DNA damage in placenta and embryos of rats exposed to peat smoke; antigenotoxic effects of afobazole

Cover Page
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract


Background. It was shown that prenatal exposure to peat smoke leads to disturbances of fetal and postnatal development in rats. Genotoxic mechanisms may be involved to these deleterious effects. The objective of the present study was to evaluate the DNA damage and its modification by known antimutagen afobazole in placenta and embryo of rats, exposed to peat smoke. Materials and methods. Pregnant rats were exposed to filtered air (control), to peat smoke or to peat smoke with receiving of afobazole (1 or 10 mg/kg, per os) for 44 min, daily during days 1 to 13 of gestation. At the day 13 four placenta and embryo samples from each rat were obtained for DNA damage analysis using the alkaline comet assay. Results. A significant, 4-5 folds increase in the DNA damage values (% DNA in tail) was found in placenta and embryos of rats exposed to peat smoke. Genotoxic effects were generally more pronounced in placenta. Exposure to peat smoke together with receiving of afobazole at the doses 1 and 10 mg/kg showed a significant, 53-60 % decrease in the mean % DNA in tail values in both placenta and embryos. Clear inter and intra-individual differences in genotoxic as well as in antigenotoxic effects were observed. For the some placenta or embryo samples were seen reducing of DNA damage to the control level. Conclusion. Exposure of pregnant rats to peat smoke causes DNA damage in placenta and embryos. This smoke-induced genotoxicity might be decreased or prevented by antimutagenic agents.

Full Text

Restricted Access

About the authors

Dinara M Gorbatova

Zakusov Institute of Pharmacology, Russian Academy of Sciences

Email: pharmacevt07@mail.ru
Researcher, Laboratory of Drug Toxicology, a group of reproductive toxicity

Aliy K Zhanataev

Zakusov Institute of Pharmacology, Russian Academy of Sciences

Email: pharmacol@yandex.ru
Leading Researcher, Ph.D, Laboratory of Pharmacology and mutagenesis

Helena P Nemova

Zakusov Institute of Pharmacology, Russian Academy of Sciences

Email: nemova_elena@mail.ru
senior researcher, PhD, Laboratory of Drug Toxicology, a group of reproductive toxicity

Andrey D Durnev

Zakusov Institute of Pharmacology, Russian Academy of Sciences

Email: food2003@yandex.ru
Corresponding Member. Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Laboratory of Pharmacology and mutagenesis; Laboratory of Drug Toxicology, a group of reproductive toxicity

