Fluoride-associated ultrastructural changes and apoptosis in human renal tubule: a pilot study

2018 ◽  
Vol 37 (11) ◽  
pp. 1199-1206 ◽  
Author(s):  
JA Quadri ◽  
S Sarwar ◽  
A Sinha ◽  
M Kalaivani ◽  
AK Dinda ◽  
...  

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.

1969 ◽  
Vol 15 (1) ◽  
pp. 128-129 ◽  
Author(s):  
S. K. Maheswaran ◽  
S. P. Frommes ◽  
R. K. Lindorfer

Purified alpha toxin was cytotoxic to rabbit neutrophils as revealed by electron microscopy. Cells treated with alpha toxin showed aggregation of glycogen granules, extensive degranulation, and loss of cytoplasmic ground substance. Vesicles were present within the cytoplasm and outside the cells. The nuclear lobes were round and showed chromatin dissolution. Degranulation of the cell resulted in the formation of vesicles. These ultrastructural changes, except the nuclear changes, were similar to those of leucocytes treated with P-V leucocidin.


Author(s):  
K.R. Porter

Most types of cells are known from their structure and overall form to possess a characteristic organization. In some instances this is evident in the non-random disposition of organelles and such system subunits as cisternae of the endoplasmic reticulum or the Golgi complex. In others it appears in the distribution and orientation of cytoplasmic fibrils. And in yet others the organization finds expression in the non-random distribution and orientation of microtubules, especially as found in highly anisometric cells and cell processes. The impression is unavoidable that in none of these cases is the organization achieved without the involvement of the cytoplasmic ground substance (CGS) or matrix. This impression is based on the fact that a matrix is present and that in all instances these formed structures, whether membranelimited or filamentous, are suspended in it. In some well-known instances, as in arrays of microtubules which make up axonemes and axostyles, the matrix resolves itself into bridges (and spokes) between the microtubules, bridges which are in some cases very regularly disposed and uniform in size (Mcintosh, 1973; Bloodgood and Miller, 1974; Warner and Satir, 1974).


2008 ◽  
Vol 19 (3) ◽  
pp. 214-218 ◽  
Author(s):  
Franklin Delano Soares Forte ◽  
Suzely Adas Saliba Moimaz ◽  
Fábio Correia Sampaio

The aim of this study was to evaluate the urinary fluoride excretion of 2- to 7-year-old children exposed to different water fluoride concentrations in the city of Catolé do Rocha, PB, Brazil. Forty-two children were allocated to 3 groups according to the concentration of fluoride in the water: G1 (n=10; 0.5-1.0 ppm F), G2 (n=17; 1.1-1.5 ppm F) and G3 (n= 15; >1.51 ppm F). The study was carried out in two 1-week phases with 1-month interval between the moments of data collection: in the first phase, the children used a fluoride toothpaste (FT) (1,510 ppm F) for 1 week, whereas in the second phase a non-fluoride toothpaste (NFT) was used. The urine was collected in a 24-h period in each week-phase according to Marthaler's protocol. The urinary fluoride excretion data expressed as mean (SD) in µg/24 h were: G1-FT= 452.9 (290.2); G1-NFT= 435.1 (187.0); G2-FT= 451.4 (224.0); G2-NFT= 430.3 (352.5); G3-FT=592.3 (390.5); and G3-NFT=623.6 (408.7). There was no statistically significant difference between the water fluoride groups, and regardless of the week phase (ANOVA, p>0.05). The use of fluoride toothpaste (1,510 ppmF) did not promote an increase in urinary fluoride excretion. There was a trend, though not significant, as to the increase of urine fluoride concentration in relation to fluoride concentrations in the water. The excretion values suggest that some children are under risk to develop dental fluorosis and information about the appropriate use of fluoride is necessary in this area.


2016 ◽  
Vol 101 (5-6) ◽  
pp. 291-296 ◽  
Author(s):  
Mustafa Uysal ◽  
Gurkan Ozkoc ◽  
Filiz Bolat ◽  
Mehmet Turker ◽  
Mehmet Erdem

