Kemik Gelişiminde Nikotine Karşı Folik Asitin Etkileri
Year 2024,
Volume: 8 Issue: 1, 48 - 55, 29.04.2024
Kadirhan Doğan
,
Mehtap Nisari
,
Ahmet Payas
,
Tolga Ertekin
,
Hatice Güler
,
Özge Al
Abstract
Amaç: Gebelikte maruz kalınan nikotin sadece anneye değil, fetal dokulara da doğrudan veya dolaylı olarak zarar verir. Bu çalışmadaki amaç gebelik döneminde kullanılan nikotine karşı verilen folik asitin fetusların kemik gelişimine olası etkilerinin araştırılmasıdır.
Araçlar ve Yöntem: 18 yetişkin dişi sıçan kontrol, düşük doz nikotin (DDN), yüksek doz nikotin (YDN), düşük doz nikotin + folik asit (DDN + FA), yüksek doz nikotin + folik asit (YDN + FA) ve folik asit (FA) gruplarına eşit olarak ayrıldı. 20 gün boyunca 1 ml/kg serum fizyolojik (SF) solüsyonu kontrol grubuna, 3 mg/kg nikotin DDN'ye, 6 mg/kg nikotin YDN'ye, 3 mg/kg nikotin ve 400 µg/kg FA DDN+FA’ya, 6 mg/kg nikotin ve 400 µg/kg FA YDN+FA’ya, 400 µg/kg FA FA grubuna uygulandı. Gebeliğin 20. gününde sezaryen ile alınan fetüslerın kemikleri ikili iskelet boyama tekniği ile boyandı. Boyanan ön ve arka ekstremite kemikleri stereomikroskop altında fotoğraflandı. Kemik uzunluğu, kemikleşme derecesi ve kemikleşme yüzdesi ölçüldü. İstatistiki veriler R programlama dili (v. 3.2.3) kullanılarak değerlendirildi.
Bulgular: Kemik gelişimi DDN ve YDN gruplarında anlamlı derecede düşük; DDN+FA ve YDN+FA gruplarında kontrol grubuna yakındı (p<0.05).
Sonuç: Gebelikte kullanılan nikotin fetüslerin kemik gelişimini azaltırken, FA bu etkiyi azaltarak kemikleşmeyi arttırabilir.
Project Number
TYL-2016-6497
References
- 1. Yılmaz H, Ertekin T, Atay E, et al. Antioxidant role of melatonin against nicotine’s teratogenic effects on embryonic bone development. Iran J Basic Med Sci. 2018;21(8):787-793.
- 2. Nisari M, Ulger H, Unur E, Karaca O, Ertekin T. Effect of interleukin 12 (IL-12) on embryonic development and yolk sac vascularisation. Bratisl Lek Listy. 2014;115(9):532-537.
- 3. Lugg ST, Scott A, Parekh D, Naidu B, Thickett DR. Cigarette smoke exposure and alveolar macrophages: mechanisms for lung disease. Thorax. 2022;77(1):94-101.
- 4. Callahan PM, Terry AV Jr, Peitsch MC, Hoeng J, Koshibu K. Differential effects of alkaloids on memory in rodents. Sci Rep. 2021;11(1):9843.
- 5. Yüce B, Tengiz Fİ. Effects of tobacco use during pregnancy on infant and child health. D J Med Sci. 2020;6(2):70-73.
- 6. Marinucci L, Bodo M, Balloni S, Locci P, Baroni T. Sub-toxic nicotine concentrations affect extracellular matrix and growth factor signaling gene expressions in human osteoblasts. J Cell Physiol. 2014;229(12):2038-2048.
- 7. Kirschneck C, Proff P, Maurer M, Reicheneder C, Römer P. Orthodontic forces add to nicotine-induced loss of periodontal bone: An in vivo and in vitro study. J Orofac Orthop. 2015;76(3):195-212.
- 8. Payas A, Ekinci Y, Gürbüz K, et al. Vitamin B12 reduces the negative effects of nicotine on fetal bone development in the rats. Jt Dis Relat Surg. 2022;33(1):216-224.
- 9. Manavi KR, Alston-Mills BP, Thompson MP. History of tobacco, vitamin D and women. Int J Vitam Nutr Res. 2020;90(5-6):389-394.
- 10. Shulpekova Y, Nechaev V, Kardasheva S, et al. The Concept of Folic Acid in Health and Disease. Molecules. 2021;26(12):3731.
- 11. Vajda FJE, O’Brien TJ, Graham JE, et al. Folic Acid dose, valproate and fetal malformations. Epilepsy&Behavior. 2021;114:107569.
- 12. Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-2611.
- 13. Booth M, Powell N, Corfield C, French JM. An automated technique for double staining of bone and cartilage in fetal mouse skeletal specimens using alizarin red S and Alcian blue. Biotech Histochem. 2022;97(3):222-227.
- 14. Dingerkus G, Uhler LD. Enzyme Clearing Of Alcian Blue Stained Whole Small Vertebrates For Demonstration Of Cartilage. Stain Technol. 1977;52(4):229-232.
- 15. Liao YJ, Tang PC, Chen LR, Yang JR. A protocol for differential staining of cartilages and ossified bones in fetal and adult mouse skeletons using alcian blue and alizarin red S. J Histotechnol. 2020;43(4):204-209.
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- 17. Oruç Ş. Ratlarda Hamilelik Döneminde Verilen Nikotinin, Neonatal Dönemde Molar Dişler Üzerindeki Etkileri, Master Thesis, Dicle Üniversitesi; 1996. https://tez.yok.gov.tr/UlusalTezMerkezi/tezDetay.jsp?id=91qsG18yUN59V_N5VMHDKw&no=91qsG18yUN59V_N5VMHDKw. Accessed 01 April, 2023.
- 18. Patel RA, Wilson RF, Patel PA, Palmer RM. The Effect of Smoking On Bone Healing. Bone Joint Res. 2013;2(6):102-111.
- 19. Mızrak S, Turan V, Inan S, et al. Effect of Nicotine on RANKL and OPG and Bone Mineral Density. J Invest Surg. 2014;27(6)327-331.
- 20. Susar H, Aycan K. Nikotinin Embriyonal Kemik Gelişimi Üzerindeki Teratojenik Etkisine Karşı E Vitamininin Koruyucu Rolü, Phd Thesis, Erciyes University, 2017. https://tez.yok.gov.tr/UlusalTezMerkezi/tezDetay.jsp?id=qiHiezOEio-GiMLDvHTy9w&no=B387_zfwUqbAIMeYXZJF6A. Accessed 01 April, 2023.
- 21. Canever L, Alves CS, Mastella G, et al. The Evaluation of Folic Acid-Deficient or Folic Acid-Supplemented Diet in the Gestational Phase of Female Rats and in Their Adult Offspring Subjected to an Animal Model of Schizophrenia. Mol Neurobiol. 2018;55(3):2301-2319.
- 22. Al-Gailani S. Making birth defects 'preventable': pre-conceptional vitamin supplements and the politics of risk reduction. Stud Hist Philos Biol Biomed Sci. 2014;47:278-289.
- 23. Mohammadi A, Omrani L, Omrani LR, et al. Protective Effect of Folic Acid on Cyclosporine-Induced Bone Loss in Rats. Transpl Int. 2012;25(1):127-133.
Effects Of Folic Acid Versus Nicotine On Bone Development
Year 2024,
Volume: 8 Issue: 1, 48 - 55, 29.04.2024
Kadirhan Doğan
,
Mehtap Nisari
,
Ahmet Payas
,
Tolga Ertekin
,
Hatice Güler
,
Özge Al
Abstract
Purpose: Nicotine exposure during pregnancy directly or indirectly harms not only the mother but also the fetal tissues. The aim of this study is to investigate the possible effects of folic acid given against nicotine used during pregnancy on bone development of fetuses.
Materials and Methods: 18 adult female rats were divided into control, low-dose nicotine (LDN), high-dose nicotine (HDN), low-dose nicotine + folic acid (LDN + FA), high-dose nicotine + folic acid (HDN + FA), and folic acid (FA) group equally. During 20 days, 1 ml/kg serum physiologic (SP) solution to the control group, 3 mg/kg nicotine to LDN, 6 mg/kg nicotine to HDN, 3 mg/kg nicotine and 400 µg/kg FA to LDN+FA, 6 mg/kg nicotine and 400 µg/kg FA to HDN+FA, 400 µg/kg FA to the FA group was administered. Bones of fetuses taken by cesarean section on the 20th day of pregnancy were stained with the bilateral skeleton staining technique. The stained anterior and posterior extremity bones were photographed under a stereomicroscope. Bone length, extent of ossification and percentage of ossification were measured. Statistical data were evaluated using the R programming language (v. 3.2.3).
Results: The bone development of LDN and HDN groups was significantly lower and LDN+FA and HDN+FA groups was close to the control group (p<0.05).
Conclusion: While nicotine used during pregnancy decreases the bone development of fetuses, FA may decrease this effect and increase ossification.
Supporting Institution
Erciyes University Scientific Research Project Unit.
Project Number
TYL-2016-6497
Thanks
We thank to Erciyes University Scientific Research Project Unit who financially supported this work.
References
- 1. Yılmaz H, Ertekin T, Atay E, et al. Antioxidant role of melatonin against nicotine’s teratogenic effects on embryonic bone development. Iran J Basic Med Sci. 2018;21(8):787-793.
- 2. Nisari M, Ulger H, Unur E, Karaca O, Ertekin T. Effect of interleukin 12 (IL-12) on embryonic development and yolk sac vascularisation. Bratisl Lek Listy. 2014;115(9):532-537.
