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Abstract
Preeclampsia is hypertension in pregnancy that affects 2% to 8% of pregnancies worldwide and causes significant maternal and perinatal morbidity and mortality. In the pathogenesis of preeclampsia, placental hypoxia plays an important role, associated with excessive trophoblast apoptosis resulting in decreased trophoblast and spiral arteries invasion. This placental hypoxic condition will induce increased expression of Hypoxia Inducible Factor -1-Alpha (HIF-1-A). L-Arginine is a potent vasodilator presumably to improve preeclampsia placental hypoxic conditions and reduce HIF-1-A expression. This study was an experimental study with a parallel-group post-test only design. Thirty-six preeclamptic mice models were divided into 2 groups. The control group (K1) 18 preeclamptic mice model without treatment and the treatment group (K2) 18 preeclamptic mice given L-Arginine. The independent variable was the administration of L-Arginine and the dependent variable is the placental HIF-1-A expression. Statistical analysis used unpaired t-test on normal data distribution, and Mann Whitney test on abnormal data distribution. The mean of placental HIF-1-A expression K1 was 2.47 ± 1.65 with a minimum value of 0.4 and a maximum value of 6.6. At K2 0.93 ± 0.55 with a minimum value of 0.0 and a maximum value of 2.0. Statistical tests showed that the placental HIF-1-A expression in the treatment group was significantly lower than that in the control group (p <0.001). In conclusion, the expression of HIF-1-A in preeclamptic mice model placenta decreased with L-Arginine administration.
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References
- Al-Bayati M, Ahmad M, Khamas W (2014). The potential effect of L-arginine on mice placenta. Advances in Pharmacoeidemiology & Drug Safety 3, 1-9.
- Albers RE, Kaufman MR, Natale BV, et al (2019). Trophoblast-specific expression of hif-1α results in preeclampsia-like symptoms and fetal growth restriction. Sci Rep 9, 1-13.
- Casanell P, Escudero C, Sobrevia L (2007). Equilibrative nucleoside (ents) and cationic amino acid (cats) transporters: Implications in foetal endothelial dysfunction in human pregnancy diseases. Current Vascular Pharmacology 5, 69-84.
- Chen J, Gong X, Chen P, et al (2016). Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis. BMC Pregnancy and Childbirth 16, 1-20.
- Comiskey M, Warner CM, Schust DJ (2013). MHC molecules of the preimplantation embryo and trophoblast. Madame Curie Bioscience Database. Available from http://www.ncbi.nlm.nih. Accessed Dec 9, 2020.
- Facchinett F, Farulla A (2017). Dietary supplements and drugs for preeclampsia prophylaxis. Journal of Women's Cardiovascular Health 7, 59.
- Garford KL, Andraweera PH, Roberts CT, et al (2020). Animal models of preeclampsia: Causes, consequences, and interventions. Hypertension 75, 1363-1381.
- Gathiram P, Moodley J (2016). Preeclampsia: Its pathogenesis and pathophysiology. Cardiovascular Journal of Africa 27, 71-8.
- Holwerda KM, Faas MM, van Goor H, et al (2013). A solution for the therapeutic dilemma in preeclampsia?. Hypertension 62, 653-659.
- Kedia K, Smith SF, Wright AH, et al (2016). Global ‘omics' evaluation of human placental responses to preeclamptic conditions. Am J Obstet Gynecol 215, 1-25.
- Kooffreh ME, Ekott M, Ekpoudom DO (2014). The prevalence of preeclampsia among pregnant women in the University of Calabar Teaching Hospital, Calabar. Saudi J Health Sci 3, 133-136.
- Kosovic I, Prusac IK, Mestrovic Z, et al (2020). HIF- 1α immunohistochemical expression in decidual cells, villous and extravillous trophoblast in placentas from pregnancies complicated with preeclampsia. Pregnancy Hypertension 21, 176-178.
- Kurokawa H, Ito H, Terasaki M, et al. (2019). Nitric oxide regulates the expression of heme carrier protein-1 via hypoxia inducible factor-1α stabilization. PLoS One 14, 1-19.
- Rezky DM, Navianti D, Nurhayati N (2020). Gambaran proteinuria pada ibu hamil trimester III di rumah sakit kota palembang tahun 2019. Journal of Indonesian Medical Laboratory and Science 1, 32-47.
- Sirenden H, Sunarno I, Usman AN, et al (2020). Deficiency of serum L-Arginin levels in severe preeclampsia; a consideration for supplementation. 30, 566-9.