Apoptosis refers to cell death without inflammatory process, and is related to degenerative changes in joints. We hypothesized that zoledronic acid (ZA) would have a positive effect on chondrocyte viability and decreases in chondrocyte loss, which are important for the progression of degeneration. This study aimed to reveal the difference in time-dependent apoptotic changes in cartilage tissue in the anterior cruciate ligament (ACL) transection model of osteoarthritis (OA) in rat knees after treatment with zoledronic acid. We randomly divided 48 male Wistar albino rats into 6 groups. The knees of all rats except those in the control group underwent the operation for ACL transection. ZA for half of the rats and saline solution for the others was injected weekly into knees. Animals were killed at 0, 3, and 6 weeks after surgery. Apoptosis of chondrocytes were analyzed using the terminal deoxynucleotidyl transferase dUTP nick end labeling method. Comparison of groups was performed using Kruskal Wallis analysis and the Mann Whitney U test. Significant differences were observed between the groups treated with ZA and saline. ZA treatment significantly decreased the number of apoptotic cells in chondral tissue. ZA prevents time-dependent degenerative changes in chondral tissue by decreasing chondrocyte death. Intra-articular ZA may have the potential to treat and conserve chondral viability. ZA prevents chondrocyte loss and may play a therapeutic role in OA and conserving joint health. Further studies are needed to evaluate the potential of intra-articular ZA for the prevention or treatment of age-related degenerative changes.


2019 ◽  
Author(s):  
Chu Zhang ◽  
Chong-Hui Ying ◽  
siqin Sun ◽  
yuechun Wen ◽  
Zicheng Zhu

Abstract ● AIM : T o investigate the expression of nod-like receptor pyrin domain 3 (NLRP3) in lens anterior capsule of Uveitis associated with cataract and observe the ultrastructural changes of them . ● Methods: 17(22 eyes) cases of uveitis associated with cataract were selected a s experimental group and 1 0 (18 eyes) cases of age-related cataract were selected a s contro l group. The expressions of NLRP3, apoptosis-related speckle protein (ASC) and caspase-1 protein were tested by immunohistochemical and the ultrastructural changes of anterior capsul e was observed under electron microscope. ● Results: The expression of NLRP3 、 caspase-1 and ASC in the anterior capsu le of cataracts associated with uveitis was significantly higher than that of the control group, the difference was statistically significant (p < 0.05). The apoptotic changes of lens epithelial cells in uveitis associated with cataract were obvious, and the apoptotic changes of lens epithelial cells were mild in age-related cataract patients. ● Conclusion: Strongly postive expressed NLRP3 inflamma some and obvious apoptotic changes are founded in the lens epithelial cells of patients with uveitis associat ed with cataract, suggesting that NLRP3 inflamma some and the apoptosis of lens epithelial cells may play a role in the progress of uveitis associat ed with cataract.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Rong Rong ◽  
Osamu Ito ◽  
Nobuyoshi Mori ◽  
Yuma Tamura ◽  
Akihiro Sakuyama ◽  
...  

The (pro)renin receptor ((P)RR)-bound (pro)renin not only causes the generation of angiotensin II via the increased enzymatic activity, it also activates the receptor’s own intracellular signaling pathways up-regulating the expression of the profibrotic proteins. To clarify the regulation of (P)RR expression, the present study examined the effects of high salt diet and nitric oxide synthase (NOS) inhibition on the (P)RR expression in the kidney. The nephron segments were isolated from male Sprague-Dawley (SD) rats by microdissection and bulk isolation technique, and the (P)RR mRNA and protein expressions were examined by using reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. In adiition, 5 week-old, male SD rats were randomly divided into 3 groups: a control group, a high salt diet (HS) group and a Nω-Nitro-L-arginine (L-NAME) group, and each group was treated with vehicle, high salt diet (8%, NaCl), or L-NAME (600mg/ml in drinking water), respectively. After 4 weeks, the (P)RR expression in the kidney was compared among these groups. The (P)RR mRNA was expressed in the glomerulus (Glm), the proximal convoluted and straight tubule, the cortical and medullary thick ascending limb (TAL) and collecting duct. The (P)RR protein as well as mRNA was expressed widely in the nephron segments; the preglomerular arteriole, the Glm, the proximal tubules (PT), the medullary TAL (mTAL) and inner medullary collecting duct (IMCD). Compared with the control group, the (P)RR protein levels significantly increased in the kidney cortex of both HS group and L-NAME group by 96% (p<0.01) and 506% (p<0.01) and in the inner medulla of L-NAME group by 148% (p<0.05), but did not significantly change in the outer medulla of HS group or L-NAME group. HS increased the (P)RR protein levels in the Glm and PT by 48% (p<0.05) and 39% (p<0.01), but did not affect them in other nephron segments. These results indicated that (P)RR is expressed widely in the nephron segments and that HS and NOS inhibition upregulate the (P)RR expression in the kidney, suggesting roles of (P)RR in hypertensive kidney disorder.


2021 ◽  
Author(s):  
Man Zhao ◽  
Wenbo He ◽  
Can Tao ◽  
Beiyu Zhang ◽  
Shuai Wang ◽  
...  

