Pengaruh Pemberian Extra Virgin Olive Oil Terhadap Aktivitas Superoxide Dismutase (Sod) Dan Kadar Vascular Endothelial Growth Factor (Vegf) Tikus Rattus Norvegicus Bunting Model Preeklamsia

Lovita, Agnestia Naning Dian (2019) Pengaruh Pemberian Extra Virgin Olive Oil Terhadap Aktivitas Superoxide Dismutase (Sod) Dan Kadar Vascular Endothelial Growth Factor (Vegf) Tikus Rattus Norvegicus Bunting Model Preeklamsia. Magister thesis, Universitas Brawijaya.

Abstract

Preeklamsia adalah penyakit khusus dalam kehamilan yang melibatkan berbagai patofisiologis termasuk stress oksidatif dan angiogenesis. Gangguan remodeling arteri spiralis menyebabkan aliran darah arteri bersifat intermiten sehingga menghasilkan periode iskemia / reperfusi dan menimbulkan hipoksia. Hipoksia plasenta mengarah ke stress oksidatif yang ditandai dengan peningkatan Malondialdehyde (MDA) dan penurunan aktivitas antioksidan endogen seperti Superoxide Dismutase (SOD). Faktor lain yang terlibat dalam patofisiologi preeklamsia adalah faktor angiogenesis seperti Vascular Endhotelial Growth Factor (VEGF). Kondisi hipoksia yang terjadi pada preeklamsia mengakibatkan Soluble Fms-like Tyrosine Kinase 1 (sFlt-1) sebagai faktor antiangiogenik diproduksi dalam konsentrasi yang tinggi. sFlt-1 mampu berikatan dengan VEGF mengganggu proses angiogenesis dengan menurunkan bioavailability VEGF terhadap reseptornya. Hal ini menyebabkan penurunan kadar VEGF bebas pada preeklamsia. Gangguan keseimbangan faktor pro-angiogenik dan anti-angiogenik ini mengakibatkan disfungsi sistemik vaskuler yang bertanggung jawab atas manifestasi klinis yang muncul pada preeklamsia. Extra Virgin Olive Oil (EVOO) memiliki peran potensial sebagai antioksidan dan memodulasi angiogenesis untuk mencegah dampak buruk preeklamsia. polifenol EVOO menurunkan produksi ROS, berperan penting sebagai scavenger radikal bebas, serta meningkatkan total plasma antioxidant activity termasuk SOD. Selain itu kandungan polifenol dalam EVOO juga mempengaruhi angiogenesis melalui Nuclear Factor Erythroid 2-related Factor-2 (Nrf2) yang berhubungan dengan peningkatan VEGF. Penelitian ini bertujuan mengetahui pengaruh EVOO untuk meningkatkan aktivitas SOD dan kadar VEGF pada tikus bunting model preeklamsia. Desain penelitian adalah true experiment randomized post test only control group design sebanyak 20 tikus yang dibagi dalam 5 kelompok perlakuan : kontrol negatif, kontrol positif (tikus bunting model preeklamsia), tikus bunting model preeklamsia yang diberi EVOO dosis I 0.5 mL/hari, EVOO dosis II 1 mL/hari, EVOO dosis III 2 mL/hari. Pemberian EVOO per oral menggunakan sonde dilakukan mulai hari pertama sampai 18 kebuntingan, tikus model preeklamsia dibuat dengan melakukan injeksi L-NAME 125 mg/kgBB intraperitoneal mulai hari ke – 13 sampai 18 kebuntingan. Pengukuran tekanan darah dan proteinuria dilakukan pada hari ke – 12, 15 dan 19 kebuntingan. Pembedahan dilakukan pada hari ke – 19 kebuntingan lalu plasenta dan plasma maternal diambil untuk menentukan aktivitas SOD dan kadar VEGF. Hasil penelitian menunjukkan peningkatan aktivitas SOD yang signifikan antara kelompok kontrol positif dan kontrol negatif (p=0.049) dan penurunan kadar VEGF yang signifikan antara kelompok kontrol positif dan kontrol negatif (p=0.009). Setelah pemberian EVOO, aktivitas SOD pada kelompok dosis I menurun dibandingkan kontrol positif. Seiring dengan penambahan dosis EVOO, aktivitas SOD meningkat pada dosis II dan III. Sementara itu, kadar VEGF meningkat di kelompok dosis I dan II namun menurun pada dosis III. Aktivitas SOD berbeda signifikan antara kelompok kontrol positif dan dosis 1 (p=0.008), namun kadar VEGF tidak ada yang berbeda signifikan antara kelompok kontrol positif dengan ketiga dosis (p=0.601; p=0.297; p=0.805). Pemberian EVOO per oral mempengaruhi peningkatan aktivitas SOD dan kadar VEGF tikus Rattus norvegicus bunting model preeklamsia secara signifikan. EVOO terbukti sebagai antioksidan potent dan memodulasi angiogenesis pada tikus bunting model preeklamsia melalui peningkatan aktivitas SOD dan kadar VEGF