- Soetrisno SS, Wibowo A (2017). L-Arginin improves uterine spiral arterial wall thickness in mouse models of preeclampsia. Universa Medicina 36, 131-138.
- Uzan J, Carbonnel M. (2011). Preeclampsia: Pathophysiology, diagnosis and management. Vasc Health Risk Manag 7, 467-474.
- Vadillo-Ortega Felipe, Perichart-Perera O, Espino S, et al (2011). Effect of supplementation during pregnancy with L- arginin and antioxidant vitamins in medical food on preeclampsia in high-risk population: Randomized controlled trial. BMJ 342, 1-8.
- Zhang Z, Huang C, Wang P, et al (2020). HIF-1α affects trophoblastic apoptosis involved in the onset of preeclampsia by regulating FOXO3a under hypoxic conditions. Mol Med Rep 21, 2484-2492
References
Al-Bayati M, Ahmad M, Khamas W (2014). The potential effect of L-arginine on mice placenta. Advances in Pharmacoeidemiology & Drug Safety 3, 1-9.
Albers RE, Kaufman MR, Natale BV, et al (2019). Trophoblast-specific expression of hif-1α results in preeclampsia-like symptoms and fetal growth restriction. Sci Rep 9, 1-13.
Casanell P, Escudero C, Sobrevia L (2007). Equilibrative nucleoside (ents) and cationic amino acid (cats) transporters: Implications in foetal endothelial dysfunction in human pregnancy diseases. Current Vascular Pharmacology 5, 69-84.
Chen J, Gong X, Chen P, et al (2016). Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis. BMC Pregnancy and Childbirth 16, 1-20.
Comiskey M, Warner CM, Schust DJ (2013). MHC molecules of the preimplantation embryo and trophoblast. Madame Curie Bioscience Database. Available from http://www.ncbi.nlm.nih. Accessed Dec 9, 2020.
Facchinett F, Farulla A (2017). Dietary supplements and drugs for preeclampsia prophylaxis. Journal of Women's Cardiovascular Health 7, 59.
Garford KL, Andraweera PH, Roberts CT, et al (2020). Animal models of preeclampsia: Causes, consequences, and interventions. Hypertension 75, 1363-1381.
Gathiram P, Moodley J (2016). Preeclampsia: Its pathogenesis and pathophysiology. Cardiovascular Journal of Africa 27, 71-8.
Holwerda KM, Faas MM, van Goor H, et al (2013). A solution for the therapeutic dilemma in preeclampsia?. Hypertension 62, 653-659.
Kedia K, Smith SF, Wright AH, et al (2016). Global ‘omics' evaluation of human placental responses to preeclamptic conditions. Am J Obstet Gynecol 215, 1-25.
Kooffreh ME, Ekott M, Ekpoudom DO (2014). The prevalence of preeclampsia among pregnant women in the University of Calabar Teaching Hospital, Calabar. Saudi J Health Sci 3, 133-136.
Kosovic I, Prusac IK, Mestrovic Z, et al (2020). HIF- 1α immunohistochemical expression in decidual cells, villous and extravillous trophoblast in placentas from pregnancies complicated with preeclampsia. Pregnancy Hypertension 21, 176-178.
Kurokawa H, Ito H, Terasaki M, et al. (2019). Nitric oxide regulates the expression of heme carrier protein-1 via hypoxia inducible factor-1α stabilization. PLoS One 14, 1-19.
Rezky DM, Navianti D, Nurhayati N (2020). Gambaran proteinuria pada ibu hamil trimester III di rumah sakit kota palembang tahun 2019. Journal of Indonesian Medical Laboratory and Science 1, 32-47.
Sirenden H, Sunarno I, Usman AN, et al (2020). Deficiency of serum L-Arginin levels in severe preeclampsia; a consideration for supplementation. 30, 566-9.
Soetrisno SS, Wibowo A (2017). L-Arginin improves uterine spiral arterial wall thickness in mouse models of preeclampsia. Universa Medicina 36, 131-138.
Uzan J, Carbonnel M. (2011). Preeclampsia: Pathophysiology, diagnosis and management. Vasc Health Risk Manag 7, 467-474.
Vadillo-Ortega Felipe, Perichart-Perera O, Espino S, et al (2011). Effect of supplementation during pregnancy with L- arginin and antioxidant vitamins in medical food on preeclampsia in high-risk population: Randomized controlled trial. BMJ 342, 1-8.
Zhang Z, Huang C, Wang P, et al (2020). HIF-1α affects trophoblastic apoptosis involved in the onset of preeclampsia by regulating FOXO3a under hypoxic conditions. Mol Med Rep 21, 2484-2492