Home α-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice
Article
Licensed
Unlicensed Requires Authentication

α-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice

ALA attenuates nicotine-induced transplacental toxicity
  • Santo K. Anto , Naresh Koyada , Sabbir Khan and Gopabandhu Jena EMAIL logo
Published/Copyright: September 22, 2016
Journal of Basic and Clinical Physiology and Pharmacology
From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 27 Issue 6

Abstract

Background:

Smoking during pregnancy is associated with numerous fetal and developmental complications and reproductive dysfunctions in the offspring. Nicotine is one of the key chemicals of tobacco responsible for addiction. The present study was aimed to investigate the protective role of α-lipoic acid (ALA) during the transplacental nicotine-induced germ cell and DNA damage in the offspring of Swiss mice.

Methods:

Pregnant mice were treated with nicotine (20 mg/kg/day) in drinking water from 10 to 20 days of gestation period, and ALA (120 mg/kg/day) was administered orally for the same period. Endpoint of evaluation includes general observations at delivery and throughout the study, litter weight and size, sperm count and sperm head morphology, while structural damages and protein expression were assessed by histology and immunohistochemistry, respectively.

Results:

Maternal nicotine exposure led to decreased growth rate, litter and testicular weight, testosterone level, 3β-HSD expression and sperm count as well as increased sperm head abnormalities, micronucleus frequency and 8-oxo-dG positive cells, and the effects have been restored by ALA supplementation.

Conclusions:

The present study clearly demonstrated that ALA ameliorates nicotine-associated oxidative stress, DNA damage and testicular toxicity in the offspring by improving steroidogenesis, spermatogenesis and sperm count.

Keywords: α-lipoic acid; DNA damage; germ cell; mice; nicotine; trans-placental exposure
Corresponding author: Dr. Gopabandhu Jena, MPhil, PhD, Associate Professor, Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062, India, Phone: +91-172-2214683 (Extn. 2152), Fax: +91-172-2214692, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire contents of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by the National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Punjab-160062, India.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Kapoor D, Jones T. Smoking and hormones in health and endocrine disorders. Eur J Endocrinol 2005;152:491–9.10.1530/eje.1.01867Search in Google Scholar

2. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Mathews T, Kirmeyer S, et al. Births: final data for 2007. Natl Vital Stat Rep 2010;58:1–125.Search in Google Scholar

3. Talhout R, Schulz T, Florek E, Van Benthem J, Wester P, Opperhuizen A. Hazardous compounds in tobacco smoke. Int J Environ Res Public Health 2011;8:613–28.10.3390/ijerph8020613Search in Google Scholar

4. Brčić Karačonji I. Facts about nicotine toxicity. Arh Hig Rad Toksikol 2005;56:363–71.Search in Google Scholar

5. Kallala R, Barrow J, Graham SM, Kanakaris N, Giannoudis PV. The in vitro and in vivo effects of nicotine on bone, bone cells and fracture repair. Expert Opin Drug Saf 2013;12:209–33.10.1517/14740338.2013.770471Search in Google Scholar

6. Patterson F, Benowitz N, Shields P, Kaufmann V, Jepson C, Wileyto P, et al. Individual differences in nicotine intake per cigarette. Cancer Epidemiol Biomark Prev 2003;12: 468–71.Search in Google Scholar

7. Russell M, Feyerabend C, Cole P. Plasma nicotine levels after cigarette smoking and chewing nicotine gum. Br Med J 1976;1:1043–6.10.1136/bmj.1.6017.1043Search in Google Scholar

8. Cnattingius S. The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine Tob Res 2004;6:S125–40.10.1080/14622200410001669187Search in Google Scholar

9. Mortensen JT, Thulstrup AM, Larsen H, Møller M, Sørensen HT. Smoking, sex of the offspring, and risk of placental abruption, placenta previa, and preeclampsia: a population-based cohort study. Acta Obstet Gynecol Scand 2001;80:894–8.10.1080/791200704Search in Google Scholar

10. Lundgren EM, Cnattingius S, Jonsson B, Tuvemo T. Intellectual and psychological performance in males born small for gestational age with and without catch-up growth. Pediatr Res 2001;50:91–6.10.1203/00006450-200107000-00017Search in Google Scholar

11. Birnbaum SC, Kien N, Martucci RW, Gelzleichter TR, Witschi H, Hendrickx AG, et al. Nicotine-or epinephrine-induced uteroplacental vasoconstriction and fetal growth in the rat. Toxicology 1994;94:69–80.10.1016/0300-483X(94)90029-9Search in Google Scholar

