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Sample records for adult rat kidneys

  1. Hypertension after bilateral kidney irradiation in young and adult rats

    SciTech Connect

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-09-01

    The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension.

  2. Histological effects of chronic consumption of soda pop drinks on kidney of adult Wister rats.

    PubMed

    Adjene, Josiah Obaghwarhievwo; Ezeoke, Joseph Chigozie; Nwose, Ezekiel Uba

    2010-05-01

    Health concerns over soda pop drinks have been severally report. However, histological perspectives are not very common. The objective of this study is to investigate histological effect of chronic consumption of soda pop drinks on the kidney of adult Wistar rats. The rats of both sexes (n = 24), with average weight of 200g were randomly assigned into two treatment (A & B) (n=16) and Control (c) (n=8) groups. The rats in the treatment group (A) received a brand of soda pop drink on a daily basis for thirty days. The rats in treatment group (B) received another brand of soda drink, while the control group (C) received equal amount of water for the same period. The rats were given the drinks as well as feeds liberally for thirty days, and sacrificed by cervical dislocation on the thirty-first day of the experiment. The kidney was carefully dissected out and quickly fixed in 10% formal saline for histological study. The findings indicate that rats in the treated groups (A&B) showed some varying degree of distortion and disruption of the renal structure. There are observable diffuse signs of glomerulonephritis with some congestion and tubular necrosis as compared to the control group. Chronic consumption of soda pop drinks may affect the microanatomy of the kidney of adult Wistar rats. Further study aimed at corroborating these observations in humans is warranted.

  3. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    PubMed Central

    Eweka, Andrew Osayame; Eweka, Abieyuwa

    2010-01-01

    Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24), with average weight of 220g were randomly assigned into two treatments (A & B) of (n=16) and Control (c) (n=8) groups. The rats in the treatment groups (A & B) received 0.1g (500mg/kg body weight) and 0.2g (1000mg/kg body weight) of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c) received equal amount of feeds daily without nutmeg added for forty-two days. The growers’ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings. PMID:22624138

  4. The effects of pomegranate extract on normal adult rat kidney: A stereological study

    PubMed Central

    Mansouri, Esrafil; Basgen, John; Saremy, Sadegh

    2016-01-01

    Pomegranate (Punica granatum L.) has been used widely in the traditional medicine of various civilizations for more than 5000 years. The pomegranate tree has several parts; each part has useful medicinal effects. Previous studies have demonstrated the antibacterial, antioxidant, and anti-inflammatory properties of pomegranate. The aim of the present study was to determine whether administration of pomegranate extract could result in morphometric changes in the kidneys of rats. Eighteen male rats (180-200 g) were divided into three groups that received either: G1, distilled water; G2, 250 mg kg-1 pomegranate extract; and G3, 500 mg kg-1 pomegranate extract via oral gavages daily for eight weeks. At the end of eight weeks, the rats were euthanized and their kidneys were removed and processed for morphometric analyses. In rats received pomegranate extract, the kidney weight, kidney weight/body weight ratio, cortex v/lume and glomerular volume were increased (p < 0.05), while, medulla volume and the number of glomeruli per kidney did not change. No pathological lesions were observed in the kidney. Therefore, pomegranate hydro-alcoholic extract at doses of 250 and 500 (mg kg-1) increased the volume of some parts of the kidney; however, it did not cause any pathological changes in the kidney. PMID:27226880

  5. Nitraria retusa fruit prevents penconazole-induced kidney injury in adult rats through modulation of oxidative stress and histopathological changes.

    PubMed

    Chaâbane, Mariem; Koubaa, Mohamed; Soudani, Nejla; Elwej, Awatef; Grati, Malek; Jamoussi, Kamel; Boudawara, Tahia; Ellouze Chaabouni, Semia; Zeghal, Najiba

    2017-12-01

    Nitraria retusa (Forssk.) Asch. (Nitrariaceae) is a medicinal plant which produces edible fruits whose antioxidant activity has been demonstrated. The current study elucidates the potential protective effect of N. retusa fruit aqueous extract against nephrotoxicity induced by penconazole, a triazole fungicide, in the kidney of adult rats. Adult Wistar rats were exposed either to penconazole (67 mg/kg body weight), or to N. retusa extract (300 mg/kg body weight) or to their combination. Penconazole was administered by intra-peritoneal injection every 2 days from day 7 until day 15, the sacrifice day, while N. retusa extract was administered daily by gavage during 15 days. Oxidative stress parameters, kidney biomarkers and histopathological examination were determined. Nitraria retusa extract administration to penconazole treated rats decreased kidney levels of malondialdehyde (-10%), hydrogen peroxide (-12%), protein carbonyls (PCOs, -11%) and advanced oxidation protein products (AOPP, -16%); antioxidant enzyme activities: catalase (-13%), superoxide dismutase (-8%) and glutathione peroxidase (GPx, -14%), and the levels of non-enzymatic antioxidants: non-protein thiols (-9%), glutathione (-7%) and metallothionein (-12%). Furthermore, this plant extract prevented kidney biomarker changes by reducing plasma levels of creatinine, urea, uric acid and LDH and increasing those of ALP and GGT. Histopathological alterations induced by penconazole (glomeruli fragmentation, Bowman's space enlargement, tubular epithelial cells necrosis and infiltration of inflammatory leucocytes) were attenuated following N. retusa administration. Our results indicated that N. retusa fruit extract had protective effects against penconazole-induced kidney injury, which could be attributed to its phenolic compounds.

  6. [Effects of TiO₂ nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats].

    PubMed

    Wang, Yun; Chen, Zhang-jian; Ba, Te; Pu, Ji; Cui, Xiao-xing; Jia, Guang

    2014-06-18

    To compare the effect of TiO₂ nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats. Forty-eight SD male rats, half in 4-week (youth) old and half in 9-week (adult) old rats, were randomly divided into 8 groups, which were exposed to TiO₂ nanoparticles [(75 ± 15) nm, anatase] through intragastric administration at 0, 10, 50 and 200 mg/kg body weight every day for 30 days. The liver and kidney tissues were collected for antioxidant function and element content analysis. 200 mg/kg TiO₂ nanoparticles exposure significantly increased the liver total superoxide dismutase (T-SOD) activity and the kidney reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios in young rats, and significantly decreased the liver Mo, Co, Mn and P contents and the kidney Rb and Na contents in young rats. 200 mg/kg TiO₂ nanoparticles exposure significantly increased GSH/GSSG ratios and Rb contents and decreased Na contents in the liver of adult rats. No significantly difference was found in antioxidant indexes and elements content in the kidney of adult rats between three experimental groups and control group. TiO₂ nanoparticles can enhance the antioxidant capacity and decrease the elements content in rat liver and kidney tissues. The liver is the more sensitive target organ and the young animals are more susceptible to TiO₂ nanoparticles toxicity by the oral routes.

  7. Elemental imaging of kidneys of adult rats exposed to uranium acetate

    NASA Astrophysics Data System (ADS)

    Homma-Takeda, S.; Terada, Y.; Nakata, A.; Sahoo, S. K.; Yoshida, S.; Ueno, S.; Inoue, M.; Iso, H.; Ishikawa, T.; Konishi, T.; Imaseki, H.; Shimada, Y.

    2009-06-01

    Concern about the toxicity of depleted uranium for military use has increased recently. Renal toxicity is the hallmark effect of uranium exposure. However, the dynamics and distribution of uranium in the kidney are not well understood. Here, we determined the precise distribution of uranium and essential elements in the rat kidney using microbeam scanning particle-induced X-ray emission (micro-PIXE) and synchrotron radiation X-ray fluorescence (SR-XRF). Uranium accumulation in the rat kidney reached a maximum at 1 day after the subcutaneous (s.c.) administration of 2 mg U/kg of uranium acetate and then gradually decreased. At 3 h after administration, uranium was distributed mainly in the proximal tubules of the inner zone of the cortex and in the outer stripe of the outer medulla, and absorbed by the proximal tubule epithelium. Iron was localized more in the inside of the outer medulla than uranium, while phosphorus, potassium, sulfur and zinc were equally distributed in the cortex and the outer stripe of the outer medulla. At 3 days after administration, the number of apoptotic cells increased and cells were lost from the proximal tubules. Uranium was detectable mainly in the outer stripe of the outer medulla at 15 days, suggesting that the renal distribution of uranium is site-selective and causes site-specific renal lesions.