References

  1. Добрых В.А., Захарычева Т.А. Дым лесных пожаров и здоровье // Дальневосточный государственный медицинский университет (Хабаровск). - 2009. - С. 201 [Dobrykh VA, Zakharycheva TA. Smoke from wildfires and health. Public Educational Institution of Higher Professional Training Dalnevostochny state medical university. 2009:201. (In Russ).]
  2. Горбатова Д.М., Литвинова С.А., Дурнев А.Д., и др. Протективное влияние афобазола на потомство крыс, подвергнутых действию торфяного дыма // Бюллетень экспериментальной биологии и медицины. - 2014. - Т. 158. - С. 614-619. [Gorbatova DM, Litvinov SA, Durnev AD, et al. Afobazole protects rats exposed to peat smoke in utero. Bulletin of experimental biology and medicine. 2014;158:614-619 (In Russ, Eng).]. doi: 10.1007/s10517-015-2830-z.
  3. Горбатова Д.М., Немова Е.П., Соломина А.С., и др. Пренатальные эффекты продуктов сгорания торфа и их коррекция афобазолом у потомства крыс // Бюллетень экспериментальной биологии и медицины. - 2014 - Т. 158. - С. 604-608. [Gorbatova DM, Nemov EP, Solomina AS, et al. Prenatal effects of peat combustion products and afobazole correction thereof in the rat progeny. Bulletin of experimental biology and medicine. 2014;158:604-608 (In Russ, Eng).]. doi: 10.1007/s10517-015-2829-5.
  4. Дурнев А.Д., Жанатаев А.К., Шредер О.В., и др. Генотоксические поражения и болезни // Молекулярная медицина. - 2013. - № 3. - С. 3-19. [Durnev AD, Zhanataev AK, Schröder OW, et al. Genotoxic events and diseases. Molecular medicine. 2013;(3):3-19 (In Russ).].
  5. Дурнев А.Д., Соломина А.С., Жанатаев А.К., и др. Влияние афобазола на генотоксические эффекты табачного дыма в плаценте и в тканях эмбрионов крыс // Бюллетень экспериментальной биологии и медицины. - 2010. - Т. 149. - С. 286-289. [Durnev AD, Solomina AS, Zhanataev AK, et al. Effect of afobazole on genotoxic effects of tobacco smoke in the placenta and embryonic tissues of rats. Bulletin of experimental biology and medicine. 2010; (149):286-289 (In Russ, Eng).]
  6. Дурнев А.Д., Меркулов В.А., Жанатаев А.К., и др. Методические рекомендации по оценке ДНК-повреждений методом щелочного гель-электрофореза отдельных клеток в фармакологических исследованиях: Руководство по проведению доклинических исследований лекарственных средств. - Часть первая. - М.: Гриф и К, 2012. - С. 115-128. [Durnev AD, Merkulov VA, Zhanataev AK, et al. Methodical recommendations for DNA damage evaluation in pharmacological studies using alkaline single-cell gel electrophoresis. Guidelines for pre-clinical drug studies. Part one. Moscow, 2012; 115-128 (In Russ).].
  7. Разумная Ф.Г., Камилов Ф.Х., Капулер О.М., и др. К фармакологии афобазола // Фундаментальные исследования. - 2014. - № 7. - С. 848-855. [Razumnaja FG, Kamilov FKh, Kapuler OM, et al. To the pharmacology of Afobazole. Basic researches. 2014;(7):848-855 (In Russ).].
  8. Незнамов Г.Г., Сюняков Т.С., Золотов Н.Н., и др. Терапевтическое влияние анксиолитиков феназепама и афобазола на содержание малонового диальдегида в плазме крови и психическое состояние больных с тревожными расстройствами // Психические расстройства в общей медицине. - 2014. - № 2. - С. 40-47. [Neznamov GG, Syunyakov TS, Zolotov NN, et al. Therapeutic influence of anksiolitik of a fenazepam and Afobazole on the content of low-new dialdehyde in plasma of blood and a mental condition of patients with disturbing frustration. Mental disorders in the general medicine. 2014;(2):40-47 (In Russ).].
  9. Al-Gubory KH, Fowler PA, Garrel C. The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. Int J Biochem Cell Biol. 2010;42:1634-1650. doi: 10.1016/j.biocel.2010.06.001.
  10. Bojakowska I, Sokołowska G. Polycyclic aromatic hydrocarbons in materials of burned peatlands. Polish J of Environmental Studies. 2003;12(4):401-408.
  11. Cornwall GA, Carter MW, Bradshaw WS. The relationship between prenatal lethality or fetal weight and intrauterine position in rats exposed to diethylstilbestrol, zeranol, 3,4,3’,4’-tetrachlorobiphenyl, or cadmium. Teratology. 1984;30(3):341-349. doi: 10.1002/tera.1420300306.
  12. Hougaard KS, Campagnolo L, Chavatte-Palmer P, et al. A perspective on the developmental toxicity of inhaled nanoparticles. Reprod Toxicol. 2015;56:118-140. doi: 10.1016/j.reprotox.2015.05.01.
  13. Kim Y, Tong H, Daniels M, et al. Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices. Particle and Fibre Toxicology. 2014;11:29. doi: 10.1186/1743-8977-11-29.
  14. Kimura C, Watanabe K, Iwasaki A, et al. The severity of hypoxic changes and oxidative DNA damage in the placenta of early-onset preeclamptic women and fetal growth restriction. J Matern Fetal Neonatal Med. 2013;26(5):491-496. doi: 10.3109/14767058.2012.733766.
  15. Liu JC, Pereira G, Uhl SA, et al. A systematic review of the physical health impacts from non-occupational exposure to wildfire smoke. Environ Res. 2015;136:120-132. doi: 10.1016/j.envres.2014.10.015.
  16. OECD Guidelines for the Testing of Chemicals, Section 4/ Test No. 489: In Vivo Mammalian Alkaline Comet Assay., 2014. doi: 10.1787/9789264224179-en.
  17. Perera FP, Tang D, Wang S, Vishnevetsky J, et al. Prenatal polycyclic aromatic hydrocarbon (PAH) exposure and child behavior at age 6-7 years. Environ Health Perspect. 2012;120(6):921-926.
  18. Møller P, Loft S. Statistical analysis of comet assay results. Front Genet. 2014,5:292. doi: 10.3389/fgene.2014.00292.
  19. Popovicheva O, Kistler M, Kireeva E, et al. Physicochemical characterization of smoke aerosol during large-scale wildfires: Extreme event of August 2010 in Moscow. Atmospheric Environment. 2014; 96:405-414. doi: 10.1016/j.atmosenv.2014.03.026.
  20. Tozuka Y, Watanabe N, Osawa M, et al. Transfer of polycyclic aromatic hydrocarbons to fetuses and breast milk of rats exposed to diesel exhaust. J Health Sci. 2004;50:497-502. doi: 10.1248/jhs.50.497.
  21. Ward WF, Aceto HJr, Karp CH. The effect of intrauterine position on the radiosensitivity of rat embryos. Teratology. 1977;16(2):181-186. doi: 10.1002/tera.1420160212.
  22. Woollam DH, Millen JW. Influence of uterine position on the response of the mouse embryo to anoxia. Nature. 1962;194:990-991. doi: 10.1038/194990a0.

Supplementary files

Supplementary Files Action
1.
Fig. 1. DNA comet images of head cells of embryo from rat exposed to peat smoke (a) and control rat (b)

Download (45KB) Indexing metadata
2.
Fig. 2. Individual values of DNA damage in placentas and embryos from rats exposed to peat smoke (a) and rat receiving upon peat smoke exposure the Afobazole at the doses 1 mg/kg (b) and 10 mg/kg (c). (1-4), (5-8) etc. – placenta/embryo pair samples from individual animal

Download (315KB) Indexing metadata
3.
Table. DNA damage and its modification by afobazole in placenta and embryos from rats exposed to peat smoke
Download (135KB) Indexing metadata

Statistics

Views

Abstract - 680

PDF (Russian) - 425

Cited-By


Article Metrics

Metrics Loading ...

PlumX

Dimensions


Copyright (c) 2016 Gorbatova D.M., Zhanataev A.K., Nemova H.P., Durnev A.D.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies