycrystalline samples.Fig. 2. The structural characteristic of nanomaterial. Explanatories in the text A C B D III Nanotechnology International Forum IOP PublishingJournal of Physics: Conference Series 291 (2011) 012052 doi:10.1088/1742-6596/291/1/01205242.According to the method of study to males from the experimental and control groups during the 3 weeks of sit down Virginy unexposed females of reproductive age.  In both groups,  there were the presence of normal sexual  behavior.  External lesions in the experimental group was noted. Follow-up for females revealed that the carbon  nanomaterial,  introduced  orally  in  a  dosage  study,  causes  complete  male sterility in laboratory mice (Fig. 3). ExperimentControl051015202530Week 1Week 2Week 33.Fig.  3.  The  number  of  successfully  inseminated  females  during  the  experimentStudy  of  histological  sections  of  testes  of  experimental  animals  showed significant  structural  damage  in  comparison  with  the  control  group (Fig.  4).  The result can indicate that, along with bodies such as the liver, spleen and lungs testes are target organs for the nanoparticles. Fig. 4. Histological sections of testes of mice from the control (A) and experimental (B) groups.  The right  image shows disturbance seminiferous  tubules,  numerous necrotic  cells.  The III Nanotechnology International Forum IOP PublishingJournal of Physics: Conference Series 291 (2011) 012052 doi:10.1088/1742-6596/291/1/0120525photos were made members of the Biological Faculty of Moscow State University. MV Lomonosov Moscow State University under the guidance of professor of cell biology and histology, Dr. G. OnishchenkoA possible  mechanism of  toxicity  of  carbon  nanotubes  is  oxidative  stress. Carbon nanotubes are cylindrical in shape. Presence in the tissue long enough and hard (Multilayer) of nanotubes causes a "failure" in the behavior of macrophages [8]. These  cells  are  unable  to  swallow  "such  a  large  particle,  and  only  emit  toxic environment  oxygen  species  (ROS)  and  hydrolytic  enzymes,  causing  an inflammatory  reaction  [8].  Oxidative  stress  can  cause  infertility  in  males. Hyperproduction of reactive oxygen species leads to a decrease in cell viability in semen  that  leads  to  an  inability  to  fertilize  [9].In the course of nanomaterial toxicity may cause chromosomal aberrations. Most of them occur  in  the  chromosomes derived from the father  [10].  Perhaps it  is  these violations occurred during the experiment, which ultimately led to reduced viability or  sperm,  or  cause  damage to  spermatogenic  tissue,  which  prevented  the  normal formation of germ cells. As a result, males of both experimental groups could lose the ability to fertilize.Stress resulting from mechanical injury or poisoning of nanomaterials may be accompanied  by  increased  levels  of  stress  hormones  -  corticosteroids  and catecholamines. Hormonal changes that accompany stress can cause pathological or adaptive changes at the level of the CNS, particularly in the hypothalamus, resulting in  possible  violation  of  the  secretion  of  the  hormone GnRH in  it,  it  reduces  the release of luteinizing hormone, acting in the testis are Leydig cells, which in response secrete the hormone testosterone. This may subsequently cause dysfunction of the reproductive  system  [11].  Thus,  hormonal  imbalance  under  the  influence  of nanomaterials  could  lead  to  suppression  of  reproductive  function  at  the  level  of humoral regulation of spermatogenesis.2. To study the effect of nanomaterials on female reproductive function, after the joint maintenance of a mature unexposed males and females during pregnancy III Nanotechnology International Forum IOP PublishingJournal of Physics: Conference Series 291 (2011) 012052 doi:10.1088/1742-6596/291/1/0120526and nursing were treated with test fluid. Pathological abnormalities in the appearance and behavior of experimental females have been recorded, on the contrary, they are more  heavily  recruited  body  weight  than  females  of  the  control  group.  The  positive  trend  was  observed  in  the  analysis  of  the  studied  indicators  of reproductive activity. It was found that when exposed to the organism UNM "Town, administered orally in a dosage of the study is an increase in female fertility by 30% reduction in mortality of young animals by 46% and a decrease in the proportion of individuals not given birth by 17% (Fig. 5).0510152025303540Fruitfulness of females % of  destruction of young growth % of not given birth femalesControl ExperimentFig. 