  8. Carvedilol exacerbate gentamicin-induced kidney mitochondrial alterations in adult rat.

    PubMed

    Félix, Luís; Oliveira, M M; Videira, Romeu; Maciel, Elisabete; Alves, Nuno D; Nunes, Fernando M; Alves, Anabela; Almeida, José M; Domingues, M Rosário M; Peixoto, Francisco P

    2017-02-01

    Gentamicin is an aminoglycoside antibiotic widely used to treat many types of bacterial infections. Although its properties, his clinical use is limited due to the occurrence of nephrotoxicity, which has been related to mitochondrial dysfunction. Carvedilol, an antihypertensive drug with strong antioxidant properties, has been tested in order to prevent gentamicin nephrotoxicity. This study aimed to test this hypothesis using a rat model of gentamicin-induced nephrotoxicity. Animals were treated subcutaneously with DMSO (control) (0.4%/kg/24h bw) for 11days; with carvedilol (2mg/kg/24h bw) for 11days; with gentamicin (60mg/kg/24h bw) for the last 8days and with carvedilol (2mg/kg/24h bw) for 11days and with gentamicin (60mg/kg/24h bw) for the last 8days. Estimations of urine creatinine, urine carboxylic acids, blood urea, serum creatinine and glomerular filtration rate were carried out after the last administered dose of gentamicin. Mitochondria functionality was analyzed by monitoring its bioenergetics function and cardiolipin oxidized products were analyzed by ESI-MS. The kidneys were also examined for morphological changes. Gentamicin caused marked nephrotoxicity and mitochondrial dysfunction as evidenced by several mitochondrial parameters. Carvedilol did not induce significant changes while the co-treatment exacerbated the negative effect of gentamicin although maintaining ATP levels and membrane potential. Kidneys from gentamicin treated rats, with and without carvedilol, showed necrosis of tubular cells in renal cortex. Higher values on relative abundance of cardiolipin oxidation products identified as [M-2H](2-) ions, at m/z 771 were observed in the groups treated with gentamicin. The observed effects were associated to a possible interaction of carvedilol with F1F0-ATP synthase that merit further investigation. In conclusion, carvedilol may contribute to the exacerbation of renal dysfunction induced by gentamicin, at least in some physiological and

  9. Epidermal growth factor receptor activation in developing rat kidney.

    PubMed

    Cybulsky, A V; Goodyer, P R; McTavish, A J

    1994-09-01

    Epidermal growth factor (EGF) binding increases in late-gestational rat kidney and then falls toward basal adult levels postnatally during the 1st wk. We report that the increase in EGF binding is accompanied by an increase in EGF receptor (EGFR) protein and activation of EGFR tyrosine kinase. Multiple proteins were endogenously tyrosine phosphorylated in kidney membranes from fetal rats, and the phosphorylation pattern was similar in rats ranging from 16 to 21 days of gestation. Tyrosine phosphorylation was, however, almost undetectable in 12-wk adult rat kidneys (controls). Among the phosphoproteins in fetal kidney, a prominent 170-kDa protein was identified as EGFR. Endogenous tyrosine phosphorylation of EGFR (reflecting receptor activation) was 30-fold higher in fetal kidney membranes than in adult (3- to 7-fold higher when adjusted for differences in EGF binding or EGFR protein content). The EGFR substrate, phospholipase C-gamma 1, was tyrosine phosphorylated in fetal kidneys but not adult, and a greater proportion was membrane-associated in fetal kidneys, consistent with activation of phospholipase C-gamma 1. Thus EGFR tyrosine kinase activity is increased in late-gestational rat kidney. Induction and activation of EGFR may mediate perinatal renal cell growth and development.

  10. Effects of co-exposure to imidacloprid and gibberellic acid on redox status, kidney variables and histopathology in adult rats.

    PubMed

    Lafi, Bornia; Chaâbane, Mariem; Elwej, Awatef; Grati, Malek; Jamoussi, Kamel; Mnif, Hela; Boudawara, Tahia; Ketata Bouaziz, Hanen; Zeghal, Najiba

    2017-09-06

    Data on the individual nephrotoxic effects of imidacloprid (IMI) and gibberellic acid (GA3) are scarce. Moreover, there is a lack of information about their combined effects on the renal tissue. Our study investigated the effects of IMI and GA3 separately or together on rats kidney. IMI (64 mg/kg bw) was given for 3 weeks by gavage either individually or in combination with GA3 (200 mg/L) via drinking water. IMI associated or no with GA3 increased the levels of kidney malondialdehyde, advanced oxidation protein products, protein carbonyls and metallothionein, plasma creatinine, urea, blood urea nitrogen and lactate dehydrogenase activity. A decline of kidney uric acid level and antioxidant status was also observed. All these changes were supported by histopathological observations. Our results highlighted the role of IMI and/or GA3-induced nephrotoxicity. Co-exposure to IMI and GA3 exhibited synergism in biochemical kidney variables and histopathology and antagonism in physical and morphological parameters.

  11. Renin and angiotensinogen gene expression in maturing rat kidney

    SciTech Connect

    Gomez, R.A.; Lynch, K.R.; Chevalier, R.L.; Wilfong, N.; Everett, A.; Carey, R.M.; Peach, M.J. )

    1988-04-01

    To determine whether angiotensinogen (A{sub o}) and renin are synthesized by the immature kidney and to assess the changes in intrarenal reinin distribution that occur with maturation, the kidneys from 24 newborn and 12 adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were processed for renin immunocytochemistry using a highly specific anti-rat renin antibody. Kidney renin and A{sub o} relative mRNA levels (mRNA/total RNA) were detected by Northern and dot blot techniques, using full-length rat renin and A{sub o} cDNAs. Renal renin concentration (RRC) was measured by radioimmunoassay of angiotensin I (ANG I) and expressed as ng ANG I{center dot}h{sup {minus}1}{center dot}mg protein{sup {minus}1} in the incubation media. RRC was higher in newborn than in adult SHR (979 {+-} 164 vs. 206 {+-} 47) and WKY. In the newborn kidneys of both rat strains, renin was distributed throughout the entire length of the afferent arterioles and interlobular arteries, whereas in the adult kidneys renin was confined to the classical juxtaglomerular position. With maturation, there was a decrease in the proportion of immunoreactive juxtaglomerular apparatuses and arterial segments that contained renin. Kidney renin mRNA levels were 7.9-fold higher in the newborn than in the adult animals. A{sub o} mRNA was detected in the newborn and adult kidneys of both rat strains. This study demonstrates conclusively that both renin and A{sub o} genes are expressed in the newborn kidney, providing evidence for a local renin-angiotensin system that is subjected to developmental changes.

  12. Effects of testosterone on mean arterial pressure and aquaporin (AQP)-1, 2, 3, 4, 6 and 7 expressions in the kidney of orchidectomized, adult male Sprague-Dawley rats.

    PubMed

    Loh, Su Yi; Giribabu, Nelli; Gholami, Khadijeh; Salleh, Naguib

    2017-01-15

    We hypothesized that higher blood pressure in males than females could be due to testosterone effects on aquaporin (AQP) expression in kidneys. Orchidectomized adult male Sprague-Dawley (SD) rats received seven days subcutaneous testosterone treatment (125 μg/kg/day or 250 μg/kg/day), with or without flutamide or finasteride. Following completion of treatment, MAP was determined in rats under anaesthesia via carotid artery cannulation. In another cohort of rats, kidneys were removed following sacrifice and AQP-1, 2, 3, 4, 6 and 7 protein and mRNA levels were determined by Western blotting and Real-time PCR respectively. Distribution of AQP subunits' protein in the nephrons were visualized by immunofluorescence. Testosterone caused MAP, AQP-1, 2, 4, 6 and 7 protein and mRNA levels in kidneys to increase while AQP-3 protein and mRNA levels in kidneys to decrease (p < 0.05). AQP-1 and 7 were found to be distributed in the proximal convoluted tubule (PCT) while AQP-2, 3, 4 and 6 were found to be distributed in the collecting ducts (CD). Effects of testosterone were antagonized by flutamide and finasteride. Elevated expression of AQP-1, 2, 4, 6 and 7 under testosterone influence in kidneys could lead to increase H2O reabsorption which eventually lead to increase in blood pressure. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. [Membranous kidney diseases in adults].

    PubMed

    Sobarzo Toro, Martín; Vilches, Antonio

    2004-01-01

    Membranous nephropathy is the most common histologic phenotype associated with the primary nephrotic syndrome in adults and the second most common etiological diagnosis in over sixteen hundred renal biopsies on native kidneys processed at our institution over a 30 year period. Renal survival at 10 years is about 70%, but the course of the disease is related to a series of factors which have constituted the basis for mathematical models developed to predict the natural history in a given individual. These factors are gender, age, renal function at the time of diagnosis, presence of the nephrotic syndrome, high blood pressure and the degree of structural damage. Although in low risk patients a period of observation and the use of ACE inhibitors is a reasonable option, most nephrologists would elect to use pharmacological treatment to induce remissions of proteinuria and preserve renal function. The use of steroids and cytotoxic agents in alternating monthly cycles over six months is firmly supported by controlled, randomized clinical trials. If patients are resistant to this regimen or clinical considerations indicate it may be inappropriately toxic, the use of cyclosporin over 6 to 12 months is also a good choice, and it has been shown to be useful even in the context of deteriorating renal function. Mycophenolate mofetil and possibly rituximab may be options of last resort before considering the patient resistant to therapy. At all times, treatment of hypertension, non-specific antiproteinuric measures, and preventing complications of the nephrotic state should be top priorities in the overall therapeutic strategy.

  14. Dissection of the adult zebrafish kidney.

    PubMed

    Gerlach, Gary F; Schrader, Lauran N; Wingert, Rebecca A

    2011-08-29

    Researchers working in the burgeoning field of adult stem cell biology seek to understand the signals that regulate the behavior and function of stem cells during normal homeostasis and disease states. The understanding of adult stem cells has broad reaching implications for the future of regenerative medicine. For example, better knowledge about adult stem cell biology can facilitate the design of therapeutic strategies in which organs are triggered to heal themselves or even the creation of methods for growing organs in vitro that can be transplanted into humans. The zebrafish has become a powerful animal model for the study of vertebrate cell biology. There has been extensive documentation and analysis of embryonic development in the zebrafish. Only recently have scientists sought to document adult anatomy and surgical dissection techniques, as there has been a progressive movement within the zebrafish community to broaden the applications of this research organism to adult studies. For example, there are expanding interests in using zebrafish to investigate the biology of adult stem cell populations and make sophisticated adult models of diseases such as cancer. Historically, isolation of the zebrafish adult kidney has been instrumental for studying hematopoiesis, as the kidney is the anatomical location of blood cell production in fish. The kidney is composed of nephron functional units found in arborized arrangements, surrounded by hematopoietic tissue that is dispersed throughout the intervening spaces. The hematopoietic component consists of hematopoietic stem cells (HSCs) and their progeny that inhabit the kidney until they terminally differentiate. In addition, it is now appreciated that a group of renal stem/progenitor cells (RPCs) also inhabit the zebrafish kidney organ and enable both kidney regeneration and growth, as observed in other fish species. In light of this new discovery, the zebrafish kidney is one organ that houses the location of two

  15. Dissection of the Adult Zebrafish Kidney

    PubMed Central

    Wingert, Rebecca A.

