Quadri J A, Sarwar S, Sinha A, Kalaivani M, Dinda A K, Bagga A, Roy T S, Das T K, Shariff A
1 Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
2 Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Hum Exp Toxicol. 2018 Nov;37(11):1199-1206. doi: 10.1177/0960327118755257. Epub 2018 Feb 14.
The susceptibility of the kidneys to fluoride toxicity can largely be attributed to its anatomy and function. As the filtrate moves along the complex tubular structure of each nephron, it is concentrated in the proximal and distal tubules and collecting duct. It has been frequently observed that the children suffering from renal impairments also have some symptoms of dental and skeletal fluorosis. The findings suggest that fluoride somehow interferes with renal anatomy and physiology, which may lead to renal pathogenesis. The aim of this study was to evaluate the fluoride-associated nephrotoxicity. A total of 156 patients with childhood nephrotic syndrome were screened and it was observed that 32 of them had significantly high levels ( p ≤ 0.05) of fluoride in urine (4.01 ± 1.83 ppm) and serum (0.1 ± 0.013 ppm). On the basis of urinary fluoride concentration, patients were divided into two groups, namely group 1 (G-1) ( n = 32) containing normal urine fluoride (0.61 ± 0.17 ppm) and group 2 (G-2) ( n = 32) having high urine fluoride concentration (4.01 ± 1.83 ppm). Age-matched healthy subjects ( n = 33) having normal levels of urinary fluoride (0.56 ± 0.15 ppm) were included in the study as control (group 0 (G-0)). Kidney biopsies were taken from G-1 and G-2 only, who were subjected to ultrastructural (transmission electron microscopy) and apoptotic (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling) analysis. Various subcellular ultrastructural changes including nuclear disintegration, chromosome condensation, cytoplasmic ground substance lysis, and endoplasmic reticulum blebbing were observed. Increased levels of apoptosis were observed in high fluoride group (G-2) compared to normal fluoride group (G-1). Various degrees of fluoride-associated damages to the architecture of tubular epithelia, such as cell swelling and lysis, cytoplasmic vacuolation, nuclear condensation, apoptosis, and necrosis, were observed.
肾脏对氟中毒的易感性很大程度上可归因于其解剖结构和功能。当滤液沿着每个肾单位复杂的管状结构移动时，它在近端和远端小管以及集合管中被浓缩。人们经常观察到，患有肾功能损害的儿童也有一些牙齿和骨骼氟中毒的症状。这些发现表明，氟以某种方式干扰了肾脏的解剖结构和生理功能，这可能导致肾脏发病机制。本研究的目的是评估与氟相关的肾毒性。总共筛选了156例儿童肾病综合征患者，观察到其中32例尿液（4.01±1.83 ppm）和血清（0.1±0.013 ppm）中的氟含量显著升高（p≤0.05）。根据尿氟浓度，将患者分为两组，即第1组（G-1）（n = 32），尿氟正常（0.61±0.17 ppm），第2组（G-2）（n = 32），尿氟浓度高（4.01±1.83 ppm）。将年龄匹配、尿氟水平正常（0.56±0.15 ppm）的健康受试者（n = 33）纳入研究作为对照（第0组（G-0））。仅从G-1和G-2组进行肾活检，对其进行超微结构（透射电子显微镜）和凋亡（末端脱氧核苷酸转移酶脱氧尿苷三磷酸缺口末端标记）分析。观察到各种亚细胞超微结构变化，包括核解体、染色体浓缩、细胞质基质溶解和内质网泡状化。与正常氟组（G-1）相比，高氟组（G-2）观察到凋亡水平增加。观察到不同程度的与氟相关的肾小管上皮结构损伤，如细胞肿胀和溶解、细胞质空泡化、核浓缩、凋亡和坏死。
