Evaluation of the mixture "MagSelDex" for neuroprotection against offspring brain injury in endotoxin-induced chorioamnionitis: A Preliminary Study
Abstract
Objective: Chorioamnionitis resulting from preterm labor leads to concurrent damage in both the placenta and fetal brain. This study aims to explore the impact of incorporating antioxidants and anti-inflammatory agents, specifically selenium (Sel) and dexpanthenol (Dex), into the standard magnesium (Mg) regimen, in mitigating this damage.
Materials and Methods: A total of six pregnant rats were assigned to six distinct groups: control, lipopolysaccharide (LPS) (1 mg/kg, single intraperitoneal dose on day 17), Mg (60 mg/kg Mg, intraperitoneal), Mg+Sel (1 mg/kg, intraperitoneal), Mg+Dex (500 mg/kg, intraperitoneal), and Mg+Sel+Dex. On the 17th day of pregnancy, fetal brain and placenta tissues were harvested for histopathological examination and immunohistochemical evaluation of tumor necrosis factor-alpha (TNF-α) and neurofilament expression.
Results: The histopathological assessment revealed LPS-induced hemorrhage and mild inflammatory cell infiltration in the placenta, and pronounced hyperemia along with minor hemorrhage in the fetal brain. The LPS group exhibited significantly elevated TNF-α expression in both placenta and fetal brain, coupled with reduced neurofilament expression in the fetal brain. In contrast, the groups treated with Mg alone and the combined Sel and Dex therapy exhibited moderate to substantial improvement in pathological findings across both tissues. The most notable enhancement was observed in the Mg+Sel+Dex group.
Conclusion: Administration of Mg as a standalone treatment and the coadministration of Sel and Dex effectively shielded the placenta and fetal brain from LPS-triggered chorioamnionitis. However, the most prominent protective effect was observed in the Mg+Sel+Dex group.
Project Number
TSG-2022-8783
References
- 1. Burdet J, Rubio AP, Salazar AI, Ribeiro ML, Ibarra C, Franchi AM. Inflammation, infection and preterm birth. Curr Pharm Des. 2014;20(29):4741-4748. doi:10.2174/1381612820666140130202224
- 2. Gotsch F, Romero R, Kusanovic JP, et al. The fetal inflammatory response syndrome. Clin Obstet Gynecol. 2007;50(3):652-683. doi:10.1097/GRF.0b013e31811ebef6
- 3. Romero R, Chaiworapongsa T, Espinoza J. Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J Nutr. 2003;133(5 Suppl 2):1668S-1673S. doi:10.1093/jn/133.5.1668S
- 4. Badawi N, Mcintyre S, Hunt RW. Perinatal care to prevent cerebral palsy. Dev Med Child Neurol. 2021;63(2):156-161. doi:10.1111/dmcn.14754
- 5. Kany S, Vollrath JT, Relja B. Cytokines in Inflammatory Disease. Int J Mol Sci. 2019;20(23):6008. Published 2019 Nov 28. doi:10.3390/ijms20236008
- 6. Kenyon S, Pike K, Jones DR, et al. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial. Lancet. 2008;372(9646):1319-1327. doi:10.1016/S0140-6736(08)61203-9
- 7. Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res. 1997;42(1):1-8. doi:10.1203/00006450-199707000-00001
- 8. Burd I, Breen K, Friedman A, Chai J, Elovitz MA. Magnesium sulfate reduces inflammation-associated brain injury in fetal mice [published correction appears in Am J Obstet Gynecol. 2010 Jun;202(6):603]. Am J Obstet Gynecol. 2010;202(3):292.e1-292.e2929. doi:10.1016/j.ajog.2010.01.022
- 9. Marchioni RM, Lichtenstein GR. Tumor necrosis factor-α inhibitor therapy and fetal risk: a systematic literature review. World J Gastroenterol. 2013;19(17):2591-2602. doi:10.3748/wjg.v19.i17.2591
- 10. Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009;(1):CD004661. Published 2009 Jan 21. doi:10.1002/14651858.CD004661.pub3
- 11. Nguyen TM, Crowther CA, Wilkinson D, Bain E. Magnesium sulphate for women at term for neuroprotection of the fetus. Cochrane Database Syst Rev. 2013;(2):CD009395. Published 2013 Feb 28. doi:10.1002/14651858.CD009395.pub2
- 12. Scheans P. The role of magnesium sulfate in the prevention of cerebral palsy. Neonatal Netw. 2012;31(2):121-124. doi:10.1891/0730-0832.31.2.121
- 13. Berger R, Söder S. Neuroprotection in preterm infants. Biomed Res Int. 2015;2015:257139. doi:10.1155/2015/257139
- 14. Chang E. Preterm birth and the role of neuroprotection. BMJ. 2015;350:g6661. Published 2015 Jan 20. doi:10.1136/bmj.g6661
- 15. Bekheet SH. Comparative effects of repeated administration of cadmium chloride during pregnancy and lactation and selenium protection against cadmium toxicity on some organs in immature rats' offsprings. Biol Trace Elem Res. 2011;144(1-3):1008-1023. doi:10.1007/s12011-011-9084-z
- 16. Silva I, Bracchi I, Keating E. The association between selenium levels and hypertensive disorders of pregnancy: a systematic review of the literature. Br J Nutr. 2023;130(4):651-665. doi:10.1017/S0007114522003671
- 17. Albrakati A, Alsharif KF, Al Omairi NE, et al. Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities. Int J Nanomedicine. 2021;16:8447-8464. Published 2021 Dec 30. doi:10.2147/IJN.S323436
- 18. Cagin YF, Parlakpinar H, Vardi N, et al. Effects of dexpanthenol on acetic acid-induced colitis in rats. Exp Ther Med. 2016;12(5):2958-2964. doi:10.3892/etm.2016.3728
- 19. Li L, Feng L, Jiang WD, et al. Dietary pantothenic acid depressed the gill immune and physical barrier function via NF-κB, TOR, Nrf2, p38MAPK and MLCK signaling pathways in grass carp (Ctenopharyngodon idella). Fish Shellfish Immunol. 2015;47(1):500-510. doi:10.1016/j.fsi.2015.09.038
- 20. Yavuz A, Sezik M, Ozmen O, Asci H. Fingolimod against endotoxin-induced fetal brain injury in a rat model. J Obstet Gynaecol Res. 2017;43(11):1708-1713. doi:10.1111/jog.13444
- 21. Zheng J, Tian M, Liu L, Jia X, Sun M, Lai Y. Magnesium sulfate reduces vascular endothelial cell apoptosis in rats with preeclampsia via the miR-218-5p/HMGB1 pathway. Clin Exp Hypertens. 2022;44(2):159-166. doi:10.1080/10641963.2021.2013492
- 22. Yousuf S, Atif F, Ahmad M, et al. Selenium plays a modulatory role against cerebral ischemia-induced neuronal damage in rat hippocampus. Brain Res. 2007;1147:218-225. doi:10.1016/j.brainres.2007.01.143
- 23. Tepebaşı MY, Büyükbayram Hİ, Özmen Ö, Taşan Ş, Selçuk E. Dexpanthenol ameliorates doxorubicin-induced lung injury by regulating endoplasmic reticulum stress and apoptosis. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(8):1837-1845. doi:10.1007/s00210-023-02497-3
- 24. Samuel TM, Sakwinska O, Makinen K, Burdge GC, Godfrey KM, Silva-Zolezzi I. Preterm Birth: A Narrative Review of the Current Evidence on Nutritional and Bioactive Solutions for Risk Reduction. Nutrients. 2019;11(8):1811. Published 2019 Aug 6. doi:10.3390/nu11081811