    2011-01-01

    Researchers working in the burgeoning field of adult stem cell biology seek to understand the signals that regulate the behavior and function of stem cells during normal homeostasis and disease states. The understanding of adult stem cells has broad reaching implications for the future of regenerative medicine1. For example, better knowledge about adult stem cell biology can facilitate the design of therapeutic strategies in which organs are triggered to heal themselves or even the creation of methods for growing organs in vitro that can be transplanted into humans1. The zebrafish has become a powerful animal model for the study of vertebrate cell biology2. There has been extensive documentation and analysis of embryonic development in the zebrafish3. Only recently have scientists sought to document adult anatomy and surgical dissection techniques4, as there has been a progressive movement within the zebrafish community to broaden the applications of this research organism to adult studies. For example, there are expanding interests in using zebrafish to investigate the biology of adult stem cell populations and make sophisticated adult models of diseases such as cancer5. Historically, isolation of the zebrafish adult kidney has been instrumental for studying hematopoiesis, as the kidney is the anatomical location of blood cell production in fish6,7. The kidney is composed of nephron functional units found in arborized arrangements, surrounded by hematopoietic tissue that is dispersed throughout the intervening spaces. The hematopoietic component consists of hematopoietic stem cells (HSCs) and their progeny that inhabit the kidney until they terminally differentiate8. In addition, it is now appreciated that a group of renal stem/progenitor cells (RPCs) also inhabit the zebrafish kidney organ and enable both kidney regeneration and growth, as observed in other fish species9-11. In light of this new discovery, the zebrafish kidney is one organ that houses the

  16. INORGANIC CATIONS IN RAT KIDNEY

    PubMed Central

    Tandler, C. J.; Kierszenbaum, A. L.

    1971-01-01

    For localization of pyroantimonate-precipitable cations, rat kidney was fixed by perfusion with a saturated aqueous solution of potassium pyroantimonate (pH about 9.2, without addition of any conventional fixative). A remarkably good preservation of the tissue and cell morphology was obtained as well as a consistent and reproducible localization of the insoluble antimonate salts of magnesium, calcium, and sodium. All proximal and distal tubules and glomeruli were delimited by massive electron-opaque precipitates localized in the basement membrane and, to a lesser extent, in adjacent connective tissue. In the intraglomerular capillaries the antimonate precipitate was encountered in the basement membranes and also between the foot processes. In addition to a more or less uniform distribution in the cytoplasm and between the microvilli of the brush border, antimonate precipitates were found in all cell nuclei, mainly between the masses of condensed chromatin. The mitochondria usually contained a few large antimonate deposits which probably correspond to the so-called "dense granules" observed after conventional fixations. PMID:4106544

  17. Radiation damage in rat kidney microvasculature.

    PubMed

    Nelson, A C; Shah-Yukich, A; Babayan, R

    1984-01-01

    Scanning electron microscopy (SEM) combined with a specialized polymer injection casting technique permits the analysis of radiation induced damage in rat kidney glomeruli. A lead shielding device is constructed to enable the irradiation of the living rat left kidney, while the remainder of the animal is shielded from the dose, the right kidney serves as a control. The source of radiation is 137Cs which produces 0.66 MeV gamma-rays to achieve a kidney dose of 100 rad and 5000 rad in these experiments. Radiation damage to kidney glomeruli is assessed at intervals of 0, 1, 3 and 7 days post-irradiation at the two dose levels. It is found that radiation damage to kidney glomeruli is expressed morphologically at 7 days post-irradiation at the 100 rad dose level, while glomerular damage is apparent as early as 3 days post-irradiation at the 5000 rad dose level. Moreover, by 7 days post-irradiation with a 5000 rad dose, the kidney glomerulus thoroughly degenerates to a leaky fused mass of vessels. From a morphological viewpoint, kidney glomeruli are significantly more sensitive to radiation than surrounding vasculature. The methods developed here for assessment of radiation damage are highly repeatable and could serve as a standard technique in radiobiology.

  18. Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

    PubMed Central

    Ali, Quaisar

    2016-01-01

    We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions. PMID:27528887

  19. Stroke in adult polycystic kidney disease.

    PubMed Central

    Rivera, M.; Gonzalo, A.; Gobernado, J. M.; Orte, L.; Quereda, C.; Ortuño, J.

    1992-01-01

    In order to assess the incidence of acute cerebrovascular events, 142 patients with adult polycystic kidney disease were retrospectively reviewed. Fourteen patients (9.8%) had 19 cerebral attacks. Six patients (4.2%) had intracranial haemorrhage attacks (three ruptured intracranial aneurysms and three cerebral haemorrhages). Ischaemic events occurred in nine patients (five cerebral infarctions and four transient ischaemic attacks). Patients with ischaemic attacks had a better outcome than patients with haemorrhagic events even when transient ischaemic attacks were excluded. Patients with ruptured intracranial aneurysms were younger. Cerebral complications are an important cause of morbidity and mortality in patients with adult polycystic kidney disease. They can prove disabling prior to or after dialysis and transplantation. PMID:1480536

  20. Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

    PubMed

    Chang, N K; Gu, J; Gu, S; Osorio, R W; Concepcion, W; Gu, E

    2015-06-01

    Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery.

  1. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    SciTech Connect

    Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  2. Defining high risk in adult kidney transplantation.

    PubMed

    2009-09-01

    Because identifiable factors contribute to allograft loss, and because no consensus has been reached on the definition of high risk, an interdisciplinary group of nurses, physicians, pharmacists, and social workers was convened in May 2008. Participants sought to reach consensus about the current state of science and best practices related to the definition and management of high-risk kidney transplant recipients. An expert facilitator with extensive experience in leading consensus teams guided consensus-building activities, which included discussion and small-group work. This consensus group conceptualized the definition of the "high-risk" kidney transplant recipient and provided information to guide the multidisciplinary team in their assessment of these patients before and after transplant. Three key areas, which were conceptualized as independent scales, had a substantial impact on outcomes: (1) transplant recipient medical factors, (2) donor and recipient immunological factors, and (3) transplant recipient psychosocial factors. Though depicted separately, alteration of a specific risk on one scale could influence some risk factors on another scale. In addition, the kidney allograft itself must be considered in the assessment of high risk. The continuum of risk described here should be useful to transplant clinicians in their assessment of high-risk adult kidney transplant patients, may aid centers in developing a more complete definition of high risk, and may lead to risk-reduction efforts.

  3. Co-exposure to aluminum and acrylamide disturbs expression of metallothionein, proinflammatory cytokines and induces genotoxicity: Biochemical and histopathological changes in the kidney of adult rats.

    PubMed

    Ghorbel, Imen; Maktouf, Sameh; Fendri, Nesrine; Jamoussi, Kamel; Ellouze Chaabouni, Semia; Boudawara, Tahia; Zeghal, Najiba

    2016-09-01

    The individual toxic effects of aluminum and acrylamide are known but there is no data on their combined effects. The present study investigates the toxic effects after combined exposure to these toxicants on: (i) oxidative stress during combined chronic exposure to aluminum and acrylamide on kidney function (ii) correlation of oxidative stress with metallothionein (MT) and inflammatory cytokines expression, DNA damage, and histopathological changes. Rats were exposed to aluminum (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage either individually or in combination for 3 weeks. Exposure rats to aluminum chloride or acrylamide alone and in combination induced nephrotoxicity, as evidenced by a decrease in the 24-h urine volume and uric acid levels in plasma and an increase of plasma creatinine, urea, and blood urea nitrogen levels. Nephrotoxicity was objectified by a significant increase in malondialdehyde level, advanced oxidation protein, and protein carbonyl contents, whereas reduced glutathione, nonprotein thiol, vitamin C levels, catalase, and glutathione peroxidase activities showed a significant decline. Superoxide dismutase activity and its gene expression were increased. Aluminum and acrylamide co-exposure exhibited synergism in various biochemical variables and also in DNA damage. Kidney total MT levels and genes expression of MT1, MT2, and proinflammatory cytokines were increased. All these changes were supported by histopathological observations. Co-exposure to aluminum and acrylamide exhibited synergism and more pronounced toxic effects compared with their individual effects based on various biochemical variables, genotoxic, and histopathological changes. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1044-1058, 2016. © 2015 Wiley Periodicals, Inc.

