Effect of Pravastatin on Levels of Malondealdehyde (MDA) And Endothelin-1 (ET-1) Preeclampsia Model Rats
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Abstract
Introduction: Pravastatin is known to have a number of pleiotropic effects including reducing endothelial dysfunc- tion, anti-inflammatory, antioxidants, conangiogenic, and antitrombotic. Pravastatin through the pleitropic effect is expected to be one of the alternative therapies to prevent preeclampsia. The limited strategy for prevention and treatment of preeclampsia is due to the unknown etiology and pathogenesis. These two markers are thought to contribute to the occurrence of preeclampsia although they cause it in two different pathways. MDA is a marker of oxidative stress as an end product of lipid peroxidation. ET-1 is a vasoconstrictor that plays a role in the pathogenesis of preeclampsia through increasing anti-angiogenic properties. Aim: to determine the effect of pravastatin on serum levels of MDA and ET-1 in preeclampsia rat models. Methods: This study consisted of 5 groups; negative control/ K(-) consisted of normal pregnant rats, positive control/ K(+) consisted of rat model of preeclampsia (rat model of pre- eclampsia induced by administration of L-NAME at a dose of 125 mg/kg BW/day since gestational age 13-19 days), treatment groups 1, 2, and 3 (rat model of preeclampsia given pravastatin with 3 different doses; 2 mg/day (P1), 4 mg/day (P2) and 8 mg/day(P3)) at 13-19 days of gestation. The rat model of preeclampsia was determined based on blood pressure > 140/90 with urine protein > +1. After termination, blood was drawn to measure serum MDA and ET-1 levels. Results: Serum levels of MDA and ET-1 were decreased in groups P2 and P3 compared to groups K(+). Statistically, there was a significant difference in the mean levels of MDA (p=0.001) and ET-1 (p=0.000) between each group. Conclusion: Pravastatin can prevent preeclampsia by decreasing MDA and ET-1.
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Yang S, Song L, Shi X, Zhao N, Ma Y. Ameliorative effects of pre-eclampsia by quercetin supplement to aspirin in a rat model induced by L-NAME. Biomed Pharmacother [Internet]. 2019;116(May):108969. doi:10.1016/j.biopha.2019.108969
de Lucca L, Rodrigues F, Jantsch LB, Kober H, Neme WS, Gallarreta FMP, et al. Delta-aminolevulinate dehydratase activity and oxidative stress markers in preeclampsia. Biomed Pharmacother [Internet]. 2016;84:224–9. doi:10.1016/j. biopha.2016.09.033
Fisher SJ. Why is placentation abnormal in preeclampsia? Am J Obstet Gynecol. 2015;213(4):S115–22. doi: 10.1016/j. ajog.2015.08.042.
Jena MK, Sharma NR, Petitt M, Maulik D, Nayak NR. Pathogenesis of preeclampsia and therapeutic approaches targeting the placenta. Biomolecules. 2020;10(6):1–28. doi: 10.3390/biom10060953.
Karacay Ö, Sepici-Dincel A, Karcaaltincaba D, Sahin D, Yalvaç S, Akyol M, et al. A quantitative evaluation of total antioxidant status and oxidative stress markers in preeclampsia and gestational diabetic patients in 24-36 weeks of gestation. Diabetes Res Clin Pract. 2010;89(3):231–8. doi: 10.1016/j.diabres.2010.04.015.
Taravati A, Tohidi F. Comprehensive analysis of oxidative stress markers and antioxidants status in preeclampsia. Taiwan J Obstet Gynecol [Internet]. 2018;57(6):779–90. doi:10.1016/j. tjog.2018.10.002
Sahay AS, Sundrani DP, Wagh GN, Mehendale SS, Joshi SR. International Journal of Gynecology and Obstetrics Regional differences in the placental levels of oxidative stress markers in pre-eclampsia. Int J Gynecol Obstet [Internet]. 2015;1–6. doi:10.1016/j.ijgo.2015.03.001
Giera M, Lingeman H, Niessen WMA. Recent advancements in the LC- and GC-based analysis of malondialdehyde (MDA): A brief overview. Chromatographia. 2012;75(9–10):433–40. doi: 10.1007/s10337-012-2237-1
Genc H, Uzun H, Benian A, Simsek G, Gelisgen R, Madazli R, et al. Evaluation of oxidative stress markers in first trimester for assessment of preeclampsia risk. Arch Gynecol Obstet. 2011;284(6):1367–73. doi: 10.1007/s00404-011-1865-2.
