The effect of Gallic acid on fetus viability and hippocampal cell damages in rat model of utreo-placental insufficiency

Authors
Mohammad Yousefi-Ghalati
Mohammad Amin Edalatmanesh
Department of Biology, College of Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran
Abstract
Introduction

Uteroplacental insufficiency (UPI) causes brain damage and neurodevelopmental deficits in intrauterine growth-restricted fetus. This study examined the effect of Gallic acid (GA) on fetus viability and weight of fetus, uterus, and placenta and hippocampal piramidal cell densityof fetus in UPI model.

Materials and Methods

25 pregnant Wistar rats were randomly divided into 5 groups: control, UPI+NS (Uteroplacental insufficiency + Normal saline), UPI+GA100 (Uteroplacental insufficiency + Gallic acid 100), UPI+GA200 (Uteroplacental insufficiency + Gallic acid 200) and UPI+GA400 (Uteroplacental insufficiency + Gallic acid 400). UPI induction is carried out by anterior uterine artery occlusion on gestation day (GD) 18. GA or normal saline was administrated by gavage method from GD15 to GD21. Then, on GD21 the fetus were cesarean section and after weighing, anesthetized by hypothermia, their heads were cut and the brains evaluated for histopathological studies.

Results

A significant increase in uterine weight and a significant decrease in fetal viability and cell density were observed in the hippocampal CA1, CA2 and CA3 subdivision in UPI+NS group compared to the control group (p˂0.05). On the other hand, viability rate, fetus weight and cell density in CA1 and CA3 subdivisions were significantly higher in the GA-treated groups than the UPI+NS group (p˂0.05).