- 25. Galson SK. Preterm birth as a public health initiative. Public Health Rep. 2008;123(5):548-550. doi:10.1177/003335490812300502
- 26. Wang P, Zhu G, Wu Q, et al. Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia. FASEB J. 2023;37(4):e22834. doi:10.1096/fj.202201546RR
- 27. Soares JB, Pimentel-Nunes P, Roncon-Albuquerque R, Leite-Moreira A. The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases. Hepatol Int. 2010;4(4):659-672. Published 2010 Oct 21. doi:10.1007/s12072-010-9219-x
- 28. Simões LR, Sangiogo G, Tashiro MH, et al. Maternal immune activation induced by lipopolysaccharide triggers immune response in pregnant mother and fetus, and induces behavioral impairment in adult rats. J Psychiatr Res. 2018;100:71-83. doi:10.1016/j.jpsychires.2018.02.007
- 29. Serhan CN. Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms. FASEB J. 2017;31(4):1273-1288. doi:10.1096/fj.201601222R
- 30. Walani SR. Global burden of preterm birth. Int J Gynaecol Obstet. 2020;150(1):31-33. doi:10.1002/ijgo.13195
- 31. Motavaf M, Piao X. Oligodendrocyte Development and Implication in Perinatal White Matter Injury. Front Cell Neurosci. 2021;15:764486. Published 2021 Nov 4. doi:10.3389/fncel.2021.764486
- 32. van Tilborg E, de Theije CGM, van Hal M, et al. Origin and dynamics of oligodendrocytes in the developing brain: Implications for perinatal white matter injury. Glia. 2018;66(2):221-238. doi:10.1002/glia.23256
Bakteriyel endotoksin kaynaklı koryoamniyonitte fetal beyin hasarına karşı "MagSelDex" karışımının nöroprotektif etkilerinin değerlendirilmesi: Ön Çalışma
Abstract
Amaç: Preterm doğum kaynaklı koryoamnionitin plasenta ve fetal beyinde eş zamanlı hasara neden olduğu bilinmektedir. Bu çalışma, standart magnezyum (Mg) rejimine antioksidan ve anti-inflamatuar ajanlar olan selenyum (Sel) ve dekspantenol (Dex) eklemenin, bu hasarı hafifletmedeki etkisini araştırmayı amaçlamaktadır.
Gereç ve Yöntem: Toplam altı gebe sıçan, altı ayrı gruba ayrılmıştır: kontrol, lipopolisakkarit (LPS) (1 mg/kg, 17. gün tek doz intraperitoneal uygulama), Mg (60 mg/kg, intraperitoneal), Mg+Sel (1 mg/kg, intraperitoneal), Mg+Dex (500 mg/kg, intraperitoneal) ve Mg+Sel+Dex. Gebeliğin 17. gününde fetal beyin ve plasenta dokuları histopatolojik inceleme ile tümör nekroz faktör-alfa (TNF-α) ve nörofilament (NF) ekspresyonlarının immünohistokimyasal değerlendirmesi için toplandı.
Bulgular: Histopatolojik değerlendirme, plasentada LPS kaynaklı kanama ve hafif inflamatuar hücre infiltrasyonunu ortaya çıkardı; aynı zamanda fetal beyinde belirgin hiperemi ve hafif kanama görüldü. LPS grubunda, hem plasenta hem de fetal beyinde belirgin şekilde yükselmiş TNF-α ekspresyonu ve fetal beyinde azalmış NF ekspresyonu gözlendi. Bunun aksine, yalnızca Mg ile tedavi edilen gruplar ve birlikte uygulanan Sel ve Dex tedavisi, her iki dokuda da patolojik bulgularda düzelme sergiledi. En dikkate değer iyileşme Mg+Sel+Dex grubunda gözlendi.
Sonuç: Mg’ nin tek başına uygulanması ve Sel ile Dex' in birlikte uygulanması, plasentayı ve fetal beyini LPS ile indüklenmiş koryoamniyonitten etkili bir şekilde korudu. Ancak, en belirgin koruyucu etki Mg+Sel+Dex grubunda gözlemlendi.