English Abstract

Preeclampsia is a special disease in pregnancy that involve various pathophysiologies including oxidative stress and angiogenesis. Disruption of spiral artery remodeling causes intermittent arterial blood flow resulting period of ischemia / reperfusion lead to hypoxia. Placental hypoxia causes oxidative stress characterized by increase Malondialdehyde (MDA) and decrease endogenous antioxidant activity such as Superoxide Dismutase (SOD). Another factor involved in pathophysiology of preeclampsia is angiogenesis such as Vascular Endhotelial Growth Factor (VEGF). Hypoxic condition in preeclampsia cause Soluble Fms-like Tyrosine Kinase 1 (sFlt-1) as an antiangiogenic factor produced in high concentrations. sFlt-1 icapable of binding to VEGF to interfere with the process of angiogenesis by reducing the bioavailability of VEGF to its receptors. This causes a decrease in free VEGF levels in preeclampsia. This balance disorder of pro- angiogenic and anti-angiogenic factors resulting vascular systemic dysfunction responsible for clinical manifestations that appear in preeclampsia. Extra Virgin Olive Oil (EVOO) has potential role as antioxidant and modulate angiogenesis to prevent adverse effects of preeclampsia. EVOO polyphenols reduce ROS production, play an important role as a free radical scavenger and increase total plasma antioxidant activity including SOD. Polyphenol in EVOO also affect angiogenesis through Nuclear Factor Erythroid 2-related Factor-2 (Nrf2) which associated with increase VEGF. This study aimed to determine effect of EVOO to increase SOD activity and VEGF levels in preeclampsia pregnant rat model. This study used true experiment randomized post-test only control group study and as many as 20 rats divided into 5 groups: negative control, positive control (preeclampsia rat model), preeclampsia rat model were given EVOO 0.5 mL / day dose I, EVOO 1 mL / day dose II, EVOO 2 mL / day dose III. Administration of EVOO using sonde were carried out from the first to the 18th day of pregnancy, preeclampsia rat model were made by injecting L-NAME 125 mg/kgBW intraperitoneal from the 13th to 18th day of pregnancy. Blood pressure and proteinuria measurements were carried out on 12th, 15th and 19th day of pregnancy. Rats were sacrificed on 19th day of pregnancy then placentas and maternal plasma were taken to determine SOD activity and VEGF levels. Result of this study showed significant increase in SOD activity between the positive control and negative controls (p = 0.049) and significant decrease in VEGF levels between positive control and negative controls (p = 0.009). After the administration of EVOO, SOD activity in the dose I group decreased compared to positive controls. SOD activity increased in doses II and III in accordance with addition EVOO doses. Meanwhile, VEGF levels increased in the dose I and II groups but decreased in dose III. SOD activity was significantly different between positive control and dose 1 (p = 0.008), but there were no significant difference of VEGF level between positive control and all doses groups (p = 0.601; p = 0.297; p = 0.805). Oral administration of EVOO affect enhancement of SOD activity and VEGF levels in preeclampsia pregnant rat model significantly. EVOO has been shown to be a potent antioxidant and modulates angiogenesis in preeclampsia pregnant rat model through increased SOD activity and VEGF levels.

Other obstract

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Item Type:	Thesis (Magister)
Identification Number:	TES/615.323 87/LOV/p/2019/041905121
Uncontrolled Keywords:	Extra Virgin Olive Oil, Superoxide Dismutase, Vascular Endothelial Growth Factor
Subjects:	600 Technology (Applied sciences) > 615 Pharmacology and therapeutics > 615.3 Organics drugs > 615.32 Drugs derived from plants and mikroorganisms > 615.323 87 Drugs derived from olive oil
Divisions:	S2/S3 > Magister Kebidanan, Fakultas Kedokteran
Depositing User:	Endang Susworini
Date Deposited:	18 Jul 2022 08:10
Last Modified:	18 Jul 2022 08:10
URI:	http://repository.ub.ac.id/id/eprint/192225

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