  4. Altered expression of nerve growth factor and its receptors in the kidneys of diabetic rats.

    PubMed

    Aloe, Luigi; Rossi, Simona; Manni, Luigi

    2011-01-01

    Type 1 diabetes (DB) is a multifactorial metabolic disorder characterized by loss of insulin-producing pancreatic ß-cells, and metabolic and functional deficits in a number of cells, including kidney cells. Nerve growth factor (NGF) is a signaling molecule that is up-regulated in cells affected by diabetes-linked disorders. However, whether DB alters the expression of NGF in the kidney is not known. DB was induced in adult male rats with a single injection of streptozotocin (STZ), and NGF protein levels were analyzed in a time-course study in serum and kidney. The expression of NGF receptors in the kidneys of healthy and DB rats was evaluated by immunohistochemistry. NGF levels as well as apoptotic features in the kidneys of healthy rats injected with purified NGF were also assessed. This study revealed that DB elevates NGF levels in serum and NGF expression in the kidney and that subcutaneous administration of NGF causes a marked uptake of NGF in kidney cells. The elevated presence of NGF in kidney cells is not associated with proapoptotic factor expression. The present data suggest that NGF presence in the kidney might play a survival, and most probably protective, role in kidney cells.

  5. Single adult kidney stem/progenitor cells reconstitute three-dimensional nephron structures in vitro.

    PubMed

    Kitamura, Shinji; Sakurai, Hiroyuki; Makino, Hirofumi

    2015-03-01

    The kidneys are formed during development from two distinct primordial tissues, the metanephric mesenchyme and the ureteric bud. The metanephric mesenchyme develops into the kidney nephron, the minimal functional unit of the kidney. A nephron consists of several segments and regulates water, electrolyte, and acid-base homeostasis in addition to secreting certain hormones. It has been predicted that the kidney will be among the last organs successfully regenerated in vitro due to its complex structure and multiple functions. Here, we show that adult kidney stem/progenitor cells (KS cells), derived from the S3 segment of adult rat kidney nephrons, can reconstitute a three-dimensional kidney-like structure in vitro. Kidney-like structures were formed when a cluster of KS cells was suspended in an extracellular matrix gel and cultured in the presence of several growth factors. Morphological analyses revealed that these kidney-like structures contained every substructure of the kidney, including glomeruli, proximal tubules, the loop of Henle, distal tubules, and collecting ducts, but no vasculature. Our results demonstrate that a cluster of tissue stem/progenitor cells has the ability to reconstitute the minimum unit of its organ of origin by differentiating into specialized cells in the correct location. This process differs from embryonic kidney development, which requires the mutual induction of two different populations of progenitors, metanephric mesenchymal cells and ureteric bud cells. © 2014 AlphaMed Press.

  6. A new apparatus for standardized rat kidney biopsy.

    PubMed

    Schirutschke, Holger; Gladrow, Lars; Norkus, Christian; Parmentier, Simon Paul; Hohenstein, Bernd; Hugo, Christian P M

    2014-01-01

    Survival biopsies are frequently applied in rat kidney disease models, but several drawbacks such as surgical kidney trauma, bleeding risk and variable loss of kidney tissue are still unsolved. Therefore, we developed an easy-to-use core biopsy instrument and evaluated whether two consecutive kidney biopsies within the same kidney can be carried out in a standardized manner. On day 0, 18 Lewis rats underwent a right nephrectomy and 9 of these rats a subsequent first biopsy of the left kidney (Bx group). 9 control rats had a sham biopsy of the left kidney (Ctrl group). On day 7, a second kidney biopsy/sham biopsy was performed. On day 42, all animals were sacrificed and their kidneys were removed for histology. Biopsy cylinders contained 57±28 glomeruli per transversal section, representing an adequate sample size. PAS staining showed that the biopsy depth was limited to the renal cortex whereas surgical tissue damage was limited to the area immediately adjacent to the taken biopsy cylinder. On day 42, the reduction of functional renal mass after two biopsies was only 5.2% and no differences of body weight, blood pressure, proteinuria, serum creatinine, glomerulosclerosis, interstitial fibrosis or number of ED-1 positive macrophages were found between both groups. In summary, our apparatus offers a safe method to perform repetitive kidney biopsies with minimal trauma and sufficient sample size and quality even in experimental disease models restricted to one single kidney.

  7. Identification and isolation of kidney-derived stem cells from transgenic rats with diphtheria toxin-induced kidney damage

    PubMed Central

    Liu, Qing-Zhen; Chen, Xu-Dong; Liu, Gang; Guan, Guang-Ju

    2016-01-01

    Adult stem cells have been well characterized in numerous organs, with the exception of the kidneys. Therefore, the present study aimed to identify and isolate kidney-derived stem cells. A total of 12 Fischer 344 transgenic rats expressing the human diphtheria toxin receptor in podocyte cells of the kidney, were used in the present study. The rats were administered 5-bromo-2′-deoxyuridine (BrdU) in order to detect cellular proliferation. After 60 days, the rats were treated with the diphtheria toxin (DT), in order to induce kidney injury. Immunohistochemical analysis indicated that the number of BrdU-positive cells were increased following DT treatment. In addition, the expression of octamer-binding transcription factor 4 (Oct-4), a stem cell marker, was detected and suggested that kidney-specific stem cells were present in the DT-treated tissue samples. Furthermore, tissue samples exhibited repair of the DT-induced injury. Further cellular culturing was conducted in order to isolate the kidney-specific stem cells. After 5 weeks of culture, the majority of the cells were non-viable, with the exception of certain specialized, unique cell types, which were monomorphic and spindle-shaped in appearance. The unique cells were isolated and subjected to immunostaining and reverse transcription-polymerase chain reaction analyses in order to reconfirm the expression of Oct-4 and to detect the expression of Paired box 2 (Pax-2), which is necessary for the formation of kidney structures. The unique cells were positive for Oct-4 and Pax-2; thus suggesting that the identified cells were kidney-derived stem cells. The results of the present study suggested that the unique cell type identified in the kidneys of the DT-treated rats were kidney-specific stem cells that may have been involved in the repair of DT-induced tissue injury. In addition, these cells may provide a useful cell line for studying the fundamental characteristics of kidney stem cells, as well as identifying

  8. The relationship between chemical-induced kidney weight increases and kidney histopathology in rats.

    PubMed

    Craig, Evisabel A; Yan, Zhongyu; Zhao, Q Jay

    2015-07-01

    The kidney is a major site of chemical excretion, which results in its propensity to exhibit chemically-induced toxicological effects at a higher rate than most other organs. Although the kidneys are often weighed in animal toxicity studies, the manner in which these kidney weight measurements are interpreted and the value of this information in predicting renal damage remains controversial. In this study we sought to determine whether a relationship exists between chemically-induced kidney weight changes and renal histopathological alterations. We also examined the relative utility of absolute and relative (kidney-to-body weight ratio) kidney weight in the prediction of renal toxicity. For this, data extracted from oral chemical exposure studies in rats performed by the National Toxicology Program were qualitatively and quantitatively evaluated. Our analysis showed a statistically significant correlation between absolute, but not relative, kidney weight and renal histopathology in chemically-treated rats. This positive correlation between absolute kidney weight and histopathology was observed even with compounds that statistically decreased terminal body weight. Also, changes in absolute kidney weight, which occurred at subchronic exposures, were able to predict the presence or absence of kidney histopathology at both subchronic and chronic exposures. Furthermore, most increases in absolute kidney weight reaching statistical significance (irrespective of the magnitude of change) were found to be relevant for the prediction of histopathological changes. Hence, our findings demonstrate that the evaluation of absolute kidney weight is a useful method for identifying potential renal toxicants. Copyright © 2014 John Wiley & Sons, Ltd.

  9. Kidney in potassium depletion. II. K/sup +/ handling by the isolated perfused rat kidney

    SciTech Connect

    Hayashi, M.; Katz, A.I.

    1987-03-01

    In a companion paper the authors reported a large increment in Na/sup +/-K/sup +/-ATPase activity and (/sup 3/H)ouabain binding the inner stripe of outer medullary collecting tubules from K-depleted rats. To test the hypothesis that the increased number of Na/sup +/-K/sup +/ pumps in these animals may be involved in potassium reabsorption they examined the effect of ouabain on K excretion by isolated, perfused kidneys from rats fed a K-free diet for 3 wk. Kidneys from K-depleted rats retain potassium avidly, both the fractional (FE/sub K/) and absolute K excretion being approximately fivefold lower than in control kidneys. Ouabain (5 mM) increased FE/sub K/ in kidneys from each K-depleted rat; similar results were obtained when kidneys were perfused with low and high potassium concentrations. In contrast, ouabain produced a variable effect in control kidneys, that depended on the perfusate potassium concentration. In K-depleted rats amiloride did not significantly alter K excretion and did not block the ouabain-induced kaliuresis, suggesting that the latter is not due to enhanced secretion secondary to increased distal fluid delivery. These results provide evidence for ouabain-sensitive potassium reabsorption in kidneys of chronically K-depleted rats, and suggest an explanation for the increased Na/sup +/-K/sup +/-ATPase observed in such animals.

  10. Exaggerated natriuresis in adult polycystic kidney disease.

    PubMed

    Danielsen, H; Nielsen, A H; Pedersen, E B; Herlevsen, P; Kornerup, H J; Posborg, V

    1986-01-01

    Angiotensin II (AII), aldosterone (Aldo) arginine vasopressin (AVP) in plasma, serum osmolality (Sosm), and renal sodium excretion (UNaV) were studied before and after infusion of hypertonic sodium chloride solution in 20 patients with adult polycystic kidney disease (PKD) with normal or moderately reduced creatinine clearance (Ccr) and in 10 healthy control subjects. UNaV increased after sodium loading in all, significantly more in the PKD patients. AII and Aldo were normal before sodium loading and suppressed after saline in PKD patients and controls. The increase in VNaV correlated with Aldo in patients but not in controls. AVP before loading was increased in hypertensive PKD patients with reduced Ccr, but not in normotensive patients with normal Ccr. After hypertonic saline, Sosm increased to the same degree both in PKD and control subjects, but AVP increased more in those with PKD. The exaggerated natriuresis of PKD is probably not explained by a change in the activity of the renin-angiotensin-aldosterone system. The enhanced response of AVP to osmotic stimuli in PKD may be a compensatory reaction to a reduced renal tubular effect of AVP.