12. Storgaard L, Bonde JP, Ernst E, Spanô M, Andersen CY, Frydenberg M, et al. Does smoking during pregnancy affect sons’ sperm counts? Epidemiology 2003;14:278–86.10.1097/01.EDE.0000059922.73864.3ESearch in Google Scholar

13. Jensen MS, Mabeck LM, Toft G, Thulstrup AM, Bonde JP. Lower sperm counts following prenatal tobacco exposure. Hum Reprod 2005;20:2559–66.10.1093/humrep/dei110Search in Google Scholar PubMed

14. Ramlau-Hansen CH, Thulstrup AM, Storgaard L, Toft G, Olsen J, Bonde JP. Is prenatal exposure to tobacco smoking a cause of poor semen quality? A follow-up study. Am J Epidemiol 2007;165:1372–9.10.1093/aje/kwm032Search in Google Scholar

15. Segarra AC, Strand FL. Perinatal administration of nicotine alters subsequent sexual behavior and testosterone levels of male rats. Brain Res 1989;480:151–9.10.1016/0006-8993(89)91577-1Search in Google Scholar

16. Jensen TK, Henriksen TB, Hjollund NH, Scheike T, Kolstad H, Giwercman A, et al. Adult and prenatal exposures to tobacco smoke as risk indicators of fertility among 430 Danish couples. Am J Epidemiol 1998;148:992–7.10.1093/oxfordjournals.aje.a009576Search in Google Scholar

17. Bruin JE, Petre MA, Lehman MA, Raha S, Gerstein HC, Morrison KM, et al. Maternal nicotine exposure increases oxidative stress in the offspring. Free Radic Biol Med 2008;44:1919–25.10.1016/j.freeradbiomed.2008.02.010Search in Google Scholar

18. Buettner GR. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys 1993;300:535–43.10.1006/abbi.1993.1074Search in Google Scholar

19. Halliwell B. How to characterize a biological antioxidant. Free Radic Res Commun 1990;9:1–32.10.3109/10715769009148569Search in Google Scholar

20. Cocuzza M, Sikka SC, Athayde KS, Agarwal A. Clinical relevance of oxidative stress and sperm chromatin damage in male infertility: an evidence based analysis. Int Braz J Urol 2007;33:603–21.10.1590/S1677-55382007000500002Search in Google Scholar

21. Budin SB, Othman F, Louis S, Bakar MA, Radzi M, Osman K, et al. Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats. Rom J Morphol Embryol 2009;50:23–30.Search in Google Scholar

22. Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant α-lipoic acid. Free Radic Biol Med 1997;22:359–78.10.1016/S0891-5849(96)00269-9Search in Google Scholar

23. Roy S, Sen CK, Tritschler HJ, Packer L. Modulation of cellular reducing equivalent homeostasis by α-lipoic acid: mechanisms and implications for diabetes and ischemic injury. Biochem Pharmacol 1997;53:393–9.10.1016/S0006-2952(96)00764-2Search in Google Scholar

24. Othman AI, El-Missiry MA, Koriem KM, El-Sayed AA. Alfa-lipoic acid protects testosterone secretion pathway and sperm quality against 4-tert-octylphenol induced reproductive toxicity. Ecotoxicol Environ Saf 2012;81:76–83.10.1016/j.ecoenv.2012.04.018Search in Google Scholar PubMed

25. Jensen TK, Jorgensen N, Punab M, Haugen TB, Suominen J, Zilaitiene B, et al. Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries. Am J Epidemiol 2004;159:49–58.10.1093/aje/kwh002Search in Google Scholar

26. Oyeyipo IP, Raji Y, Emikpe BO, Bolarinwa AF. Effects of nicotine on sperm characteristics and fertility profile in adult male rats: a possible role of cessation. J Reprod Infertil 2011;12:201–7.Search in Google Scholar

27. Khan S, Jena GB. Effect of sodium valproate on the toxicity of cyclophosphamide in the testes of mice: influence of pre- and post-treatment schedule. Toxicol Int 2013;20:68–76.10.4103/0971-6580.111562Search in Google Scholar

28. Khan S, Ahmad T, Parekh CV, Trivedi PP, Kushwaha S, Jena G. Investigation on sodium valproate induced germ cell damage, oxidative stress and genotoxicity in male Swiss mice. Reprod Toxicol 2011;32:385–94.10.1016/j.reprotox.2011.09.007Search in Google Scholar

29. Khan S, Jena G. Sodium butyrate, a HDAC inhibitor ameliorates eNOS, iNOS and TGF-beta1-induced fibrogenesis, apoptosis and DNA damage in the kidney of juvenile diabetic rats. Food Chem Toxicol 2014;73:127–39.10.1016/j.fct.2014.08.010Search in Google Scholar

