Renal filtration, reabsorption and excretion of aluminium in the rat

1992 ◽  
Vol 82 (1) ◽  
pp. 13-18 ◽  
Author(s):  
C. J. Lote ◽  
J. A. Wood ◽  
H. C. Saunders

1. Plasma and urinary aluminium levels, and renal function, were investigated in a control group of rats (n = 5) and in two groups that received an intravenous bolus dose of aluminium chloride (either 25 μg or 800 μg of aluminium, n = 7 and 5, respectively). 2. In the control group (plasma aluminium concentration 76.8 ± 14.2 ng/ml), 59.4 ± 3.5% of the plasma aluminium was ultrafilterable. The percentage ultrafilterable after the administration of 25 μg of aluminium was 41.9 ± 7.8 (plasma concentration 154.3 ± 18.6 ng/ml). However, after administration of 800 μg of aluminium, to give a plasma concentration of 19800 ± 2956 ng/ml, only 1.06 ± 0.13% was ultrafilterable. 3. Such results have generally been interpreted as indicating an increase in protein-binding of aluminium with increasing aluminium concentration. In buffered aqueous solutions of aluminium chloride at pH 7.4, with an aluminium concentration of 189 ± 6 ng/ml, 96.12 ± 0.02% was ultrafilterable (n = 6). This concentration is comparable with that attained in the low-dose (25 μg) aluminium group of animals and suggests that the difference between the ultrafilterable percentage of aluminium in plasma compared with that in aqueous solution is indeed due to the binding of aluminium to high Mr material (proteins). In contrast, however, in an aqueous buffered (pH 7.4) solution containing 28200 ng of aluminium/ml, only 1.05 ± 0.09% was ultrafilterable. This indicates insolubility (i.e. colloid formation) of the aluminium at this high concentration. The same percentage (1.06 ± 0.13) was ultrafilterable from plasma from the high-dose (800 μg) aluminium group with a plasma aluminium concentration of 19 800 ± 2956 ng/ ml. This low ultrafilterable fraction is thus attributable to the insolubility of aluminium at this concentration, rather than to protein binding. 4. The fractional excretion of aluminium in the control group was approximately 10%. It was somewhat higher in the low-dose aluminium group, and reached 53% in the high-dose aluminium group. Nevertheless, it is clear that the kidneys are inefficient at excreting aluminium, so that after aluminium administration there is a prolonged period (several hours) during which the plasma aluminium concentration remains elevated and thus tissue deposition may occur.

Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.


2016 ◽  
Vol 44 (6) ◽  
pp. 243
Author(s):  
Ariyanto Harsono

Background Evidence begin to accumulate that high-dose sub-lingual immunotherapy (SLIT) is as effective as subcutaneousimmunotherapy (SIT) in the treatment of childhood asthma.Since the capacity of sublingual area is similar whether the doseis high or low, the efficacy of low dose may be important to bestudied.Objective To investigate the efficacy of low-dose sublingual im-munotherapy in the treatment of childhood asthma.Methods Parents signed informed consent prior to enrollment,after having received information about the study. Patients weremoderate asthma aged 6-14 years with disease onset of lessthan 2 years before the commencement of the study and peakexpiratory flow rate (PEFR) variability of more than 15%. Pa-tients were randomly allocated into group A, B, and C whoreceived subcutaneous immunotherapy, low-dose sublingualimmunotherapy, and conventional asthma therapy, respectively.Randomization was stratified into two strata according to agei.e., 6-11 years or 11-14 years. Patients of each stratum wererandomized in block of three for each group. At the end of threemonths, lung function tests were repeated. The primary outcomewas PEFR variability at the end of the study. The study wasapproved by the Ethics Committee of Soetomo HospitalSurabaya.Results Distribution of variants as represented by sex, age,eosinophil count, and total IgE concentration were normal inthe three groups. PEFR variability decreased significantly from16.97+0.81 to 8.50+5.08 and 17.0+0.87 to 8.40+4.72 in groupreceiving SIT and SLIT, respectively (p<0.05), but decreasednot significantly from 17.00+0.83 to 10.82+0.5.41 in control group(p>0.05).Conclusion Low-dose SLIT is as efficacious as SIT in the treat-ment of moderate asthma in children


2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.


Author(s):  
Meilinah Hidayat ◽  
Sijani Prahastuti ◽  
Estherolita Dewi ◽  
Dewi Safitri ◽  
Siti Farah Rahmawati ◽  
...  

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.


2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).


1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fangui Zhao ◽  
Wenjun Wang

Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation.


2020 ◽  
Author(s):  
Tao Hong ◽  
Hao Chen ◽  
Li Liu ◽  
Weiqi Liu ◽  
Longxue Li ◽  
...  