Abstract The objective of this study was to reveal the effects of cadmium (Cd) on ultrastructural changes, oxidative stress, and transcriptome expression in the kidneys of laying hens. Seventy-two healthy Hy-Line brown laying hens at 41 weeks old were randomly allocated to four treatment groups with six replicates. The control group received a basal diet without additional Cd incorporation, and the other three treatment groups received diets supplemented with 15, 30, or 60 mg Cd /kg of feed. After 6 weeks of exposure the results show that administration of 60 mg/kg Cd significantly reduced (P < 0.05) eggshell thickness. With an increase in the Cd concentration in feed, the concentrations of renal Zn, Fe also had changed. Renal histopathology and ultrastructure also showed aggravated damage to glomeruli and renal tubules, and the deformation of nuclei and mitochondria in all Cd treatment groups. With an increase in Cd in feed, the activity of GPX and CAT was significantly reduced (P<0.05), while the activity of T-AOC was decreased (P<0.05) only in the 60 mg/kg Cd group. RNA-seq analysis revealed that 410 genes displayed differential expression (≥ 1.5-fold) in the 60 mg/kg supplementation group, compared to the control group. GO and KEGG pathway analysis results showed that Cd affected many genes involved in mitochondria and ion transport. In conclusion, this study elaborates the mechanisms underlying renal toxicity caused by Cd, which might provide target candidate genes for alleviating Cd poisoning in laying hens.


2021 ◽  
Author(s):  
Mauro Antonio Dall Agnol ◽  
Carla Battiston ◽  
Livia Maria Andalo Tenuta ◽  
Jaime Aparecido Cury

Although fluoride varnish (FV) and acidulated phosphate fluoride gel (APF-gel) are considered clinically effective to reduce caries, in vitro studies have shown that FV reacts slowly with enamel because most NaF present in the formulation is not solubilized in the FV. Therefore, we conducted a clinical study to evaluate if the time that FV remains on dental surfaces could overcome its slower chemical reactivity when compared with APF-gel. Sixty-eight volunteers were randomly allocated into four groups: Negative control (Control, no treatment), APF -gel application (1.23% F applied for 4 min), and FV application (Duraphat®, 2.26 % F) for 4 h (FV-4h) or 24 h (FV-24h). To evaluate fluoride formed and retained on enamel, acid biopsies were made on the buccal surfaces of the maxillary central incisors before, at the end of the application of fluoride products (immediately after gel application, or after 4 or 24 h of varnish application) and after 7 and 28 days. Fluoride concentration in dental biofilm was also analyzed before and up to 28 days after initial application. The data were analyzed by 2-way ANOVA, considering treatment and time as factors. The APF-gel and FV-24h groups formed greater fluoride concentration on enamel than the FV-4h and the control group at the end of application (p=0.0001), with no difference from each other (p=0.99). The groups did not differ regarding fluoride in biofilm, fluid (p=0.73) and solids (0.40). In conclusion, fluoride varnish needs to remain in contact with the teeth for prolonged times (>4 h) to reach the same reactivity obtained by a 4-min application of APF-gel.


2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Hongyang Jiang ◽  
Xintao Gao ◽  
Jianan Gong ◽  
Qian Yang ◽  
Ruzhu Lan ◽  
...  

Solute carrier family 26 member 6 (Slc26a6), which is mainly expressed in the intestines and kidneys, is a multifunctional anion transporter that is crucial in the transport of oxalate anions. This study is aimed at investigating the effect of Slc26a6 expression on oxalate-induced cell oxidation and crystal formation. Lentivirus transfection was used to upregulate or downregulate Slc26a6 expression in NRK cells. Cell viability and apoptosis, reactive oxygen species (ROS) and malondialdehyde (MDA) generation, and superoxide dismutase (SOD) activity were measured. Crystal adhesion and the cell ultrastructure were observed using light and transmission electron microscopy (TEM). Three groups of rats, normal control, lentivirus-vector, and lentivirus-small interfering RNA (lv-siRNA) groups, were used, and after lentivirus transfection, they were fed 1% ethylene glycol (EG) and 0.5% ammonium chloride (NH4Cl) for 2 weeks. Dihydroethidium (DHE), terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labeling (TUNEL), and von Kossa staining were performed, and nuclear factor κB (NFκB) and osteopontin (OPN) expression were measured. In the vitro study, compared to the control group, downregulated Slc26a6 NRK cells showed alleviation of the cell viability decrease, cell apoptosis rate, ROS generation, and SOD activity decrease after oxalate treatment. Crystal adhesion and vesicles were significantly less after oxalate exposure than in the untreated controls. Rats infected with lentivirus-siRNA exhibited attenuated SOD generation, cell apoptosis, and crystal formation in the kidneys. Increased phosphorylation of NFκB and OPN was involved in the pathological process. In conclusion, the results of the present study indicate that reducing the expression of Slc26a6 in the kidney may be a potential strategy for preventing stone formation.


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