30. Namoju RC, Khan S, Patel RS, Shera FY, Trivedi PP, Kushwaha S, et al. Pre-pubertal exposure of cytarabine-induced testicular atrophy, impaired spermatogenesis and germ cell DNA damage in SD rats. Toxicol Mech Methods 2014;24:703–12.10.3109/15376516.2014.970679Search in Google Scholar

31. Khan S, Jena G, Tikoo K, Kumar V. Valproate attenuates the proteinuria, podocyte and renal injury by facilitating autophagy and inactivation of NF-κB/iNOS signaling in diabetic rat. Biochimie 2015;110:1–16.10.1016/j.biochi.2014.12.015Search in Google Scholar

32. Ahmad T, Shekh K, Khan S, Vikram A, Yadav L, Parekh CV, et al. Pretreatment with valproic acid, a histone deacetylase inhibitor, enhances the sensitivity of the peripheral blood micronucleus assay in rodents. Mutat Res 2013;751:19–26.10.1016/j.mrgentox.2012.10.009Search in Google Scholar

33. Dahlström A, Lundell B, Curvall M, Thapper L. Nicotine and cotinine concentrations in the nursing mother and her infant. Acta Paediatr 1990;79:142–7.10.1111/j.1651-2227.1990.tb11430.xSearch in Google Scholar

34. Luck W, Nau H. Nicotine and cotinine concentrations in serum and urine of infants exposed via passive smoking or milk from smoking mothers. J Pediatr 1985;107:816–20.10.1016/S0022-3476(85)80427-3Search in Google Scholar

35. Wickström R. Effects of nicotine during pregnancy: human and experimental evidence. Curr Neuropharm 2007;5:213.10.2174/157015907781695955Search in Google Scholar PubMed PubMed Central

36. Mak V, Jarvi K, Buckspan M, Freeman M, Hechter S, Zini A. Smoking is associated with the retention of cytoplasm by human spermatozoa. Urology 2000;56:463–6.10.1016/S0090-4295(00)00700-7Search in Google Scholar

37. Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE, et al. Endocrine regulation of male fertility by the skeleton. Cell 2011;144:796–809.10.1016/j.cell.2011.02.004Search in Google Scholar PubMed PubMed Central

38. Guntur AR, Rosen CJ. Bone as an endocrine organ. Endocr Pract 2012;18:758–62.10.4158/EP12141.RASearch in Google Scholar PubMed PubMed Central

39. Hermizi H, Faizah O, Ima-Nirwana S, Ahmad Nazrun S, Luke D, Norazlina M. Nicotine impaired bone histomorphometric parameters and bone remodeling biomarkers in Sprague–Dawley male rats. Ann Microsc 2007;7:10–24.Search in Google Scholar

40. Sun F, Ko E, Martin RH. Is there a relationship between sperm chromosome abnormalities and sperm morphology? Reprod Biol Endocrinol 2006;4:1.10.1186/1477-7827-4-1Search in Google Scholar PubMed PubMed Central

41. Miranda-Spooner M, Paccola CC, Neves FM, de Oliva SU, Miraglia SM. Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation. Andrology 2016;4:218–31.10.1111/andr.12100Search in Google Scholar PubMed

42. Jana K, Samanta PK, De DK. Nicotine diminishes testicular gametogenesis, steroidogenesis, and steroidogenic acute regulatory protein expression in adult albino rats: possible influence on pituitary gonadotropins and alteration of testicular antioxidant status. Toxicol Sci 2010;116:647–59.10.1093/toxsci/kfq149Search in Google Scholar PubMed

43. Jana K, Dutta A, Chakraborty P, Manna I, Firdaus SB, Bandyopadhyay D, et al. Alpha-lipoic acid and n-acetylcysteine protects intensive swimming exercise-mediated germ-cell depletion, pro-oxidant generation, and alteration of steroidogenesis in rat testis. Mol Reprod Dev 2014;81:833–50.10.1002/mrd.22354Search in Google Scholar PubMed

44. Ozbal S, Ergur BU, Erbil G, Tekmen I, Bagriyanik A, Cavdar Z. The effects of alpha-lipoic acid against testicular ischemia-reperfusion injury in rats. Sci World J 2012;2012:489248.10.1100/2012/489248Search in Google Scholar PubMed PubMed Central

45. Yeni D, Fidan AF, Cigerci IH, Konuk M, Avdatek F, Gundogan M. Effect of alpha-lipoic acid on sperm quality, reproductive tract measures in thinner exposed rats. Andrologia 2012;44(1 Suppl):74–80.10.1111/j.1439-0272.2010.01140.xSearch in Google Scholar PubMed