Supporting Institution
Süleyman Demirel Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi
Project Number
TSG-2022-8783
References
- 1. Burdet J, Rubio AP, Salazar AI, Ribeiro ML, Ibarra C, Franchi AM. Inflammation, infection and preterm birth. Curr Pharm Des. 2014;20(29):4741-4748. doi:10.2174/1381612820666140130202224
- 2. Gotsch F, Romero R, Kusanovic JP, et al. The fetal inflammatory response syndrome. Clin Obstet Gynecol. 2007;50(3):652-683. doi:10.1097/GRF.0b013e31811ebef6
- 3. Romero R, Chaiworapongsa T, Espinoza J. Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J Nutr. 2003;133(5 Suppl 2):1668S-1673S. doi:10.1093/jn/133.5.1668S
- 4. Badawi N, Mcintyre S, Hunt RW. Perinatal care to prevent cerebral palsy. Dev Med Child Neurol. 2021;63(2):156-161. doi:10.1111/dmcn.14754
- 5. Kany S, Vollrath JT, Relja B. Cytokines in Inflammatory Disease. Int J Mol Sci. 2019;20(23):6008. Published 2019 Nov 28. doi:10.3390/ijms20236008
- 6. Kenyon S, Pike K, Jones DR, et al. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial. Lancet. 2008;372(9646):1319-1327. doi:10.1016/S0140-6736(08)61203-9
- 7. Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res. 1997;42(1):1-8. doi:10.1203/00006450-199707000-00001
- 8. Burd I, Breen K, Friedman A, Chai J, Elovitz MA. Magnesium sulfate reduces inflammation-associated brain injury in fetal mice [published correction appears in Am J Obstet Gynecol. 2010 Jun;202(6):603]. Am J Obstet Gynecol. 2010;202(3):292.e1-292.e2929. doi:10.1016/j.ajog.2010.01.022
- 9. Marchioni RM, Lichtenstein GR. Tumor necrosis factor-α inhibitor therapy and fetal risk: a systematic literature review. World J Gastroenterol. 2013;19(17):2591-2602. doi:10.3748/wjg.v19.i17.2591
- 10. Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009;(1):CD004661. Published 2009 Jan 21. doi:10.1002/14651858.CD004661.pub3
- 11. Nguyen TM, Crowther CA, Wilkinson D, Bain E. Magnesium sulphate for women at term for neuroprotection of the fetus. Cochrane Database Syst Rev. 2013;(2):CD009395. Published 2013 Feb 28. doi:10.1002/14651858.CD009395.pub2
- 12. Scheans P. The role of magnesium sulfate in the prevention of cerebral palsy. Neonatal Netw. 2012;31(2):121-124. doi:10.1891/0730-0832.31.2.121
- 13. Berger R, Söder S. Neuroprotection in preterm infants. Biomed Res Int. 2015;2015:257139. doi:10.1155/2015/257139
- 14. Chang E. Preterm birth and the role of neuroprotection. BMJ. 2015;350:g6661. Published 2015 Jan 20. doi:10.1136/bmj.g6661
- 15. Bekheet SH. Comparative effects of repeated administration of cadmium chloride during pregnancy and lactation and selenium protection against cadmium toxicity on some organs in immature rats' offsprings. Biol Trace Elem Res. 2011;144(1-3):1008-1023. doi:10.1007/s12011-011-9084-z
- 16. Silva I, Bracchi I, Keating E. The association between selenium levels and hypertensive disorders of pregnancy: a systematic review of the literature. Br J Nutr. 2023;130(4):651-665. doi:10.1017/S0007114522003671
- 17. Albrakati A, Alsharif KF, Al Omairi NE, et al. Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities. Int J Nanomedicine. 2021;16:8447-8464. Published 2021 Dec 30. doi:10.2147/IJN.S323436
- 18. Cagin YF, Parlakpinar H, Vardi N, et al. Effects of dexpanthenol on acetic acid-induced colitis in rats. Exp Ther Med. 2016;12(5):2958-2964. doi:10.3892/etm.2016.3728
