In vitro and in vivo anti-coagulant activity and toxicological studies of marine sulfated glycosaminoglycans

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• 作者：Fatma Krichen^a ; Zohra Ghlissi^b ; Ikram Ben Amor^c ; Nadhem Sayari^a ; Rim Kallel^d ; Jalel Gargouri^c ; Zouheir Sahnoun^b ; Tahia Boudawara^d ; Ali Bougatef^a ; ^{ali.bougatef79@gmail.com}
• 关键词：Anticoagulant activity ; Fish skins ; Sulfated glycosaminoglycans ; Toxicological studies
• 刊名：Experimental and Toxicologic Pathology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：69
• 期：1
• 页码：45-53
• 全文大小：1629 K
• 卷排序：69

文摘

The present study aimed to characterize and evaluate the in vitro and in vivo anticoagulant activity of sulfated glycosaminoglycans from the skins of smooth hound (SHSG) and grey triggerfish (GTSG). The analysis of SHSG and GTSG with acetate cellulose electrophoresis in Zn-acetate revealed the presence of hyaluronic acid (HA), chondroitin sulfate (CS) and dermatan sulfate (DS). Both glycosaminoglycans were evaluated for their in vitro anticoagulant activities using activated partial thromboplastin time (aPTT), thrombin time (TT) and prothrombine time (PT) tests. SHSG and GTSG and calciparin were tested as in vivo anticoagulants by subcutaneous (s.c) injection to adult female Wistar rats in a concentration of 75 mg/kg of body weight. The administration of SHSG, GTSG and calciparin to rats induced a significant decrease of platelet rates compared to the control. The aPTT assay of SHSG and GTSG was prolonged 1.3 and 1.23-fold respectively compared with the control. Toxicity studies were performed to investigate whether or not SHSG and GTSG can cause pathological changes in the liver, proteins and DNA. The concentration and catalytic activity of liver oxidative stress markers and enzymes, respectively, as well as the observed hepatic morphological changes indicated that calciparin induced hepatic toxicity and oxidative damage in the liver. The higher activity and lower toxicity of SHSG and GTSG recommended these compounds as a better drug candidate than calciparin.