46. Nakano T, Masuda M, Suzuki T, Ohshima H. Inhibition by polyphenolic phytochemicals and sulfurous compounds of the formation of 8-chloroguanosine mediated by hypochlorous acid, human myeloperoxidase, and activated human neutrophils. Biosci Biotechnol Biochem 2012;76:2208–13.10.1271/bbb.120482Search in Google Scholar PubMed

47. Kleinsasser NH, Sassen AW, Semmler MP, Harréus UA, Licht A-K, Richter E. The tobacco alkaloid nicotine demonstrates genotoxicity in human tonsillar tissue and lymphocytes. Toxicol Sci 2005;86:309–17.10.1093/toxsci/kfi186Search in Google Scholar PubMed

48. Ogura R, Ikeda N, Yuki K, Morita O, Saigo K, Blackstock C, et al. Genotoxicity studies on green tea catechin. Food Chem Toxicol 2008;46:2190–200.10.1016/j.fct.2008.02.016Search in Google Scholar PubMed

Supplemental Material:

The online version of this article (DOI: 10.1515/jbcpp-2015-0151) offers supplementary material, available to authorized users.

Received: 2015-12-5
Accepted: 2016-6-7
Published Online: 2016-9-22
Published in Print: 2016-11-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Behavior and Neuroprotection
  3. Analgesic properties of aqueous leaf extract of Haematostaphis barteri: involvement of ATP-sensitive potassium channels, adrenergic, opioidergic, muscarinic, adenosinergic and serotoninergic pathways
  4. Correlative study of peripheral ATP1A1 gene expression level to anxiety severity score on major depressive disorder patients
  5. Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice
  6. Reproduction
  7. Tobacco smoke exposure induces irreversible alteration of testicular function in prepubertal rats
  8. Oxidative Stress
  9. α-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice
  10. Effects of nicotine in the presence and absence of vitamin E on morphology, viability and osteogenic gene expression in MG-63 osteoblast-like cells
  11. Metabolism
  12. Age-dependent features of CYP3A, CYP2C, and CYP2E1 functioning at metabolic syndrome
  13. Exercise increases the level of plasma orexin A in humans
  14. Inflammation
  15. Drug combinations in diabetic neuropathic pain: an experimental validation
  16. Pharmacokinetics of ceftriaxone in patients undergoing continuous renal replacement therapy
  17. Hematology
  18. Phenotypic homogeneity with minor deviance in osmotic fragility of Sahel goat erythrocytes in non-ionic sucrose media during various physiologic states
  19. Protection against arsenic-induced hematological and hepatic anomalies by supplementation of vitamin C and vitamin E in adult male rats
  20. One more health benefit of blood donation: reduces acute-phase reactants, oxidants and increases antioxidant capacity
  21. Phytotherapy
  22. Antithrombotic and cytotoxic activities of four Bangladeshi plants and PASS prediction of their isolated compounds
https://doi.org/10.1515/jbcpp-2015-0151
Keywords for this article
α-lipoic acid; DNA damage; germ cell; mice; nicotine; trans-placental exposure

Articles in the same Issue

  1. Frontmatter
  2. Behavior and Neuroprotection
  3. Analgesic properties of aqueous leaf extract of Haematostaphis barteri: involvement of ATP-sensitive potassium channels, adrenergic, opioidergic, muscarinic, adenosinergic and serotoninergic pathways
  4. Correlative study of peripheral ATP1A1 gene expression level to anxiety severity score on major depressive disorder patients
  5. Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice
  6. Reproduction
  7. Tobacco smoke exposure induces irreversible alteration of testicular function in prepubertal rats
  8. Oxidative Stress
  9. α-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice
  10. Effects of nicotine in the presence and absence of vitamin E on morphology, viability and osteogenic gene expression in MG-63 osteoblast-like cells
  11. Metabolism
  12. Age-dependent features of CYP3A, CYP2C, and CYP2E1 functioning at metabolic syndrome
  13. Exercise increases the level of plasma orexin A in humans
  14. Inflammation
  15. Drug combinations in diabetic neuropathic pain: an experimental validation
  16. Pharmacokinetics of ceftriaxone in patients undergoing continuous renal replacement therapy
  17. Hematology
  18. Phenotypic homogeneity with minor deviance in osmotic fragility of Sahel goat erythrocytes in non-ionic sucrose media during various physiologic states
  19. Protection against arsenic-induced hematological and hepatic anomalies by supplementation of vitamin C and vitamin E in adult male rats
  20. One more health benefit of blood donation: reduces acute-phase reactants, oxidants and increases antioxidant capacity
  21. Phytotherapy
  22. Antithrombotic and cytotoxic activities of four Bangladeshi plants and PASS prediction of their isolated compounds
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 26.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jbcpp-2015-0151/html
Scroll to top button