  11. Nutrition for Early Chronic Kidney Disease in Adults

    MedlinePlus

    ... Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información de la ... Albumin in the Urine Managing CKD Eating Right Nutrition for Advanced Chronic Kidney Disease in Adults Preventing ...

  12. Oxidative stress induced by gibberellic acid on kidney tissue of female rats and their progeny: biochemical and histopathological studies.

    PubMed

    Troudi, Afef; Ben Amara, Ibtissem; Soudani, Nejla; Samet, Amira Mahjoubi; Zeghal, Najiba

    2011-09-01

    Gibberellic acid (GA(3)) is an endogenous plant growth regulator used worldwide in agriculture. The objective of this study was to investigate the effects of GA(3) on the kidney function of adult rats and their pups. Female Wistar rats were given daily 200 ppm GA(3) in drinking water from the 14th day of pregnancy until day 14 after delivery. GA(3) induced nephrotoxicity, as evidenced by a reduction in the 24-h urine volume and an increase in plasma creatinine, urea and uric acid levels. Nephrotoxicity was objectified by a significant increase of malondialdehyde level and a decrease of antioxidant enzyme activities like catalase, superoxide dismutase, glutathione peroxidase and glutathione content in kidneys of suckling pups and their mothers. Kidney histological studies confirmed biochemical parameters. We concluded that the exposure of rats to GA(3) induced oxidative stress and histopathological changes in kidneys of suckling rats and their mothers during late pregnancy and early postnatal periods.

  13. Effect of Nigella sativa on the kidney function in rats

    PubMed Central

    Dollah, Mohammad Aziz; Parhizkar, Saadat; Izwan, Mohammad

    2013-01-01

    Objectives: Nigella sativa (N. sativa) is an amazing herb which is used in traditional medicine for a wide range of illnesses including bronchial asthma, dysentery, gastrointestinal problems, as well as beneficial effect on blood lipids, lowering blood pressure, serum cholesterol, and triglycerides level. This study aimed to determine the toxic effect of N. sativa powder on the kidney function which was evaluated by serum urea and creatinine and through histopathological examination of kidney tissue. Methods and Materials: In this study, 24 male Sprague Dawley rats were randomly divided into four groups (six each). The rats were kept in the separate cage with three rats per cage. The treatment groups were given rat pellet containing N. sativa dose at 0.01, 0.10, and 1.00 g/kg body weight which were considered as low, normal, and high dose for five weeks while control group fed with rat chow pellet without supplementation. At the end of 35 days, the rats were sacrificed to take the blood sample and to remove the kidney organ for toxicity evaluation. Statistical analyses were done through one-way ANOVA using SPSS. Results: The finding revealed that there was no significant difference in serum urea of treatment groups compared with the control group. The results showed a significant decline in serum creatinine of high dose of Nigella sativa treated compared with low dose treated and control groups (p<0.05). Histopathological examination of kidney tissue showed normal kidney architecture with no tissue degeneration, inflammation, necrosis, and tubular dilation in all groups. Conclusion: With the evidence of normal urea and creatinine level in blood and normal kidney tissue in histology examination for all treatment groups, it is suggested that there is no toxic effect on kidney function of Nigella sativa at different doses for five-week period. PMID:25050269

  14. Mapping genetic determinants of kidney damage in rat models.

    PubMed

    Schulz, Angela; Kreutz, Reinhold

    2012-07-01

    During the last two decades, significant progress in our understanding of the development of kidney diseases has been achieved by unravelling the mechanisms underlying rare familial forms of human kidney diseases. Due to the genetic heterogeneity in human populations and the complex multifactorial pathogenesis of the disease phenotypes, the dissection of the genetic basis of common chronic kidney diseases (CKD) remains a difficult task. In this regard, several inbred rat models provide valuable complementary tools to uncover the genetic basis of complex renal disease phenotypes that are related to common forms of CKD. In this review, data obtained in nine experimental rat models, including the Buffalo (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki (GK), Lyon hypertensive (LH), Munich Wistar Frömter (MWF), Sabra hypertension-prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) inbred strains, that contributed to the genetic dissection of renal disease phenotypes are presented. In this panel of inbred strains, a large number of quantitative trait loci (QTL) linked to albuminuria/proteinuria and other functional or structural kidney abnormalities could be identified by QTL mapping analysis and follow-up studies including consomic and congenic rat lines. The comprehensive exploitation of the genotype-renal phenotype associations that are inherited in this panel of rat strains is suitable for making a significant contribution to the development of an integrated approach to the systems genetics of common CKD.

  15. Cellular localization of aquaporin 7 in the rat kidney.

    PubMed

    Ishibashi, K; Imai, M; Sasaki, S

    2000-01-01

    The cDNA for the seventh mammalian aquaporin (AQP7) was isolated from rat testis, and its expression was demonstrated at the tail of late spermatids [Ishibashi et al: J Biol Chem 1997;272:20782-20786]. AQP7 is also expressed in the kidney. The localization of AQP7 in the kidney is unknown. We examined the cellular localization of AQP7 in the kidney with Northern blot, reverse transcribed PCR, Western blot and immunohistochemistry in the rat kidney. In Northern blot, AQP7 was expressed in the cortex and the outer medulla but absent in the inner medulla of the kidney. Reverse transcribed PCR of rat nephron segments revealed the selective expression of AQP7 at the proximal straight tubules (PST). Western blot of the membrane fraction of outer medulla revealed a single band of approximately 33 kDa. Immunohistochemistry of the rat kidney showed the selective expression of AQP7 at the brush border membranes of PST (S3 segment). AQP7 is now shown to be localized selectively at the brush border membranes of PST in the rat kidney. The result suggests that AQP7 may function as a pathway for transcellular water transport in PST in concert with more widely expressed AQP1 in proximal tubules. Alternatively, as AQP7 transports urea as well as water, AQP7 may function as a passive urea secretory pathway in this segment and may play a role in the formation and/or maintenance of the medullary urea concentration gradient. Copyright 2000 S. Karger AG, Basel

  16. Morphological Characteristics of Renal Artery and Kidney in Rats

    PubMed Central

    Yoldas, Atilla; Dayan, Mustafa Orhun

    2014-01-01

    The gross anatomy and morphometry of the kidney and renal arteries were studied in the strains of laboratory rat: Sprague-Dawley (Sp) and Wistar (W) rats. Total of 106 three-dimensional endocasts of the intrarenal arteries of kidney that were prepared using standard injection-corrosion techniques were examined. A single renal artery was observed in 100% of the cases. The renal arteries were divided into a dorsal and a ventral branch. The dorsal and ventral branches were divided into two branches, the cranial and caudal branch. Renal arteries were classified into types I and II, depending on the cranial and caudal branches and their made of branching. The present study also showed that the right kidney was slightly heavier than the left one and that the kidney of the male was generally larger than that of the female. The mean live weights of the Sprague-Dawley and Wistar rats were found to be 258.26 ± 5.9 and 182.4 ± 19.05 g, respectively. The kidney weights were significantly correlated (P < 0.01) with body weights. The kidney weights were not found significantly correlated (P > 0.01) with the length of renal arteries. PMID:24737971

  17. Beta-adrenoceptors in kidney tubules of spontaneously hypertensive and normotensive rats

    SciTech Connect

    Struyker-Boudier, H.A.J.; Vervoort-Peters, L.H.T.M.; Rousch, M.J.M.; Smits, J.F.M.; Thijssen, H.H.W.

    1986-01-13

    Beta-adrenoceptor binding characteristics were determined in different fractions of rat kidney tubules using a (/sup 125/Iodo)-(-)-cyanopindolol (ICYP) binding assay. The highest amount of binding sites was found in a fraction containing predominantly distal tubular fragments. In a separate series of experiments the ICYP binding characteristics were compared in whole tubular fractions from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) of different ages. The maximum number of binding sites was significantly higher both in young (3 weeks) and adult (14 weeks) SHR when compared to age-matched WKY. These studies showed the presence of beta-adrenoceptor binding sites in rat kidney tubules and support the potential importance of tubular beta-adrenoceptors in the development of spontaneous hypertension and in the mechanism of antihypertensive action of beta-blockers. 35 references, 1 figure, 3 tables.

  18. Histopathology of kidney of albino rat poisoned with uranyl nitrate

    SciTech Connect

    Goel, K.A.; Garg, V.K.; Garg, V.

    1980-01-01

    Heavy metals input into the media either terrestrial or aquatic is an important aspect of environmental pollution. Heavy metals are known to produce toxic effects on the different tissues of various terrestrial and aquatic animals. Some of these are highly toxic at even very low concentrations and they alter the cellular architecture of many organs including the kidney. Little has been done on the effect of rare earth metals, particularly that of uranium on the kidney of animals. In the present paper histopathological changes produced by uranium on the kidney of albino rats are discussed.

