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在饮用了来自斯里兰卡中北部省(NCP)慢性肾脏病(CKDu)高发病区和低发病区的开水及生水后,Wistar大鼠的生化和组织病理学变化,及其与低发病区科伦坡的比较

Biochemical and histopathological changes in Wistar rats after consumption of boiled and un-boiled water from high and low disease prevalent areas for chronic kidney disease of unknown etiology (CKDu) in north Central Province (NCP) and its comparison with low disease prevalent Colombo, Sri Lanka.

作者信息

Thammitiyagodage M G, de Silva N R, Rathnayake C, Karunakaran R, Wgss Kumara, Gunatillka M M, Ekanayaka N, Galhena B P, Thabrew M I

机构信息

Medical Research Institute, Dr. Danister de Silva Mawatha, Colombo 8, Sri Lanka.

Department of Bio Chemistry & Clinical Chemistry, Faculty of Medicine, University of Kelaniya, Thalagolla Road, Ragama, Sri Lanka.

出版信息

BMC Nephrol. 2020 Jan 31;21(1):38. doi: 10.1186/s12882-020-1693-3.

Abstract

BACKGROUND

Chronic Kidney Disease of unknown etiology (CKDu) is prevalent in North Central Province (NCP) of Sri Lanka. Consumption of un-boiled dug well water has been identified as one of the causative factors. This in-vivo study was performed to investigate some of the suspected factors associated with the pathogenesis of CKDu mediated via ground water.

METHOD

Rats were given water, collected from high and low disease prevalent areas from the NCP of Sri Lanka and the results compared with those obtained from previously identified low disease prevalent area; Colombo. Blood Urea Nitrogen, creatinine, urinary microalbumin:creatinine ratio together with ALT and AST levels were analyzed and results were compared using one-way ANOVA and paired t-Test. Histopathology was analyzed using non-parametric method.

RESULTS

Rats that ingested water from New Town Medirigiriya (NTM) from high disease prevalent NCP reported significantly elevated microalbumin:creatinine ratios compared to other water sources after 8 months, whilst boiled water from NTM had been able to significantly reduce it. Histopathological findings after the 14 months experimental period revealed significantly high tubular lesion index in rats that ingested water from NCP compared to Colombo. Rats that ingested water from high disease prevalent Divuldamana (DD) from NCP showed the highest kidney lesion index though the fluoride content was relatively low in this area compared to other water sources from high disease prevalent NCP. Rats that ingested boiled and un-boiled water from NTM also developed severe lesions whilst the group from Colombo reported the lowest. Low disease prevalent area from NCP, Huruluwewa (HW) also reported elevated liver enzymes and altered renal histopathology. Association of Na:Ca ratio in the disease progression was not reflected by the current study. Compared to Colombo, high fluoride, calcium and sodium contents were observed in water from high disease prevalent areas. All the water samples were negative for heavy metals.

CONCLUSIONS

Though Fluoride is a known kidney toxic agent it cannot be the sole reason for CKDu in NCP, Sri Lanka. Various toxic elements present in NCP water may contribute to different grade of kidney and liver lesions in Wistar rats.

摘要

背景

病因不明的慢性肾脏病(CKDu)在斯里兰卡中北部省(NCP)很普遍。饮用未煮沸的井水已被确定为致病因素之一。本体内研究旨在调查一些与通过地下水介导的CKDu发病机制相关的可疑因素。

方法

给大鼠饮用从斯里兰卡NCP高发病区和低发病区采集的水,并将结果与之前确定的低发病区科伦坡的结果进行比较。分析血尿素氮、肌酐、尿微量白蛋白:肌酐比值以及谷丙转氨酶和谷草转氨酶水平,并使用单因素方差分析和配对t检验比较结果。使用非参数方法分析组织病理学。

结果

与其他水源相比,饮用来自NCP高发病区新城梅迪里吉里亚(NTM)的水的大鼠在8个月后尿微量白蛋白:肌酐比值显著升高,而NTM的开水能够显著降低该比值。14个月实验期后的组织病理学结果显示,与科伦坡相比,饮用NCP水的大鼠肾小管病变指数显著较高。饮用来自NCP高发病区迪武尔达马纳(DD)的水的大鼠肾脏病变指数最高,尽管该地区的氟含量与NCP其他高发病区的水源相比相对较低。饮用NTM煮沸和未煮沸水的大鼠也出现了严重病变,而来自科伦坡的组病变最轻。NCP低发病区胡鲁卢韦瓦(HW)的肝酶也升高,肾脏组织病理学改变。本研究未反映钠:钙比值与疾病进展的关联。与科伦坡相比,高发病区的水中氟、钙和钠含量较高。所有水样重金属均为阴性。

结论

虽然氟是一种已知的肾脏毒性物质,但它不可能是斯里兰卡NCP地区CKDu的唯一原因。NCP水中存在的各种有毒元素可能导致Wistar大鼠不同程度的肾脏和肝脏病变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f42/6995117/1d73359e93da/12882_2020_1693_Fig1_HTML.jpg

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