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Title:	Kajian toksisiti ekstrak akueus daun piper sarmentosum dan kesan antihipertensinya terhadap tikus
Authors:	Maizura Mohd Zainudin (P51901)
Supervisor:	Zaiton Zakaria, Profesor Madya Dr.
Keywords:	Antihipertensiya Dissertations, Academic -- Malaysia
Issue Date:	4-Mar-2014
Description:	Piper sarmentosum (PS) mempunyai pelbagai kesan seperti antikanser, antiradang, hipoglisemik, antikulat, antiaterosklerosis dan antioksidan. Walaupun PS digunakan dengan meluas, namun masih tiada kajian kesan toksik menyeluruh mengenainya dilaporkan. Tambahan pula kajian toksisiti menyeluruh adalah satu keperluan untuk memulakan kajian terhadap manusia. Menurut Kementerian Kesihatan Malaysia, insiden hipertensi semakin meningkat dan hanya 26% daripada pesakit yang dirawat berjaya megawal tekanan darah dan majoritinya menggunakan perubatan herba walaupun kekurangan bukti saintifik yang menyokong hal ini. Oleh itu, kajian ini bertujuan untuk menentukan kesan toksik ekstrak akueus daun PS (EAPS) dan dos selamat penggunaannya pada manusia. Selain itu, kajian ini bertujuan menentukan kesan KadukmyTM terhadap tekanan darah, paras NO, petanda tekanan oksidatif dan aras kolesterol tikus hipertensi spontan (SHR). Ekstrak diberikan kepada lima ekor tikus betina dengan dos tinggi tunggal 5000 mg/kg melalui gavaj oral dalam kajian toksisiti akut. Seterusnya, dalam kajian subakut, ekstrak diberikan kepada enam ekor tikus jantan dan betina dalam dos harian 50, 300 dan 2000 mg/kg, dan air bergaram bagi kawalan selama 28 hari berturut-turut. Untuk kajian subkronik, ekstrak diberikan kepada sepuluh ekor tikus jantan dan betina dalam dos harian 50, 500 dan 2000 mg/kg dan enam ekor tikus jantan dan betina untuk kumpulan kawalan dan satelit selama 90 hari berturut-turut. Pemerhatian umum, kematian, parameter hematologi, biokimia dan histologi ditentukan sebelum dan selepas rawatan selama 14 hari untuk kajian akut, 28 hari untuk subakut dan 90 hari untuk subkronik dengan 14 hari lanjutan bagi kumpulan satelit. Dalam kajian antihipertensi, tikus dibahagikan kepada tiga kumpulan rawatan dan dua kumpulan kawalan. Ujian darah dilakukan sebelum dan selepas rawatan. Tikus dirawat selama 28 hari berturut-turut dan tekanan darah ditentukan pada setiap minggu. Median dosis maut EAPS ditentukan melebihi 5g/kg berat tikus. Tiada morbiditi dan kematian direkodkan dalam kajian toksisiti akut, subakut dan subkronik. Profil hematologi menunjukkan tahap konsisten hemoglobin dan pengurangan sel darah putih. Profil biokimia dan histologi ginjal dan hepar menunjukkan tiada perubahan ketara dan data berada pada julat normal kecuali kejadian hiperkalemia dan keradangan ringan pada ginjal kumpulan rawatan dos 500 dan 2000 mg/kg dalam kajian subkronik. Untuk kajian antihipertensi, KadukmyTM dapat mengurangkan tekanan darah sistolik, diastolik dan min tekanan arteri (p<0.05), meningkatkan NO (p<0.05), mengurangkan malondialdehid (p<0.05) dan mengurangkan kolesterol jumlah dengan ketara dalam kumpulan rawatan KadukmyTM. Keputusan ini mencadangkan bahawa pendedahan akut, subakut dan subkronik dos tinggi EAPS tidak menunjukkan kesan toksik nyata khususnya dalam darah, ginjal dan hepar tikus tetapi memerlukan pemantauan fungsi buah pinggang. KadukmyTM menunjukkan aktiviti antioksidan yang mengurangkan tekanan oksidatif dan aras kolesterol justeru meningkatkan pengeluaran NO dan mengurangkan tekanan darah pada tikus SHR.,Piper sarmentosum (PS) has a variety of effects such as anticancer, anti-inflammatory, hypoglycemic, antifungal, antiatherosclerosis and antioxidant. Although PS is widely used, there is no comprehensive study about its toxic effects reported. In addition, to begin the studies on human, a comprehensive toxicity study is a necessity. According to the Ministry of Health of Malaysia, the incidence of hypertension is increasing. Only 26% of the patients treated achieved controlled blood pressure and majority resorted to herbal medicine despite the lack of scientific evidence to support this. Therefore, the aim of this study is to determine the toxic effect of aqueous extract of PS leaves (EAPS) and safe doses of its use in human. In addition, this study aims to determine the effect of KadukmyTM on blood pressure, NO level, oxidative stress marker and cholesterol level of spontaneously hypertensive rats (SHR). The extract was given to five female rats in a single high dose 5000 mg/kg via oral gavage in the acute toxicity study. Next, in the subacute study, EAPS was given to six male and female rats in daily doses of 50, 300 and 2000 mg/kg, and normal saline control for 28 consecutive days. For the subchronic study, the extract was given to ten male and female rats in daily doses of 50, 500 and 2000 mg/kg and six male and female rats for the control and the satellite groups for 90 consecutive days. General observations, mortality, hematological, biochemical and histological parameters were determined before and after treatment for 14 days for acute study, 28 days for the subacute study and 90 days for subchronic study with 14 days extensions for the satellite groups. In the antihypertensive study, rats were divided into three treatment groups and two control groups. Blood tests were done before and after treatment. Rats were treated for 28 consecutive days, and blood pressure were measured weekly. The median lethal dose of EAPS in rats were determined to be more than 5g/kg body weight. No morbidity and mortality were recorded in the acute, subacute and subchronic toxicity study. Haematological profile showed consistent levels of hemoglobin and white blood cell reduction. Biochemical and histological profile of kidney and liver showed no significant changes and the data is within the normal range except for occurrence of hiperkalemia and mild inflammation in the kidney of rats in the treatment groups dose 500 and 2000 mg/kg in the subchronic study. For the antihipertensive study, KadukmyTM significantly reduced the systolic, diastolic and mean arterial pressure (p<0.05), increased NO level (p<0.05), reduced malondialdehyde level (p<0.05) and reduced the cholesterol level in the treatment group. These results suggested that acute, subacute and subchronic exposure of EAPS did not show obvious toxic effects, particularly in blood, kidney and liver of rats but monitoring of kidney function is required. KadukmyTM also exerts its antioxidant activity to reduce oxidative stress and cholesterol level while increasing NO production and reduce blood pressure in SHR.,PhD
Pages:	226
Publisher:	UKM, Kuala Lumpur
Appears in Collections:	Faculty of Medicine / Fakulti Perubatan

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