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高剂量硼对大鼠肾结石和氧化应激没有保护作用。

High Doses of Boron Have No Protective Effect Against Nephrolithiasis or Oxidative Stress in a Rat Model.

机构信息

Department of Pediatrics, University of Health Sciences, Kayseri Training and Research Hospital, Kayseri, Turkey.

Department of Pharmacology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.

出版信息

Biol Trace Elem Res. 2018 Nov;186(1):218-225. doi: 10.1007/s12011-018-1294-1. Epub 2018 Mar 8.

Abstract

Boron plays roles in the metabolism of calcium, vitamin D, steroid hormones, healthy bone development, and maintenance of cell membranes. The biological effects of boron are dose-dependent but follow a U-shaped pattern, rendering it important to define the active range. The studies of Bahadoran et al. on rats and Naghii et al. on humans showed that low doses of boron (3 and 10 mg/day) prevented kidney stone formation. The aim of this study was to determine whether high doses of boron have an anti-urolithiatic or antioxidant effect on nephrolithiasis in an experimental rat model. The study was conducted on 50 adult male Wistar rats randomized to five groups. Nephrolithiasis was induced with water containing 0.75% ethylene glycol (EG) and 2% ammonium chloride (AC). This treatment was given to animals in all groups for 10 days, except the positive and negative controls. Simultaneously, groups 2, 3, and 4 were given boric acid via gavage at doses of 25, 50, and 100 mg/kg/day (equivalent to 4/8/16 mg boron respectively) as the source of boron. Animals in the negative and positive control groups were given 6 μL/g distilled water without boric acid. At day 10, intra-cardiac blood samples were drawn from all animals. The right and left kidneys were removed for biochemical and histopathological examinations, respectively. The groups were compared with respect to serum urea, creatinine, calcium, phosphorous, total antioxidant status (TAS), total oxidant status (TOS), serum paraoxonase (PON1) activity, tissue calcium and oxalate levels, and stone burden as determined by histopathological examination. Serum urea and creatinine levels were significantly higher (p < 0.001 and p < 0.05, respectively), while serum calcium and phosphorous levels were significantly lower (p < 0.001 and p < 0.001, respectively), in animals given EG/AC compared to negative controls. No significant differences were detected in serum calcium, phosphorous, urea, or creatinine levels between animals treated with boron and positive controls (p > 0.05). Serum PON1 activity was significantly lower in animals given EG/AC than in negative controls (p < 0.001), while no significant difference in serum PON1 level was detected between rats treated with boron and positive controls. No significant differences were detected in vitamin D, TAS, TOS, tissue calcium, or tissue oxalate levels among groups. No stone formation was detected on histopathological examination in negative controls. No significant differences were found in stone formation between rats treated with boron and positive controls. Based on this study, high doses of boron had no protective effect against nephrolithiasis and oxidative stress.

摘要

硼在钙、维生素 D、类固醇激素、健康骨骼发育和维持细胞膜的新陈代谢中发挥作用。硼的生物学效应与剂量有关,但呈 U 形模式,因此确定有效范围很重要。Bahadoran 等人在大鼠和 Naghii 等人在人体上的研究表明,低剂量的硼(3 和 10mg/天)可预防肾结石形成。本研究旨在确定高剂量硼对实验性大鼠肾结石模型是否具有抗尿石形成或抗氧化作用。该研究共纳入 50 只成年雄性 Wistar 大鼠,随机分为五组。通过给予含 0.75%乙二醇(EG)和 2%氯化铵(AC)的水来诱导肾结石形成。除阳性和阴性对照组外,所有组的动物均接受此治疗 10 天。同时,第 2、3 和 4 组通过灌胃分别给予 25、50 和 100mg/kg/天的硼酸(分别相当于 4/8/16mg 硼)作为硼源。阴性和阳性对照组的动物给予不含硼酸的 6μL/g 蒸馏水。第 10 天,从所有动物抽取心内血样。分别取出右肾和左肾进行生化和组织病理学检查。比较各组血清尿素、肌酐、钙、磷、总抗氧化状态(TAS)、总氧化状态(TOS)、血清对氧磷酶 1(PON1)活性、组织钙和草酸盐水平以及组织病理学检查确定的结石负担。与阴性对照组相比,给予 EG/AC 的动物血清尿素和肌酐水平显著升高(p<0.001 和 p<0.05),而血清钙和磷水平显著降低(p<0.001 和 p<0.001)。与阳性对照组相比,给予硼的动物的血清钙、磷、尿素或肌酐水平无显著差异(p>0.05)。与阴性对照组相比,给予 EG/AC 的动物血清 PON1 活性显著降低(p<0.001),而硼处理的大鼠与阳性对照组之间的血清 PON1 水平无显著差异。各组间维生素 D、TAS、TOS、组织钙或组织草酸盐水平无显著差异。阴性对照组的组织病理学检查未见结石形成。硼处理的大鼠与阳性对照组之间的结石形成无显著差异。基于本研究,高剂量硼对肾结石和氧化应激没有保护作用。

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