ABSTRACT MUHAMAD FIRDAUS. Antioxidant activity of brown algae (Sargassum echinocarpum) as preventive on dysfunction of endothelium cell in aorta of diabetes mellitus rats. Under supervision of MADE ASTAWAN as chairman, DEDDY MUCHTADI, TUTIK WRESDIYATI, SARWONO WASPADJI, and SETYAWATI S. KARYONO, as member committee. Diabetes mellitus may cause oxidative stress. Chronic oxidative stress initiates the dysfunction of endothelium cell. Polyphenols are believed to have ability to prevent the dysfunction of endothelium cell. Marine brown algae contain polyphenol which is probably has good antioxidant activity. The aims of this study were to obtain the antioxidant activity and structure of phlorotannin, the lethal dose, the anti oxidative stress, and the anti endothelium cell dysfunction of Sargassum echinocarpum extract. The Sargassum echinocarpum was collected in April 2008 from the coastline of Talango island in Sumenep District of East Java, Indonesia and authenticated by the botanist, Research Centre of Oceanography, Indonesian Institute of Sciences. The antioxidant activity was assayed with DPPH radicals, the structure elucidation was assessed with spectroscopic methods, the lethal dose was investigated on mice, and the anti oxidative stress and the anti endothelium cell dysfunction were evaluated in diabetic rats. The experimental animals were divided into 5 groups, i.e.: (1) normal, (2) diabetic treated with 0, (3) 150, (4) 300, and (5) 450 mg/kg body weight of Sargassum echinocarpum extract, respectively. Extracts were administered by oral gavages for 12 weeks. Diabetes was induced by single administration of streptozotocin (45 mg/kg, i.p.). Diabetes was confirmed ten days later in streptozotocin induced animals with blood glucose levels > 200 mg/dL. After the treatment period, the blood serum acquired was used for antioxidant enzymes assays while the thoracic aorta was used for vasodilatation assay. The result showed that the phlorotannin content of Sargassum echinocarpum extract was 4.25 - 12.16 equivalent of mg phloroglucinol/g extract. The strongest antioxidant activity obtained from the methanol extract of Sargassum echinocarpum, i.e. 67.77 %. The methanol extract of Sargassum echinocarpum contained phloroglucinol and bifuhalol. The methanol extract of Sargassum echinocarpum was relatively non-toxic. The mice treated with 1250 mg/kg or more methanol extract of Sargassum echinocarpum showed inhibition of body weight and necrosis on hepatocyte and tubules of kidney. It was affected by inhibition activity of gastrointestinal enzymes and initiation lipid peroxidation. The diabetic rats revealed the oxidative stress; meanwhile, the diabetic rats treated with 450 mg/kg extract showed the mild oxidative stress. It was caused by free radical scavenging and induction of antioxidant defense activity by extract. The diabetic rats exhibited the endothelial dysfunction; meanwhile, the diabetic rats treated with 450 mg/kg extract showed the mild endothelial dysfunction. It appeared that Sargassum echinocarpum extract has the capability to preserve bioavailability of nitric oxide and protect the muscarinic receptor and endothelium cell against free radical damage. Keywords: Antioxidant, diabetes mellitus, endothelium cell dysfunction, rat, Sargassum echinocarpum
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