  19. Ursolic Acid provides kidney protection in diabetic rats.

    PubMed

    Ling, Chen; Jinping, Lu; Xia, Li; Renyong, Yang

    2013-12-01

    Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and the leading cause of end-stage renal failure. However, the treatment of DN is still a problem in the world. Inflammatory process plays a critical role in the development of DN. Therefore, anti-inflammatory treatment of DN is worth exploring now and in the future. The study aimed to evaluate the impact of ursolic acid (UA) on renal function in streptozotocin-induced diabetes. Rats with streptozotocin-induced diabetes were treated with UA for 16 weeks. After 16 weeks, urine albumin excretion, serum creatinine, and blood urea nitrogen were measured. In addition, renal oxidative stress level, nuclear factor kappa-B (NF-κB) activity, P-selectin expression, and kidney histopathologic changes were evaluated. Sixteen weeks following streptozotocin injection, the rats produced significant alteration in renal function and increased oxidative stress, NF-κB activity, and P-selectin expression in the kidneys. Interestingly, UA significantly prevented biochemical and histopathologic changes in the kidneys associated with diabetes. Compared with untreated diabetic rats, UA treatment lowered urine albumin excretion, renal oxidative stress level, NF-κB activity, and P-selectin expression. Moreover, UA treatment also improved renal histopathologic changes in rats with diabetes. UA treatment exhibited a protective effect on kidneys in diabetic rats, implying that UA could be a potential treatment for diabetic nephropathy.

  20. ARISTOLOCHIC ACID I METABOLISM IN THE ISOLATED PERFUSED RAT KIDNEY

    PubMed Central

    Priestap, Horacio A.; Torres, M. Cecilia; Rieger, Robert A.; Dickman, Kathleen G.; Freshwater, Tomoko; Taft, David R.; Barbieri, Manuel A.; Iden, Charles R.

    2012-01-01

    Aristolochic acids are natural nitro-compounds found globally in the plant genus Aristolochia that have been implicated in the severe illness in humans termed aristolochic acid nephropathy (AAN). Aristolochic acids undergo nitroreduction, among other metabolic reactions, and active intermediates arise that are carcinogenic. Previous experiments with rats showed that aristolochic acid I (AA-I), after oral administration or injection, is subjected to detoxication reactions to give aristolochic acid Ia, aristolactam Ia, aristolactam I and their glucuronide and sulfate conjugates that can be found in urine and faeces. Results obtained with whole rats do not clearly define the role of liver and kidney in such metabolic transformation. In this study, in order to determine the specific role of the kidney on the renal disposition of AA-I and to study the biotransformations suffered by AA-I in this organ, isolated kidneys of rats were perfused with AA-I. AA-I and metabolite concentrations were determined in perfusates and urines using HPLC procedures. The isolated perfused rat kidney model showed that AA-I distributes rapidly and extensively in kidney tissues by uptake from the peritubular capillaries and the tubules. It was also established that the kidney is able to metabolize AA-I into aristolochic acid Ia, aristolochic acid Ia O-sulfate, aristolactam Ia, aristolactam I and aristolactam Ia O-glucuronide. Rapid demethylation and sulfation of AA-I in the kidney generate aristolochic acid Ia and its sulfate conjugate that are voided to the urine. Reduction reactions to give the aristolactam metabolites occur to a slower rate. Renal clearances showed that filtered AA-I is reabsorbed at the tubules whereas the metabolites are secreted. The unconjugated metabolites produced in the renal tissues are transported to both urine and perfusate whereas the conjugated metabolites are almost exclusively secreted to the urine. PMID:22118289

  1. Effect of maturation and aging on beta-adrenergic signal transduction in rat kidney and liver.

    PubMed

    Fraeyman, N; Van de Velde, E; Van Ermen, A; Bazan, A; Vanderheyden, P; Van Emmelo, J; Vandekerckhove, J

    2000-12-15

    The characteristics of the beta-adrenergic signal transduction system were analyzed in kidney and liver membrane preparations from neonatal (2-3 days), mature (2 months), and old (2 years) rats. When comparing kidneys from adult to neonatal rats, we found a higher beta-receptor density and a higher percentage of beta(1)-receptor subtype, lower immunoreactive G(salpha)-protein, a lower ratio between the high and low molecular weight splice variant of G(salpha), lower immunoreactive G(ialpha)-protein, and lower basal adenylate cyclase activity. When comparing livers from adult to neonatal rats, we found lower beta-receptor density and basal adenylate cyclase activity. Very few differences could be detected when comparing mature to old kidneys or livers. Stimulated adenosine 3',5'-cyclic monophosphate (cAMP) synthesis was tissue- and age-dependent. In liver, G-protein- and beta-receptor-stimulated cAMP synthesis mirrored basal adenylate cyclase activity and was highest in liver from neonatal animals. In contrast, cAMP synthesis was significantly more stimulated in kidneys from mature animals than from neonatal and senescent rats. We conclude that: (i) the stoichiometry of the components within the beta-receptor/G-protein/adenylate cyclase complex is not fixed but is both tissue- and age-dependent; (ii) adenylate cyclase enzyme activity is possibly but not necessarily the rate-limiting step in the beta-receptor-mediated synthesis of cAMP; and (iii) there is in vivo evidence for a preferential co-expression of the large splice variant of the G(s)-protein and beta(2)-receptor subtype. It is speculated that this could have important physiological consequences for the development of the kidney.

  2. Acute mercury exposition of virgin, pregnant, and lactating rats: Histopathological kidney and liver evaluations.

    PubMed

    Oliveira, Vitor Antunes; Favero, Gaia; Stacchiotti, Alessandra; Giugno, Lorena; Buffoli, Barbara; de Oliveira, Claudia Sirlene; Lavazza, Antonio; Albanese, Massimo; Rodella, Luigi Fabrizio; Pereira, Maria Ester; Rezzani, Rita

    2017-05-01

    This work investigated the effects of mercury chloride (HgCl2 ) acute exposure on virgin, pregnant and lactating rats by determination of renal and hepatic morphological and ultrastructural parameters and the expression of oxidative stress and stress tolerance markers, due to kidney and liver are the organs that more accumulate inorganic mercury. Adult Wistar rats virgin (90 days old), pregnant (18(th) gestation day) and lactating (7(th) lactation day) were injected once with HgCl2 (5 mg/kg) or saline (controls). We observed that HgCl2 exposure of virgin rats caused significant inflammatory infiltration and severe morphological variations, like glomeruli atrophy, dilatation of Bowman's capsule, tubular degeneration and hepatocytes alteration. Moreover, virgin rats presented mitochondrial modification, important oxidative stress and increase in stress tolerance proteins at both kidney and liver level, compared with virgin controls. In detail, virgin rats exposed to HgCl2 presented significantly elevated level of inducible nitric oxide synthase, heat shock protein 27 and glucose regulated proteins 75 expressions at both renal tubular and hepatocytes level, respect untreated virgin rats. Interestingly, pregnant and lactating rats exposed to HgCl2 presented weak renal and liver morphological alterations, showing weak inflammatory infiltration and no significant difference in structural mitochondrial transmembrane protein, oxidative stress markers and stress tolerance proteins expressions respect controls (virgin, pregnant and lactating rats). Although, both control and HgCl2 -exposed pregnant and lactating rats showed renal glomeruli greater in diameter respect virgin rats. In conclusion, we believe that virgin rats are more sensitive to HgCl2 toxicity respect pregnant and lactating rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1500-1512, 2017. © 2016 Wiley Periodicals, Inc.

  3. Trends in Kidney Transplant Outcomes in Older Adults Running Header: Kidney Transplant Outcomes in Older Adults

    PubMed Central

    McAdams-DeMarco, Mara A.; James, Nathan; Salter, Megan L.; Walston, Jeremy; Segev, Dorry L.

    2015-01-01

    Objectives Age limits for kidney transplantation (KT) have expanded significantly in recent years, yet outcomes in older recipients remain poorly understood. The goal of this study was to estimate relative mortality and death-censored graft loss by year of KT between 1990–2011. Design Cohort study. Setting All KT recipients in the United States as reported to the Scientific Registry of Transplant Recipients (SRTR). Participants 30,207 KT recipients aged ≥65 at the time of transplantation. Measurements Mortality and death-censored graft loss ascertained through center report, linkage to Social Security Death Master File, and linkage to Medicare. Results Older adults currently represent 18.4% of KT recipients, a 5-fold rise from 3.4% in 1990; similar increases were noted for both deceased (5.4-fold) and live donor (9.1-fold) transplants. Current recipients are not only older, but also more likely to be female, African American, have lengthier pre-transplant dialysis, have diabetes or hypertension, and receive marginal kidneys. Mortality for older deceased donor recipients between 2009–2011 was 57% lower (HR=0.43, 95%CI:0.33–0.56, P<0.001) than in 1990–1993; mortality for older live donor recipients was 50% lower (HR=0.50, 95%CI:0.36–0.68, P<0.001). Death-censored graft loss for older deceased donor recipients between 2009–2011 was 65% lower (HR=0.35, 95% CI:0.29–0.42, P<0.001) than in 1990–1993; death-censored graft loss for older live donor KT recipients was 59% lower (HR=0.41, 95%CI:0.24–0.70, P<0.001). Conclusion Despite a major increase in number of older adults transplanted, and an expanding window of transplant eligibility, mortality and graft loss have decreased substantially for this recipient population. These trends are important to understand, both for patient counseling as well as transplant referral. PMID:25439325

  4. Adult Human CD133/1+ Kidney Cells Isolated from Papilla Integrate into Developing Kidney Tubules

    PubMed Central

    Ward, Heather H.; Romero, Elsa; Welford, Angela; Pickett, Gavin; Bacallao, Robert; Gattone, Vincent H.; Ness, Scott A.; Wandinger-Ness, Angela; Roitbak, Tamara