Gohil JT, Patel PK, Priyanka G. Evaluation of oxidative stress and antioxidant defence in subjects of preeclampsia. J Obstet Gynecol India. 2011;61(6):638–40. doi: 10.1007/s13224-011-0094-8
Can M, Guven B, Bektas S, Arikan I. Oxidative stress and apoptosis in preeclampsia. Tissue Cell [Internet]. 2014;46(6):477–81. doi:10.1016/j. tice.2014.08.004
Bakacak M, Kılınç M, Serin S, Ercan Ö, Köstü B, Avcı F, et al. Changes in copper, Zinc, and malondialdehyde levels and superoxide dismutase activities in pre-eclamptic pregnancies. Med Sci Monit. 2015;21:2414–20. doi: 10.12659/ MSM.895002.
HM. Al-Kuraishy, AI. Al-Gareeb TA. Concept and connotation of oxidative stress in preeclampsia. J Lab Physicians. 2018;10(3):276–82. doi: 10.4103/ JLP.JLP_26_18.
George EM, Granger JP. Endothelin: key mediator of hypertension in preeclampsia. Am J Hypertens. 2011;24(9):964–9. doi: 10.1038/ajh.2011.99
Emmanuel Bujold, Stéphanie Roberge, Lacasse et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol 2010; 116(2 Pt 1):402-414. doi: 10.1097/ AOG.0b013e3181e9322a.
Conde-agudelo A, Romero R, Kusanovic JP, Hassan SS. Supplementation with vitamins C and E during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes : a systematic review and metaanalysis. YMOB. 2011;204(6):503.e1-503.e12. doi: 10.1016/j. ajog.2011.02.020.
Wang C-Y, Liu P-Y, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med. 2008;14(1):37–44. doi: 10.1016/j.molmed.2007.11.004.
Katsi V, Georgountzos G, Kallistratos MS, Zerdes I, Makris T, Manolis AJ, et al. The role of statins in prevention of preeclampsia: a promise for the future? Front Pharmacol. 2017;8:247. doi: 10.3389/fphar.2017.00247
Huai J, Yang Z, Yi YH, Wang GJ. Different Effects of Pravastatin on Preeclampsia-like Symptoms in Different Mouse Models. Chin Med J (Engl). 2018;131(4):461–70. doi: 10.4103/0366- 6999.225058.
Carrepeiro MM, Rogero MM, Bertolami MC, Botelho PB, Castro N, Castro IA. Effect of n-3 fatty acids and statins on oxidative stress in statin-treated hypercholestorelemic and normocholesterolemic women. Atherosclerosis. 2011;217(1):171–8. doi:10.1016/j.atherosclerosis.2010.12.013
Xuan RR, Niu TT, Chen HM. Astaxanthin blocks preeclampsia progression by suppressing oxidative stress and inflammation. Mol Med Rep. 2016;14(3):2697–704. doi: 10.3892/ mmr.2016.5569
Shu WEN, Li H, Gong H, Zhang M, Niu X, Ma Y, et al. Evaluation of blood vessel injury, oxidative stress and circulating inflammatory factors in an L-NAME-induced preeclampsia-like rat model. Exp Ther Med. 2018;16(2):585–94. doi: 10.3892/ etm.2018.6217
Talebianpoor MS, Mirkhani H. The Effect of Tempol Administration on the Aortic Contractile Responses in Rat Preeclampsia Model. ISRN Pharmacol. 2012;2012:1–8. doi: 10.5402/2012/187208
Rahardjo B, Rahmawati W, Rahasti A, Retnaningrum DN, Sujuti H, As N, et al. The effect of extra virgin olive oil to decrease HSP-90, TNF-α and ET-1, in pre-eclampsia rat model. J Glob Pharma Technol. 2020;12(1):261–8.
Girardi G. Pravastatin to treat and prevent preeclampsia. Preclinical and clinical studies. J Reprod Immunol [Internet]. 2017;124(July):15–20. doi:10.1016/j.jri.2017.09.009
Sones JL, Davisson RL. Preeclampsia, of mice and women. Physiol Genomics. 2016;48(8):565–72. doi:10.1152/physiolgenomics.00125.2015.
Sircar M, Thadhani R, Karumanchi SA. Pathogenesis of preeclampsia. Curr Opin Nephrol Hypertens. 2015;24(2):131–8. doi: 10.1097/ MNH.0000000000000105.