Conclusion

GA reduced fetal mortality and fetal hippocampal cell damage in UPI model. Therefore, it usable to avoid the neurodevelopmental complications due to intrauterine growth restriction.
Keywords
Gallic acid
Fetal Growth Retardation
Brain injuries
Hippocampus
Fetal viability
1. Gumus HG, Illa M, Pla L, Zamora M, Crispi F, Gratacos E. Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction. PloS one. 2018;13(2):e0193240.
2. Figueras F, Caradeux J, Crispi F, Eixarch E, Peguero A, Gratacos E. Diagnosis and surveillance of late-onset fetal growth restriction. Am J Obstet Gynecol. 2018; 218: 790-802.
3. Illa M, Eixarch E, Batalle D, Arbat-Plana A, Muñoz-Moreno E, Figueras F, et al. Long-term functional outcomes and correlation with regional brain connectivity by MRI diffusion tractography metrics in a near-term rabbit model of intrauterine growth restriction. PloS one. 2013;8(10):e76453.
4. Sharma D, Sharma P, Shastri S. Genetic, metabolic and endocrine aspect of Intrauterine growth restriction: an update. J Matern Fetal Neonatal Med. 2016; 9:1-45.
5. Kady SM, Gardosi J. Perinatal mortality and fetal growth restriction. Best Pract Res Clin Obstet Gynaecol. 2004; 18: 397-410.
6. Fung C, Ke X, Brown AS, Yu X, McKnight RA, Lane RH. Uteroplacental insufficiency alters rat hippocampal cellular phenotype in conjunction with ErbB receptor expression. Pediatr Res. 2012; 72(1):2-9.
7. Limesand SW, Rozance PJ. Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency. J Physiol. 2017; 595(15):5103-13.
8. Schober ME, McKnight RA, Yu X, Callaway CW, Ke X, Lane RH. Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi. Am J Physiol Regul Integr Comp Physiol. 2009; 296(3):R681-92.
9. Wixey JA, Lee KM, Miller SM, Goasdoue K, Colditz PB, Tracey Bjorkman S, Chand KK. Neuropathology in intrauterine growth restricted newborn piglets is associated with glial activation and proinflammatory status in the brain. J Neuroinflammation. 2019; 16(1):5.
10. Rolls ET. Limbic systems for emotion and for memory, but no single limbic system. Cortex. 2015;62:119-57.
11. Li Y, Shen M, Stockton ME, Zhao X. Hippocampal deficits in neurodevelopmental disorders. Neurobiol Learn Mem. 2019; 165:106945.
12. Chen, Jieli, Chopp M. Neurorestorative treatment of stroke: cell and pharmacological approaches. NeuroRx. 2006; 3:466-73.
13. Eichenbaum H. Hippocampus: cognitive processes and neural representations that underlie declarative memory. Neuron. 2004; 44:109-20.
14. Raskin J, Cummings J, Hardy J, Schuh K, Dean RA. Neurobiology of Alzheimer's Disease: Integrated Molecular, Physiological, Anatomical, Biomarker, and Cognitive Dimensions.Curr Alzheimer Res. 2015; 12(8):712-22.
15. Kosuru RY, Roy A, Das SK, Bera S. Gallic Acid and Gallates in Human Health and Disease: Do Mitochondria Hold the Key to Success? Mol Nutr Food Res. 2018; 62(1).
16. Choubey S, Goyal S, Varughese LR, Kumar V. Probing Gallic Acid for Its Broad Spectrum Applications. Mini Rev Med Chem. 2018; 18(15):1283-93.
17. Kim MJ, Seong AR, Yoo JY, Jin CH, Lee YH, Kim YJ, et al. Gallic acid, a histone acetyltransferase inhibitor, suppresses β-amyloid neurotoxicity by inhibiting microglial-mediated neuroinflammation. Mol Nutr Food Res. 2011; 55(12):1798-808.
18. Briffa JF, O'Dowd R, Moritz KM, Romano T, Jedwab LR, McAinch AJ, et al. Uteroplacental insufficiency reduces rat plasma leptin concentrations and alters placental leptin transporters: ameliorated with enhanced milk intake and nutrition. J Physiol. 2017; 595(11):3389-407.
19. Moghadas M, Edalatmanesh MA, Robati R.Histopathological Analysis from Gallic Acid Administration on Hippocampal Cell Density, Depression, and Anxiety Related Behaviors in A Trimethyltin Intoxication Model. Cell J. 2016; 17(4):659-67.
20. Wixey JA, Chand KK, Colditz PB, Bjorkman ST. Review: Neuroinflammation in intrauterine growth restriction. Placenta. 2017; 54:117-24.
21. Krishna U, Bhalerao S. Placental insufficiency and fetal growth restriction. J Obstet Gynaecol India. 2011; 61(5):505-11.
22. Karowicz-Bilinska A, Kedziora-Kornatowska K, Bartosz G. Indices of oxidative stress in pregnancy with fetal growth restriction. Informa Health Care. 2007; 41:870–3.
23. Damodaram M, Story L, Eixarch E, Patel A, McGuinness A, Allsop J, et al. Placental MRI in fetal growth restriction. Placenta. 2010; 31(6):491–8.
24. Chang JL, Bashir M, Santiago C, Farrow K, Fung C, Brown AS, et al. Intrauterine Growth Restriction and Hyperoxia as a Cause of White Matter Injury. Dev Neurosci. 2018; 40(4):344-57.
25. Maliszewski-Hall AM, Alexander M, Tkáč I, Öz G, Rao R. Differential Effects of Intrauterine Growth Restriction on the Regional Neurochemical Profile of the Developing Rat Brain. Neurochem Res. 2017; 42(1):133-40.
26. Ruff CA, Faulkner SD, Rumajogee P, Beldick S, Foltz W, Corrigan J, et al. The extent of intrauterine growth restriction determines the severity of cerebral injury and neurobehavioural deficits in rodents. PLoS One. 2017; 12(9):e0184653.
27. Batalle D, Eixarch E, Figueras F, Muñoz-Moreno E, Bargallo N, Illa M, et al. Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome. Neuroimage. 2012; 60(2):1352-66.
28. Furuta M, Ninomiya-Baba M, Chiba S, Funabashi T, Akema T, Kunugi H. Exposure to social defeat stress in adolescence improves the working memory and anxiety-like behavior of adult female rats with intrauterine growth restriction, independently of hippocampal neurogenesis. Horm Behav. 2015; 70:30-7.
29. Baschat AA. Neurodevelopment after fetal growth restriction. Fetal Diagn Ther. 2014; 36(2):136-42.
30. Heazell AEP, Brown LM, Baker P, Crocker I. Expression of oncoproteins p53 and Mdm2 within trophoblast of normal and pre-eclamptic pregnancies. J Soc Gynecol Investig. 2005; 12:362.
31. Perez M, Robbins ME, Revhaug C, Saugstad OD.Oxygen radical disease in the newborn, revisited: Oxidative stress and disease in the newborn period. Free Radic Biol Med. 2019; 142:61-72.
32. Choubey S, Goyal S, Varughese LR, Kumar V. Probing Gallic Acid for Its Broad Spectrum Applications. Mini Rev Med Chem. 2018; 18(15):1283-93.
33. Mansouri MT, Farbood Y, Sameri MJ, Sarkaki A, Naghizadeh B, Rafeirad M. Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. Food Chem. 2013; 138(2-3):1028-33.
34. Doroodi L, Edalatmanesh MA. The Histopathological Evaluation of Gallic Acid on Rat Purkinje Cells after Trimethyltin Intoxication. Shefaye Khatam. 2017; 5(2) :11-8. [Persian]
35. Baziyar Y, Edalatmanesh MA, Hosseini SA, Zar A. The Effects of Endurance Training and Gallic Acid on BDNF and TNF-a in Male Rats with Alzheimer. IJAEP. 2017; 5(4):45-54.