    2011-01-01

    Approximately 60,000 patients in the US are waiting for a kidney transplant due to genetic, immunologic and environmentally caused kidney failure. Adult human renal stem cells could offer opportunities for autologous transplant and repair of damaged organs. Current data suggest that there are multiple progenitor types in the kidney with distinct localizations. In the present study, we characterize cells derived from human kidney papilla and show their capacity for tubulogenesis. In situ, nestin+ and CD133/1+ cells were found extensively intercalated between tubular epithelia in the loops of Henle of renal papilla, but not of the cortex. Populations of primary cells from the renal cortex and renal papilla were isolated by enzymatic digestion from human kidneys unsuited for transplant and immuno-enriched for CD133/1+ cells. Isolated CD133/1+ papillary cells were positive for nestin, as well as several human embryonic stem cell markers (SSEA4, Nanog, SOX2, and OCT4/POU5F1) and could be triggered to adopt tubular epithelial and neuronal like phenotypes. Isolated papillary cells exhibited morphologic plasticity upon modulation of culture conditions and inhibition of asymmetric cell division. Labeled papillary cells readily associated with cortical tubular epithelia in co-culture and 3-dimensional collagen gel cultures. Heterologous organ culture demonstrated that CD133/1+ progenitors from the papilla and cortex, became integrated into developing kidney tubules. Tubular epithelia did not participate in tubulogenesis. Human renal papilla harbor cells with the hallmarks of adult kidney stem/progenitor cells that can be amplified and phenotypically modulated in culture while retaining the capacity to form new kidney tubules. PMID:21255643

  5. Decellularization of Rat Kidneys to Produce Extracellular Matrix Scaffolds.

    PubMed

    Jin, Mei; Yaling, Yu; Zhibin, Wang; Jianse, Zhang

    2016-01-01

    The extracellular matrix (ECM) retains three-dimensional structures for the stimulation of cell growth, with components of the ECM relatively conserved between species. Interest in the use of decellularized scaffold-based strategies for organ regeneration is increasing rapidly. Decellularized scaffolds derived from animal organs are a promising material for organ engineering, with a number of prominent advances having been reported in the past few years.In this article we describe a simple and robust methodology for generating decellularized rat kidneys. To obtain these scaffolds, we perfuse rat kidneys with detergents through the abdominal aorta. After decellularization, kidney scaffolds are harvested for evaluation of vascular structure and histology. Qualitative evaluation involves vascular corrosion casting, transmission electron microscopy, and several different histological and immunofluorescent methods. SDS residue levels are assessed by ultraviolet-visible spectrophotometer (UV-VIS).

  6. THE EFFECT OF TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT LONG-EVANS (EKER) RATS.

    EPA Science Inventory

    The effect of a targeted knockout mutation on the transcriptional profile of the kidney in
    Tsc2 mutant Long-Evans (Eker) rats.

    Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting
    for up to 80% of malignant renal neoplasms. Hereditary...

  7. THE EFFECT OF TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT LONG-EVANS (EKER) RATS.

    EPA Science Inventory

    The effect of a targeted knockout mutation on the transcriptional profile of the kidney in
    Tsc2 mutant Long-Evans (Eker) rats.

    Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting
    for up to 80% of malignant renal neoplasms. Hereditary...

  8. A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats.

    PubMed

    Tanvir, E M; Afroz, R; Chowdhury, Maz; Gan, S H; Karim, N; Islam, M N; Khalil, M I

    2016-09-01

    This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.

  9. Inhalation of mercury vapor can cause the toxic effects on rat kidney.

    PubMed

    Akgül, Nilgün; Altunkaynak, Berrin Zuhal; Altunkaynak, Muhammed Eyüp; Deniz, Ömür Gülsüm; Ünal, Deniz; Akgül, Hayati Murat

    2016-01-01

    Dental amalgam has been used in dentistry as a filling material. The filler comprises mercury (Hg). It is considered one of the most important and widespread environmental pollutants, which poses a serious potential threat for the humans and animals. However, mercury deposition affects the nervous, cardiovascular, pulmonary, gastrointestinal, and especially renal systems. In most animals' species and humans, the kidney is one of the main sites of deposition of mercury and target organ for its toxicity. In this study, the effects of mercury intake on kidney in rats were searched. For the this purpose; we used 24 adult female Wistar albino rats (200 g in weight) obtained from Experimental Research and Application Center of Atatürk University with ethical approval. Besides, they were placed into a specially designed glass cage. Along this experiment for 45 days, subjects were exposed to (1 mg/m(3)/day) mercury vapor. However, no application was used for the control subjects. At the end of the experiment, kidney samples were obtained from all subjects and processed for routine light microscopic level and stereological aspect were assessed. Finally, according to our results, mercury affects the histological features of the kidney. That means, the severe effects of mercury has been shown using stereological approach, which is one of the ideal quantitative methods in the current literature. In this study, it was detected that chronic exposure to mercury vapor may lead to renal damage and diseases in an experimental rat model.

  10. THE EFFECT OF A TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT (EKER) RATS.

    EPA Science Inventory

    Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting for up to 80% of malignant renal neoplasms. Hereditary RCC in the Eker rat, which bear a number of cellular, molecular and phenotypic similarities to human RCC, results from an inherited insertion...

  11. THE EFFECT OF A TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT (EKER) RATS.

    EPA Science Inventory

    Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting for up to 80% of malignant renal neoplasms. Hereditary RCC in the Eker rat, which bear a number of cellular, molecular and phenotypic similarities to human RCC, results from an inherited insertion...

  12. Uric acid metabolism of kidney and intestine in a rat model of chronic kidney disease.

    PubMed

    Nagura, Michito; Tamura, Yoshifuru; Kumagai, Takanori; Hosoyamada, Makoto; Uchida, Shunya

    2016-12-01

    Uric acid (UA) is a potential risk factor of the progression of chronic kidney disease (CKD). Recently, we reported that intestinal UA excretion might be enhanced via upregulation of the ATP-binding cassette transporter G2 (Abcg2) in a 5/6 nephrectomy (Nx) rat model. In the present study, we examined the mRNA and protein expressions of UA transporters, URAT1, GLUT9/URATv1, ABCG2 and NPT4 in the kidney and ileum in the same rat model. Additionally, we investigated the Abcg2 mRNA expression of ileum in hyperuricemic rat model by orally administering oxonic acid. Male Wistar rats were randomly assigned to three groups consisting of Nx group, oxonic acid-treated (Ox) group and sham-operated control group, and sacrificed at 8 weeks. Creatinine and UA were measured and the mRNA expressions of UA transporters in the kidney and intestine were evaluated by a real time PCR. UA transporters in the kidney sections were also examined by immunohistochemistry. Serum creatinine elevated in the Nx group whereas serum UA increased in the Ox group. Both the mRNA expression and the immunohistochemistry of the UA transporters were decreased in the Nx group, suggesting a marginal role in UA elevation in decreased kidney function. In contrast, the mRNA expression of Abcg2 in the ileum significantly increased in the Ox group. These results suggest that the upregulation of Abcg2 mRNA in the ileum triggered by an elevation of serum UA may play a compensatory role in increasing intestinal UA excretion.

  13. Approach to the Adult Kidney Stone Former

    PubMed Central

    Maalouf, Naim

    2012-01-01

    Nephrolithiasis is a prevalent and costly condition with high recurrence rate. A medical evaluation to identify abnormalities responsible for nephrolithiasis and guide subsequent therapy has been advocated to reduce the risk of stone recurrence. The evaluation of kidney stone formers generally comprises an extensive medical history to identify metabolic, environmental, dietary and/or genetic factors contributing to stone formation. Imaging studies are utilized to evaluate and follow stone burden. Laboratory studies including stone composition analysis and serum and urinary chemistries are commonly obtained to further assess for any underlying systemic disorders, to detect environmental and metabolic processes contributing to stone disease, and to guide initial and follow-up dietary and pharmacological therapy. The nature and extent of such an evaluation is discussed in this review article. PMID:22654574

  14. Nicotine withdrawal in adolescent and adult rats.

    PubMed

    O'Dell, Laura E; Bruijnzeel, Adrie W; Ghozland, Sandy; Markou, Athina; Koob, George F

    2004-06-01

    Previous research with animal models has demonstrated that adolescent rats display heightened sensitivity to the reinforcing and stimulant effects of nicotine relative to adult rats. Little work has focused on the response of adolescent rats to measures of nicotine withdrawal. To test the hypothesis that adolescent rats may be differentially sensitive to withdrawal relative to their adult counterparts, the present study was designed to compare precipitated withdrawal in adolescent and adult rats following chronic nicotine administration. Adult and adolescent rats were prepared with subcutaneous osmotic minipumps that delivered either saline or nicotine (9 mg/kg per day, salt; N =12 per group). All rats were challenged with the nicotinic receptor antagonist mecamylamine (1.5 mg/kg) on day 7 of chronic nicotine treatment. Twenty minutes after the injection, overt somatic signs of withdrawal (i.e., eye blinks, writhes, body shakes, teeth chatter, gasps, and ptosis) were recorded for 10 min. Adult rats were observed on postnatal day 73-77, and adolescent rats were tested on postnatal day 36-40. The results revealed a robust increase in mecamylamine-induced withdrawal signs in adult rats receiving chronic nicotine relative to adult rats receiving saline. In contrast, mecamylamine did not precipitate withdrawal signs in adolescent rats receiving chronic nicotine. These results indicate that there is decreased sensitivity to the somatic aspects of nicotine withdrawal in adolescent rats that may maximize the reinforcing effects of nicotine during adolescence by minimizing the aversive effects of abstinence.

