MANAGEMENT OF INDUCED PREECLAMPSIA IN ANIMAL MODEL

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ABSTRACT

Preeclampsia is a syndrome defined as elevated blood pressure of ≥140/90 mmHg, measured on at least two occasions separated by 6 hours after the twentieth week of pregnancy. It occurs in a previously normotensive woman and is accompanied by significant proteinuria (300mg/L or 500mg/24 hours) in the absence of a Urinary Tract Infection. It has remained a significant public health threat in both developed and developing countries contributing to maternal and perinatal morbidity and mortality globally. Although orthodox medical care involving hypertension medication may enhance maternal outcomes, they have the potential to be harmful to the foetus. Perhaps, the use of plant extracts may serve as an alternative. The focus of this research therefore was to investigate possible treatment of preeclampsia in Wistar Rat Models using selected local plant extracts. An ethnobotanical (reconnaissance) survey was conducted within Benin City with a view to determining most available plants for the management of hypertension, kidney anomalies as well as pregnancy-related illness. This would form the basis for plant selection for use in the study. Fifty (50) individuals were interviewed within 5 Local Government Areas in Benin City (Ikpoba Okha, Oredo, Egor, Ovia North East and Uhunmwonde). Following standard procedure, Relative Frequency of Citation was calculated to show the importance of each plant species for which information was sought during the survey and then the three most commonly cited plants (Jatropha curcas, Alchornea cordifolia, and Secamone afzelii) were selected for use. Methanolic extracts of the leaves of these plants were thereafter prepared following standard procedure. The study employed age-matched female Wistar rats which were housed in metabolic cages, and given unrestricted access to a standard diet as well as ad libitum tap water (pH range 6.8 – 7.2). With the exception of the control group, the animals were then given 10, 100, 500, 1000, and 5000 mg/kg body weight of the extracts orally, on a daily basis for 15 days, while morbidity and mortality were measured on Days 1, 3, 6, 9, 12, and 15 respectively for acute toxicity. The Adriamycin Model was used to induce preeclampsia. The preeclamptic animals were then administered different doses (50, 100, and 200 mg/kg) of the plant extracts daily until were ready to be delivered of their pops. Determination of blood pressure of the Wistar rat was by the non invasive method; whereas determination of proteinuria was by dipstick method. ECG was conducted following standard protocol. After animals were humanely sacrificed, blood was collected for biochemical, haematological, and antioxidant studies; while the organs were harvested for histological evaluation. Parameters evaluated for teratogenicity included morphometry of placenta, uterus, foetus. Data collected were analyzed using SPSS version 20 and GraphPad Prism version 5; with result means separated using Least Significant Differences. Results showed that when the methanolic extracts of the test plants were administered to the Wistar rats for the first 15 days, no mortalility was recorded for the highest concentration (5000 mg/kg) indicating negative acute toxicity. This study has shown that J. curcas, A. cordifolia and S. afzelii can reduce blood pressure and proteinuria, both of which are symptoms of preeclampsia. Blood pressure during 3rd trimester in the preeclamptic Wistar rats was 177/121 mmHg, but was significantly reduced to 119/86 mmHg upon administration of methanolic extracts of J. curcas. Results also showed that the incidence of preeclampsia had no significant effects on the heart presentations as shown in the ECG and histology reports. Proteinuria was negative in the control group as expected. However, during 3rd trimester, proteinuria was 3+ in the preeclamptic group but significantly reduced to 1+ at postpartum. Similarly, there was at least 33% reduction in level of proteinuria upon administration of plant extracts during the 3rd trimester. Administration of 50mg/kg of methanolic extracts of J. curcas reduced proteinuria by over 60% in the preeclamptic group. Results showed improvements in haematological parameters in the preeclamptic groups treated with all 3 plant extracts. The methanolic extracts of J. curcas, A. cordifolia, and S. afzelii were not acutely harmful to pregnant Wistar rats at the levels used in this investigation; however, extracts of A. cordifolia were teratogenic. At doses more than 50mg/kg of A. cordifolia extracts, pregnant Wistar rats produced 7 dead fetuses out of 9 implantations; the live fetuses were all deformed. Other deformities recorded were morphometric variations in the placenta sizes, weights, and volumes. Whereas extracts of J. curcas showed better result outcomes, Alchornea cordifolia showed significant teratogenic toxicity. Therefore its use is contraindicated during pregnancies.

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