- 3. Lugg ST, Scott A, Parekh D, Naidu B, Thickett DR. Cigarette smoke exposure and alveolar macrophages: mechanisms for lung disease. Thorax. 2022;77(1):94-101.
- 4. Callahan PM, Terry AV Jr, Peitsch MC, Hoeng J, Koshibu K. Differential effects of alkaloids on memory in rodents. Sci Rep. 2021;11(1):9843.
- 5. Yüce B, Tengiz Fİ. Effects of tobacco use during pregnancy on infant and child health. D J Med Sci. 2020;6(2):70-73.
- 6. Marinucci L, Bodo M, Balloni S, Locci P, Baroni T. Sub-toxic nicotine concentrations affect extracellular matrix and growth factor signaling gene expressions in human osteoblasts. J Cell Physiol. 2014;229(12):2038-2048.
- 7. Kirschneck C, Proff P, Maurer M, Reicheneder C, Römer P. Orthodontic forces add to nicotine-induced loss of periodontal bone: An in vivo and in vitro study. J Orofac Orthop. 2015;76(3):195-212.
- 8. Payas A, Ekinci Y, Gürbüz K, et al. Vitamin B12 reduces the negative effects of nicotine on fetal bone development in the rats. Jt Dis Relat Surg. 2022;33(1):216-224.
- 9. Manavi KR, Alston-Mills BP, Thompson MP. History of tobacco, vitamin D and women. Int J Vitam Nutr Res. 2020;90(5-6):389-394.
- 10. Shulpekova Y, Nechaev V, Kardasheva S, et al. The Concept of Folic Acid in Health and Disease. Molecules. 2021;26(12):3731.
- 11. Vajda FJE, O’Brien TJ, Graham JE, et al. Folic Acid dose, valproate and fetal malformations. Epilepsy&Behavior. 2021;114:107569.
- 12. Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-2611.
- 13. Booth M, Powell N, Corfield C, French JM. An automated technique for double staining of bone and cartilage in fetal mouse skeletal specimens using alizarin red S and Alcian blue. Biotech Histochem. 2022;97(3):222-227.
- 14. Dingerkus G, Uhler LD. Enzyme Clearing Of Alcian Blue Stained Whole Small Vertebrates For Demonstration Of Cartilage. Stain Technol. 1977;52(4):229-232.
- 15. Liao YJ, Tang PC, Chen LR, Yang JR. A protocol for differential staining of cartilages and ossified bones in fetal and adult mouse skeletons using alcian blue and alizarin red S. J Histotechnol. 2020;43(4):204-209.
- 16. Çetin E, Malas MA. Fetal Büyümeye Etki Eden Çevresel Faktörler. S.D.Ü. Tıp Fak. Derg. 2005;12(2):65-72.
- 17. Oruç Ş. Ratlarda Hamilelik Döneminde Verilen Nikotinin, Neonatal Dönemde Molar Dişler Üzerindeki Etkileri, Master Thesis, Dicle Üniversitesi; 1996. https://tez.yok.gov.tr/UlusalTezMerkezi/tezDetay.jsp?id=91qsG18yUN59V_N5VMHDKw&no=91qsG18yUN59V_N5VMHDKw. Accessed 01 April, 2023.
- 18. Patel RA, Wilson RF, Patel PA, Palmer RM. The Effect of Smoking On Bone Healing. Bone Joint Res. 2013;2(6):102-111.
- 19. Mızrak S, Turan V, Inan S, et al. Effect of Nicotine on RANKL and OPG and Bone Mineral Density. J Invest Surg. 2014;27(6)327-331.
- 20. Susar H, Aycan K. Nikotinin Embriyonal Kemik Gelişimi Üzerindeki Teratojenik Etkisine Karşı E Vitamininin Koruyucu Rolü, Phd Thesis, Erciyes University, 2017. https://tez.yok.gov.tr/UlusalTezMerkezi/tezDetay.jsp?id=qiHiezOEio-GiMLDvHTy9w&no=B387_zfwUqbAIMeYXZJF6A. Accessed 01 April, 2023.
- 21. Canever L, Alves CS, Mastella G, et al. The Evaluation of Folic Acid-Deficient or Folic Acid-Supplemented Diet in the Gestational Phase of Female Rats and in Their Adult Offspring Subjected to an Animal Model of Schizophrenia. Mol Neurobiol. 2018;55(3):2301-2319.
- 22. Al-Gailani S. Making birth defects 'preventable': pre-conceptional vitamin supplements and the politics of risk reduction. Stud Hist Philos Biol Biomed Sci. 2014;47:278-289.
- 23. Mohammadi A, Omrani L, Omrani LR, et al. Protective Effect of Folic Acid on Cyclosporine-Induced Bone Loss in Rats. Transpl Int. 2012;25(1):127-133.