Veena C K, Josephine A, Preetha S P, Varalakshmi P
Department of Medical Biochemistry, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Hum Exp Toxicol. 2007 Dec;26(12):923-32. doi: 10.1177/0960327107087792.
Kidney stones are known to haunt humanity for centuries and increase in oxalate is a predominant risk factor for stone formation. The present study was initiated with a notion to study the oxidative and nitrosative stress on erythrocytes under oxalate stress and the putative role of sulphated polysaccharides. Hyperoxaluria was induced in two groups by the administration of 0.75% ethylene glycol in drinking water for 28 days and one of them was treated with sulphated polysaccharides from Fucus vesiculosus from the 8th day to the end of the experimental period of 28 days at a dose of 5 mg/kg body weight subcutaneously. Control and drug control (sulphated polysaccharides alone) were also included in the study. Glycolic and glyoxylic acid levels of urine were analyzed as an index of hyperoxaluria. The plasma enzymic markers of cellular integrity, redox status of red blood cells, osmotic fragility, and (14)C-oxalate binding were investigated. Urine and plasma nitric oxide metabolites, expression of inducible nitric oxide synthase protein, and mRNA were assessed in kidney to evaluate the nitrosative stress. Increased levels of glycolic and glyoxylic acid in urine indicated the prevalence of hyperoxaluria in ethylene glycol-administered groups. Plasma aspartate and alanine transaminase were not altered, but alkaline phosphatase and lactate dehydrogenase of hyperoxaluric group were increased indicating tissue damage. Activities of antioxidant enzymes were decreased, whereas erythrocyte membrane lipid peroxidation was increased in hyperoxaluric rats. Moreover, an altered fragility with an increase in oxalate binding activity was observed in hyperoxaluric group. Increase in nitric oxide metabolites levels in urine and plasma along with an increase in expression of inducible nitric oxide synthase protein and mRNA in kidney were observed in hyperoxaluric rats. Administration of sulphated polysaccharides to hyperoxaluric rats averted the abnormal increase in urinary glycolic and glyoxylic acid levels and enzyme activities, decreased lipid peroxidation, and increased the activities of antioxidant enzymes. Furthermore, increased nitrosative stress accompanying hyperoxaluria was also normalized on sulphated polysaccharides treatment. To conclude, sulphated polysaccharide administration was able to maintain the integrity of erythrocyte membrane and decrease the damage to erythrocytes in hyperoxaluria.
肾结石困扰人类已有数百年之久,而草酸盐增加是结石形成的主要风险因素。本研究旨在探讨草酸盐应激下红细胞的氧化应激和亚硝化应激以及硫酸化多糖的假定作用。通过在饮用水中给予0.75%乙二醇28天,诱导两组大鼠出现高草酸尿症,其中一组从第8天至实验期28天结束,以5mg/kg体重的剂量皮下注射来自墨角藻的硫酸化多糖进行治疗。研究中还包括对照组和药物对照组(仅硫酸化多糖)。分析尿中乙醇酸和乙醛酸水平作为高草酸尿症的指标。研究了细胞完整性的血浆酶标志物、红细胞的氧化还原状态、渗透脆性以及(14)C-草酸盐结合情况。评估了尿和血浆中的一氧化氮代谢产物、诱导型一氧化氮合酶蛋白和mRNA的表达,以评估亚硝化应激。尿中乙醇酸和乙醛酸水平升高表明给予乙二醇的组中存在高草酸尿症。血浆天冬氨酸转氨酶和丙氨酸转氨酶未改变,但高草酸尿症组的碱性磷酸酶和乳酸脱氢酶升高,表明组织损伤。高草酸尿症大鼠中抗氧化酶活性降低,而红细胞膜脂质过氧化增加。此外,在高草酸尿症组中观察到脆性改变以及草酸盐结合活性增加。高草酸尿症大鼠尿和血浆中一氧化氮代谢产物水平升高,同时肾脏中诱导型一氧化氮合酶蛋白和mRNA表达增加。给高草酸尿症大鼠施用硫酸化多糖可避免尿中乙醇酸和乙醛酸水平以及酶活性的异常升高,降低脂质过氧化,并增加抗氧化酶活性。此外,高草酸尿症伴随的亚硝化应激增加在硫酸化多糖治疗后也恢复正常。总之,施用硫酸化多糖能够维持红细胞膜的完整性,并减少高草酸尿症中红细胞的损伤。