Granger JP, Spradley FT, Bakrania BA. The endothelin system: a critical player in the pathophysiology of preeclampsia. Curr Hypertens Rep. 2018;20(4):1–8. doi: 10.1007/s11906-018- 0828-4.
Li F, Kakoki M, Smid M, Boggess K, Wilder J, Hiller S, et al. Causative effects of genetically determined high maternal/fetal endothelin-1 on preeclampsia-like conditions in mice. Hypertension. 2018;71(5):894–903. doi: 10.1161/ HYPERTENSIONAHA.117.10849.
Leung JWC, Wong WT, Koon HW, Mo FM, Tam S, Huang Y, et al. Transgenic mice over-expressing et-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. PLoS One. 2011;6(11). doi: 10.1371/journal. pone.0026994
Shu W, Li H, Gong H, Zhang M, Niu X, Ma Y, et al. Evaluation of blood vessel injury, oxidative stress and circulating inflammatory factors in an l-name-induced preeclampsia-like rat model. Exp Ther Med. 2018;16(2):585–94. doi: 10.3892/ etm.2018.6217
Fishel Bartal M, Lindheimer MD, Sibai BM. Proteinuria during pregnancy: definition, pathophysiology, methodology, and clinical significance. Am J Obs Gynecol. 2020;10. doi: 10.1016/j.ajog.2020.08.108.
Zhu H, Zhu W, Hu R, Wang H, Ma D, Li X. The effect of pre-eclampsia-like syndrome induced by L-NAME on learning and memory and hippocampal glucocorticoid receptor expression: a rat model. Hypertens pregnancy. 2017;36(1):36–43. doi: 10.1080/10641955.2016.1228957.
Brownfoot FC, Tong S, Hannan NJ, Binder NK, Walker SP, Cannon P, et al. Effects of Pravastatin on Human Placenta, Endothelium, and Women With Severe Preeclampsia. Hypertension 2015;66(3):687-97; discussion 445. doi: 10.1161/ HYPERTENSIONAHA.115.05445.
Saad AF, Kechichian T, Yin H, Sbrana E, Longo M, Wen M, et al. Effects of pravastatin on angiogenic and placental hypoxic imbalance in a mouse model of preeclampsia. Reprod Sci. 2014;21(1):138–45. doi: 10.1177/1933719113492207.
Zhou J, Xiao D, Hu Y, Wang Z, Paradis A, Mata- Greenwood E, et al. Gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 signaling in pregnant rats. Hypertension. 2013;62(3):599–607. doi: 10.1161/ HYPERTENSIONAHA.113.01449.
Leo MD, Kandasamy K, Subramani J, Tandan SK, Kumar D. Involvement of inducible nitric oxide synthase and dimethyl arginine dimethylaminohydrolase in Nω-Nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Cardiovasc Pathol [Internet]. 2015;24(1):49–55. doi:10.1016/j.carpath.2014.09.002
Khoubnasab Jafari M, Ansarin K, Jouyban A. Comments on “use of malondialdehyde as a biomarker for assesing oxidative stress in different disease pathologies: A review.” Iran J Public Health. 2015;44(5):714–5.
Chamy Picó VM, Lepe J, Catalán Á, Retamal D, Escobar JA, Madrid EM. Oxidative stress is closely related to clinical severity of pre-eclampsia. Biol Res. 2006;39(2):229–36. doi: 10.4067/s0716- 97602006000200005.
Gajzlerska-Majewska W, Bomba-Opon DA, Wielgos M. Is pravastatin a milestone in the prevention and treatment of preeclampsia? J Perinat Med. 2018;46(8):825–31. doi: 10.1515/jpm-2017- 0109.
Wassmann S, Faul A, Hennen B, Scheller B, Böhm M, Nickenig G. Rapid effect of 3-hydroxy- 3-methylglutaryl coenzyme a reductase inhibition on coronary endothelial function. Circ Res. 2003;93(9):e98–103. doi: 10.1161/01. RES.0000099503.13312.7B.
An Y, Xin H, Yan W, Zhou X. Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice. Exp Toxicol Pathol. 2011;63(3):215–9. doi: 10.1016/j.etp.2009.12.002
de Alwis N, Beard S, Mangwiro YT, Binder NK, Kaitu’u-Lino TJ, Brownfoot FC, et al. Pravastatin as the statin of choice for reducing pre-eclampsia- associated endothelial dysfunction. Pregnancy Hypertens [Internet]. 2020;20(January):83–91. doi:10.1016/j.preghy.2020.03.004