5. Comparison srednegruppovyh indicators of female fertility, the proportion who died young, none gave birth to female mice in the control and experimental groups. A similar effect can be explained as follows. Different reactions to the same effect in the first and second experiments, possibly connected with the peculiarities of physiology of male and female organisms, which are expressed in dissimilar norms of reaction,  specific  to  each gender  [12].  For  example,  the  above-described possible hormonal imbalance in the male body can cause spermatoksichesky effect, while in the  female  body  similar  hormonal  pattern  may  stimulate  the  activity  of  the reproductive  system.  Anyway,  the  mechanisms  of  observed  changes  we  require deeper investigation.III Nanotechnology International Forum IOP PublishingJournal of Physics: Conference Series 291 (2011) 012052 doi:10.1088/1742-6596/291/1/0120527CONCLUSIONS Thus,  study  the  effect  of  industrial  carbon produced  by  the  nanostructured material  on  the  reproductive  function  of  laboratory  mice.  Shown  that  oral administration  of  colloidal  aqueous  solution of  carbon nanomaterial  "Taunit"  at  a dosage of 30 mg / kg of body weight is a cause of infertility in male mice. At the opening of potentially pregnant  females, none in the uterine horns, there were no signs of pregnancy, which constitutes a serious violation of the reproductive function of males under the influence of nanomaterials. At the same time, studied the dosage of  nanomaterial  stimulates  increase  fertility  in  females,  leads  to  a  reduction  in mortality of young animals, as well as a decrease in the proportion of individuals not given  birth.The results can be taken into account when developing content standards of carbon nanomaterials in the environment, contact with animals and humans, as well as the creation based on multiwalled carbon nanotubes, next-generation drugs.REFERENCES 1. Foster L. Nanotechnologies. A science, innovations, possibilities.  Moscow: Technosfera, 2008. – 352 p.2.  Zhao  Yuliang,  Xing  Genmei,  Chai  Zhifang.  Are  carbon  nanotubes  safe?  //  Nature Nanotechnology. №4, March 2008. P. 191-192.3. Kostarelos  K.  The  long  and  short  of  carbon  nanotube  toxicity  //  Nature Biotechnology, №7, July 2008. V. 26. P. 774-776.4. Miyawaki  J.,  Yudasaka  M.,  Azami  T.  et  al.  Toxicity  of  Single-Walled  Carbon Nanohorns // Acsnano, №2, 2008. V. 2. P. 213–226. 5. Poland C.  A.,  Duffin  R.,  Kinloch I.  et  al.  Carbon nanotubes  introduced into  the abdominal  cavity  of  mice  show  asbestoslike  pathogenicity  in  a  pilot  study  //  Nature Nanotechnology. July 2008. V. 3. P. 423-428.6. Onishenko G.G. The decision of the Main state health officer of the Russian Federation III Nanotechnology International Forum IOP PublishingJournal of Physics: Conference Series 291 (2011) 012052 doi:10.1088/1742-6596/291/1/0120528from October,  31st,  2007 №79 Moscow «About  the  statement  of  the  Concept  of  toxicological researches,  methodology  of  an  estimation  of  risk,  methods  of  identification  and  quantitative definition  nanomaterial»  [Electronic  resource].  URL: http://www.rospotrebnadzor.ru/documents/postanov/1344/ (Reference date: 12.02.2010).7.  Tkachev  A.G.,  Zolotuhin  I.V.  Equipment  and  methods  of  synthesis  solid-state nanostructure: the monography / – М.: " Publishing Mashinostroenie-1", 2007. – 316 p.8. Nasibullaev S.K.  Fulleren their derivatives and  nanotubes [Electronic resource]. URL: http://originweb.info/education/chemistry/fullerenes6.html (Reference date: 22.02.2010).9.  Bikova M.V.  Redoks-balance infringement  spermatozoids and seed plasma of  men at patospermii.  The  dissertation  author's  abstract  on  competition  of  a  scientific  degree  of Cand.Biol.Sci. Krasnoyarsk, 2008.10. Uiba V.V. Working out Medico - biological safety in the field of nanotechnologies [Elec-tronic  resource].  URL:  http://rusnanotech08.rusnanoforum.ru/sadm_files/disk/Docs/1/7/14.pdf (Reference date: 10.03.2010).11. Kettal V.M, Arki R.U. Pathology of endocrine system. The lane with English - SPb. - М: «The  Neva  dialect»  -  «Publishing  house  BINOM»,  2001.  -  336  p.,  ill.12.  Geodakyan  V.A. Differential death rate and norm of reaction man's and female. Jornal of the general biology. 35 № 3, 1974. P. 376—385.Research  is  executed  at  partial  support  of  the  state  contracts  №  16 24.09.2010 and № P 208  23.04.2010III Nanotechnology International Forum IOP PublishingJournal of Physics: Conference Series 291 (2011) 012052 doi:10.1088/1742-6596/291/1/0120529

Reproductive toxicity of carbon nanostructured material - a promising carrier of drugs in laboratory mice

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Reproductive toxicity of carbon nanostructured material - a promising carrier of drugs in laboratory mice

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