Effect of D-003, a mixture of high molecular weight primary acids from sugar cane wax, on paracetamol-induced liver damage in rats.

S Mendoza, M Noa, R Mas, N Mendoza
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Abstract

D-003 is a mixture of very high molecular weight aliphatic primary acids purified from sugar cane (Saccharum officinarum, L) wax, in which the most abundant component is octacosanoic acid. Experimental studies have shown that D-003 not only shows cholesterol-lowering and antiplatelet effects, but also offers strong protection against plasma lipoprotein oxidation. Previous studies demonstrated that D-003 protected against the histological changes characteristic of Cl4C-induced hepatic injury in rats. The aim of the present study was to investigate the effects of D-003 in acute hepatotoxicity induced by paracetamol in rats. Male Sprague Dawley rats were randomly distributed in two experimental series of three experimental groups as follows: group 1--positive control rats (paracetamol-treated); groups 2 and 3--rats with liver damage induced by paracetamol and treated with D-003 at 5 and 25 mg/kg, respectively, and which also received paracetamol to induce liver injury. In experimental series 1, animals received paracetamol orally (600 mg/kg). In series 2, paracetamol was administered through the intraperitoneal route (200 mg/kg). Eighteen hours after paracetamol dosing, rats were anesthetized with ether and livers were removed for histopathological studies. In the two experimental series, D-003 at 5 and 25 mg/kg significantly (p < 0.01) decreased the percentage of turgent cells and hepatocytes with necrosis and increased the percentage of normal hepatocytes with respect to positive controls in a dose-dependent manner. Necrotic areas and inflammatory infiltrates were observed in the liver of nine out of ten (90%) positive controls. In turn, D-003 dramatically reduced both necrotic areas and inflammatory infiltrate and was present in only one out of ten (10%) animals treated in the two experimental series. No histological alterations in liver sections of negative controls were found. D-003 protected against the histological changes characteristic of paracetamol-induced hepatic injury in rats, in which the process of lipid peroxidation plays a major role. The relationship between this protective action of D-003 in this experimental model and its antioxidant effects needs to be further investigated before definitive conclusions are drawn.

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从甘蔗蜡中提取的高分子量原酸混合物D-003对扑热息痛引起的大鼠肝损伤的影响。
D-003是从甘蔗(Saccharum officinarum, L)蜡中纯化的非常高分子量的脂肪族初级酸的混合物,其中最丰富的成分是八碳酸。实验研究表明,D-003不仅具有降胆固醇和抗血小板作用,而且对血浆脂蛋白氧化具有较强的保护作用。既往研究表明,D-003对cl4c致大鼠肝损伤的组织学改变具有保护作用。本研究旨在探讨D-003对扑热息痛致大鼠急性肝毒性的影响。雄性Sprague Dawley大鼠随机分为两个实验系列,分为三个实验组:1组为阳性对照大鼠(扑热息痛处理);2、3组:对乙酰氨基酚肝损伤大鼠,分别给予5、25 mg/kg D-003治疗,同时给予对乙酰氨基酚肝损伤治疗。在实验系列1中,动物口服扑热息痛(600 mg/kg)。在系列2中,扑热息痛通过腹腔给药(200mg /kg)。扑热息痛给药18小时后,用乙醚麻醉大鼠,取肝进行组织病理学研究。在两个实验系列中,与阳性对照相比,5和25 mg/kg剂量的D-003显著(p < 0.01)降低了急性细胞和坏死肝细胞的百分比,并增加了正常肝细胞的百分比,且呈剂量依赖性。10例阳性对照中有9例(90%)肝脏出现坏死区和炎症浸润。反过来,D-003显著减少了坏死区域和炎症浸润,在两个实验系列中,只有十分之一(10%)的动物出现了D-003。阴性对照组肝脏切片未见组织学改变。D-003对扑热息痛引起的大鼠肝损伤的组织学变化具有保护作用,其中脂质过氧化过程起主要作用。该实验模型中D-003的这种保护作用与其抗氧化作用之间的关系需要进一步研究才能得出明确的结论。
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