Abstract Background Coix seed is a traditional Chinese medicine with pharmacological effects and food efficacy. It is well-know and widely used in China and other Asian countries. Fayiren is a new artillery material processed from Coix Seed. This is the first study of the diuretic activities of Fayiren and coix seed in normal rats. Methods Forty-eight rats were randomly divided into 6 groups (8 rats/group) according to body mass and urine volume stratification, namely model (physiological saline) group, positive control (furosemide 20 mg/kg) group, coix seed (1666 mg/kg) group, low-dose of Fayiren group (166 mg/kg) and high-dose Fayiren group (1666 mg/kg). Rats were fasted for 16 h before the experiment, with normal water supply. Immediately after administration, each group of rat was placed in a metabolic cage, and urine was collected once after every hour for a total of 6 times. The urine volume at each time point for collection was measured, and then totaled. After the 6 h recording procedure, the treatments were administered once a day and the urine was collected at the 24th, 48th, 72th, 96th, 110th, 134th, and 158th hours from the start respectively. The urine pH and Na +, K +, Ca 2+, Cl - concentrations at each time point of each group of rats were measured. The contents of ALD, ANP, ADH, Na+-K+-ATPase, the gene expression and protein levels of AQP1, AQP2 and AQP3 in urine of rats in each group were determined. SPSS22.0 statistical software was used to analyze the experimental data. One way ANOVA and multiple comparisons between LSD groups were performed. The difference is considered significant When p < 0.05 or p < 0.01. Results After the administration of Fayiren and coix seed, compared with normal rats, the total output of urine in the high-dose coix seed & Fayiren group and the positive control group both increased; In addition, the contents of Na+ and Cl-in urine in these groups increased as well. However, the content of K+ did not increase in all groups. Contents of ALD and ADH was decreased and increased contents of ANP observed in urine in both high-dose and low-dose Fayiren groups with significant differences from model group (P < 0.05). Coix seed significantly reduced ADH and increased ANP levels compared with model group (P < 0.05). There was no obvious change in the urine pH content in urine of all rats. All the aquaporin (AQP1, AQP2, and AQP3) contents were decreased comparing to the model group, the coix seed group, as well as the Fayiren group. The effect of coix seed was particularly notable on AQP2, and the difference was significant against the Furosemide group (P < 0.05). By contrast, Fayiren showed greater effects on AQP1 and AQP3, with statistically significant difference comparing to the model group (P༜0.05). Conclusions This study will provide experimental evidence for explaining the different mechanisms of diuretic effects in natural medicine use of coix seed and artillery material processed from Coix Seed. The Fayiren may affect the reabsorption of water in the kidney through mechanisms related to increased ANP secretion,decreased ALD and ADH secretion in urine, and it significantly affect the expression of aquaporin 1 and aquaporin 3. However, coix seed may increase ANP but decreased ADH secretion, further affecting the expression of aquaporin2 and exert diuretic effect.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tao Hong ◽  
Long-Xue Li ◽  
Xiao-ping Han ◽  
Jing-liang Shi ◽  
Cai-yun Dan ◽  
...  

In this study, the effects of Astragalus membranaceus oral solution on lifespan and learning and memory abilities of honey bees were evaluated. Two groups of bees were fed with sucrose syrup (50%) containing low dose (1.33%) and high dose (13.3%) of A. membranaceus oral solution, respectively. The proboscis extension response (PER) analysis was applied to examine the learning and memory capabilities of bees. Two genes related to memory formation in honey bees were determined by real-time PCR. High dose (13.3%) of A. membranaceus significantly decreased the mean lifespan of bees compared to the bees fed with low dose (1.33%) and control bees. No significant differences in lifespan of bees were found between low-dose-fed bees and control bees. The results of PER experiments showed apparent improvement in the memorizing ability of the high-dose group (in comparison with the control group). Moreover, the relative expression levels of Nmdar1 in the low-dose group and control group were significantly lower than those in the high-dose group. It is preliminarily concluded that A. membranaceus has an adverse effect on the mean lifespan of honey bees but might be helpful in strengthening memories.


2019 ◽  
Vol 74 (2) ◽  
pp. 353-370 ◽  
Author(s):  
Li Tian ◽  
Weibin Qian ◽  
Qiuhai Qian ◽  
Wei Zhang ◽  
Xinrui Cai

Abstract Gingerol, a biologically active component in ginger, has shown antiemetic properties. Our study aimed to explore the underlying mechanisms of gingerol on protecting rats and minks from chemotherapy-induced nausea and vomiting. The preventive impact of gingerol was evaluated in the pica model of rats and the vomiting model of minks induced by cisplatin at every 6 h continuously for a duration of 72 h. Animals were arbitrarily separated into blank control group, simple gingerol control group, cisplatin control group, cisplatin + metoclopramide group, cisplatin + three different doses gingerol group (low-dose; middle-dose; high-dose). The area postrema as well as ileum damage were assessed using H&E stain. The levels of 5-TH, 5-HT3 receptor, TPH, SERT, SP, NK1 receptor, PPT, NEP, DA, D2R, TH, and DAT were determined using immunohistochemistry or qRT-PCR in rats and minks. All indicators were measured in the area postrema along with ileum. The kaolin intake by rats and the incidence of CINV of minks were significantly decreased after pretreatment with gingerol in a dosage-dependent way for the duration of 0–24-h and 24–72-h. Gingerol markedly decreased the levels of 5-TH, 5-HT3 receptor, TPH, SP, NK1 receptor, PPT, DA, D2R, TH, alleviated area postrema as well as ileum damage, and increased the accumulation of SERT, NEP, DAT in the area postrema along with ileum of rats and minks. Gingerol alleviates cisplatin-induced kaolin intake of rats and emesis of minks possibly by regulating central and peripheral 5-HT system, SP system and DA system. Graphic abstract


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