- 19. Li L, Feng L, Jiang WD, et al. Dietary pantothenic acid depressed the gill immune and physical barrier function via NF-κB, TOR, Nrf2, p38MAPK and MLCK signaling pathways in grass carp (Ctenopharyngodon idella). Fish Shellfish Immunol. 2015;47(1):500-510. doi:10.1016/j.fsi.2015.09.038
- 20. Yavuz A, Sezik M, Ozmen O, Asci H. Fingolimod against endotoxin-induced fetal brain injury in a rat model. J Obstet Gynaecol Res. 2017;43(11):1708-1713. doi:10.1111/jog.13444
- 21. Zheng J, Tian M, Liu L, Jia X, Sun M, Lai Y. Magnesium sulfate reduces vascular endothelial cell apoptosis in rats with preeclampsia via the miR-218-5p/HMGB1 pathway. Clin Exp Hypertens. 2022;44(2):159-166. doi:10.1080/10641963.2021.2013492
- 22. Yousuf S, Atif F, Ahmad M, et al. Selenium plays a modulatory role against cerebral ischemia-induced neuronal damage in rat hippocampus. Brain Res. 2007;1147:218-225. doi:10.1016/j.brainres.2007.01.143
- 23. Tepebaşı MY, Büyükbayram Hİ, Özmen Ö, Taşan Ş, Selçuk E. Dexpanthenol ameliorates doxorubicin-induced lung injury by regulating endoplasmic reticulum stress and apoptosis. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(8):1837-1845. doi:10.1007/s00210-023-02497-3
- 24. Samuel TM, Sakwinska O, Makinen K, Burdge GC, Godfrey KM, Silva-Zolezzi I. Preterm Birth: A Narrative Review of the Current Evidence on Nutritional and Bioactive Solutions for Risk Reduction. Nutrients. 2019;11(8):1811. Published 2019 Aug 6. doi:10.3390/nu11081811
- 25. Galson SK. Preterm birth as a public health initiative. Public Health Rep. 2008;123(5):548-550. doi:10.1177/003335490812300502
- 26. Wang P, Zhu G, Wu Q, et al. Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia. FASEB J. 2023;37(4):e22834. doi:10.1096/fj.202201546RR
- 27. Soares JB, Pimentel-Nunes P, Roncon-Albuquerque R, Leite-Moreira A. The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases. Hepatol Int. 2010;4(4):659-672. Published 2010 Oct 21. doi:10.1007/s12072-010-9219-x
- 28. Simões LR, Sangiogo G, Tashiro MH, et al. Maternal immune activation induced by lipopolysaccharide triggers immune response in pregnant mother and fetus, and induces behavioral impairment in adult rats. J Psychiatr Res. 2018;100:71-83. doi:10.1016/j.jpsychires.2018.02.007
- 29. Serhan CN. Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms. FASEB J. 2017;31(4):1273-1288. doi:10.1096/fj.201601222R
- 30. Walani SR. Global burden of preterm birth. Int J Gynaecol Obstet. 2020;150(1):31-33. doi:10.1002/ijgo.13195
- 31. Motavaf M, Piao X. Oligodendrocyte Development and Implication in Perinatal White Matter Injury. Front Cell Neurosci. 2021;15:764486. Published 2021 Nov 4. doi:10.3389/fncel.2021.764486
- 32. van Tilborg E, de Theije CGM, van Hal M, et al. Origin and dynamics of oligodendrocytes in the developing brain: Implications for perinatal white matter injury. Glia. 2018;66(2):221-238. doi:10.1002/glia.23256
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmacology and Pharmaceutical Sciences (Other) |
| Journal Section | Araştırma Articlesi |
| Authors | |
| Project Number | TSG-2022-8783 |
| Publication Date | April 22, 2024 |
| Submission Date | August 24, 2023 |
| Published in Issue | Year 2024 Volume: 15 Issue: 1 |
Cite
SDÜ Sağlık Bilimleri Dergisi, makalenin gönderilmesi ve yayınlanması dahil olmak üzere hiçbir aşamada herhangi bir ücret talep etmemektedir. Dergimiz, bilimsel araştırmaları okuyucuya ücretsiz sunmanın bilginin küresel paylaşımını artıracağı ilkesini benimseyerek, içeriğine anında açık erişim sağlamaktadır.