  15. Lutein protects against ischemia/reperfusion injury in rat kidneys.

    PubMed

    Liu, Zhen-Guo; Qi, Zong-Cai; Liu, Wei-Liang; Wang, Wei-Zhi

    2015-03-01

    Ischemia‑reperfusion (I/R) injury has a major impact on renal dysfunction during transplantation. The present study investigated the role of lutein against I/R injury‑induced oxidative stress in rat kidneys. Biochemical analysis and oxidative stress parameters demonstrated that lutein protected the rat kidney significantly from I/R injury. Pretreatment with lutein significantly increased the total antioxidant capacity with a concomitant decline in the total oxidant status. Rats with I/R injury showed a significant increase in oxidative stress. The results revealed significant increases in the levels of lipid peroxidation and protein carbonyl content with concomitant decreases in enzymic and non‑enzymic antioxidants. The activity of these enzymes was reversed and demonstrated a significant increase following lutein pre‑treatment compared with the rats subjected to I/R injury alone. Furthermore, lutein protected the renal tissue from I/R injury by maintaining normal kidney architecture and led to a reduction in the levels of the renal markers urea and creatinine in the serum. These results demonstrated clear evidence that lutein offered a significant protective effect against I/R injury by enhancing antioxidant defense mechanisms.

  16. RT-PCR-based evidence for the in vivo stimulation of renal tubularp-aminohippurate (PAH) transport by triiodothyronine (T3) or dexamethasone (DEXA) in kidney tissue of immature and adult rats.

    PubMed

    Bahn, Andrew; Hauss, Achim; Appenroth, Dorothea; Ebbinghaus, Diana; Hagos, Yohannes; Steinmetzer, Peter; Burckhardt, Gerhard; Fleck, Christian

    2003-06-01

    Our previous studies have shown that a pre-treatment of rats with triiodothyronine (T3) or dexamethasone (DEXA) increases renal PAH excretion significantly. This stimulation was accompanied by an enhanced protein synthesis within the renal cortex. To explore the molecular basis for this sub-chronic induction process, we investigated the stimulation of PAH accumulation in renal cortical slices as well as the expression level of organic anion transporter 1 (OAT1), the recently cloned renal basolateral PAH-transporter, using RT-PCR techniques under the applied conditions. 10- and 55-day-old Han:WIST rats were treated in vivo with T3 (20 microg/100 g b.wt.) or DEXA (60 microg/100 g b.wt.), both for 3 days, once daily. Renal cortical slices were incubated for 2 hours in Cross-Taggart medium and PAH uptake into kidney tissue was measured time dependently (slice to medium ratio, QS/M). The accumulation capacity is comparable between immature and mature rats (control-QS/M: 6.7 +/- 0.1 vs. 6.9 +/- 0.2, respectively). Both age groups showed a significant increase of PAH accumulation capacity after T3 treatment (10-day-old rats: 15.0 +/- 0.2; 55-day-old rats: 11.7 +/- 1.3). After DEXA pre-treatment, PAH accumulation was only slightly changed (10-day-old rats: 5.9 +/- 0.2; 55-day-old rats: 8.2 +/- 1.3). Semi-quantitative measurements of OAT1 mRNA expression level showed a significant increase of OAT1 mRNA after pre-treatment with both T3 and DEXA in the two age groups. Thus, this is the first evidence that T3 and DEXA pre-treatment induces the expression of OAT1.

  17. Kidney dysfunction and silent brain infarction in generally healthy adults.

    PubMed

    Kim, Sang Hyuck; Shin, Dong Wook; Yun, Jae Moon; Lee, Ji Eun; Lim, Jae-Sung; Cho, Be Long; Kwon, Hyung-Min; Park, Jin-Ho

    2017-08-15

    The association between silent brain infarction (SBI) and estimated glomerular filtration rate (eGFR)-based kidney dysfunction has not yet been definitively confirmed. This study aimed to investigate the association in generally healthy adults without a previous history of stroke or overt kidney disease. The data from the screening health check-up program in the Seoul National University Hospital Health Promotion Center from January 1, 2009 to December 31, 2013 were used. A total of 2594 subjects who underwent brain MRI as part of health screening were included. SBIs were identified using T2-weighted and FLAIR images. Kidney dysfunction was defined as eGFR<60ml/min/1.73m(2). To assess the effect of kidney dysfunction on the small perforating branches of cerebral vessels, subgroup analysis was performed using the presence of SLI as a dependent variable. The mean age was 56.8±9.3years, and 1422 subjects (54.8%) were male. The mean eGFR level was 81.9±15.4ml/min/1.73m(2). The prevalence rates of kidney dysfunction and SBI were 5.1% and 7.1%, respectively. A higher proportion of subjects with SBI had kidney dysfunction than subjects without SBI (14.6% vs. 4.4%). The number of SBI lesions tended to increase with the progression of kidney dysfunction (p for trend<0.001). In multivariate logistic regression analyses, kidney dysfunction was significantly associated with the presence of SBI (adjusted odd ratio=1.99 to 2.21 in all four models). The same significant association was consistently identified in subgroup analyses using silent lacunar infarction (adjusted odd ratio=1.71 to 1.87 in all four models). Kidney dysfunction was found to be an independent risk factor for the presence and number of SBI in generally healthy adults. Physicians treating patients with a decreased creatinine-based eGFR level should try to identify and modify the coexisting risk factors of stroke followed by SBI. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Kidney transplantation in the older adult.

    PubMed

    Knoll, Greg A

    2013-05-01

    The end-stage renal disease population is aging. Nearly half of all new patients are older than 65 years and one third are older than 70 years. Assessing the possibility of transplantation for older patients with end-stage renal disease often involves contemplating more complex issues, including cognitive impairment, decreased functional status, and frailty, which makes selecting appropriate candidates more difficult. Older transplant recipients have decreased patient and transplant survival compared with younger recipients. For example, 75% of deceased donor transplant recipients aged 30-49 years are alive after 5 years compared to only 61% for those older than 65 years. Despite poorer outcomes compared with younger recipients, older transplant recipients have a significant improvement in survival compared with similar patients who remain on the wait list, with decreases in mortality of 41%-61% depending on the study. Use of living donors, even older living donors, provides significantly better outcomes for elderly recipients compared with the use of deceased donors. However, in the absence of a living donor, survival is improved significantly by accepting an expanded criteria donor organ rather than waiting for a standard criteria deceased donor. Older transplant recipients experience more infectious complications and less acute rejection, but the risk of transplant loss from rejection is increased compared with younger patients. These immunologic issues, along with the fact that older patients often are excluded from transplant trials, have made selecting an ideal immunosuppressive regimen challenging. Prospective comparative trials of different agents in the elderly population are warranted to better define the risk-benefit profile. This review discusses transplantation outcomes, including patient and transplant survival, different donor types, quality of life, and immunosuppression for older dialysis patients. Copyright © 2013 National Kidney Foundation, Inc

  19. Determination of boron distribution in rat's brain, kidney and liver.

    PubMed

    Pazirandeh, Ali; Jameie, Behnam; Zargar, Maysam

    2009-07-01

    To determine relative boron distribution in rat's brain, liver and kidney, a mixture of boric acid and borax, was used. After transcardial injection of the solution, the animals were sacrificed and the brain, kidney and liver were removed. The coronal sections of certain areas of the brain were prepared by freezing microtome. The slices were sandwiched within two pieces of CR-39. The samples were bombarded in a thermal neutron field of the TRR pneumatic facility. The alpha tracks are registered on CR-39 after being etched in NaOH. The boron distribution was determined by counting these alpha tracks CR-39 plastics. The distribution showed non-uniformity in brain, liver and kidney.

  20. Glomerulocystic kidney disease in an adult with enlarged kidneys: a case report and review of the literature.

    PubMed

    Obata, Y; Furusu, A; Miyazaki, M; Nishino, T; Kawazu, T; Kanamoto, Y; Nishikido, M; Taguchi, T; Kohno, S

    2011-02-01

    We report the case of a 31-year-old male with enlarged kidneys and glomerulocystic kidney disease (GCKD). The patient had no family history of renal disease or other diseases. On initial presentation he complained of poor eyesight, and hypertensive retinopathy and elevated serum creatinine (5.0 mg/dl) were found at that time. Renal biopsy showed cystic dilatation of Bowman's capsule and atrophy of the glomerular tuft. Thus, an adult case of sporadic GCKD was diagnosed. Based on previous reports, kidney size in patients with adult type GCKD varies from small to large. Our patient's kidneys are the largest ever reported (right kidney was 22 cm×10 cm, left kidney was 19 cm×10 cm). A review of the literature dealing with sporadic adult GCKD suggested that it is difficult to diagnose this disease early in its course.

  1. Apoptosis of rat kidney cells after 241-americium administration.

    PubMed

    Labéjof, L; Berry, J P; Duchambon, P; Poncy, J L; Galle, P

    1998-01-01

    Tumors induction by americium is well known but there are no data on the biological effects of this radionucleide at subcellular level. In order to study the possible ultrastructural lesions induced by this element, a group of rats were injected with 241-Americium-citrate (9 kBq), once a week for five weeks and sacrificed 7 days after the last injection. We describe the alterations observed in the cortex kidney using cytochemical (TUNEL reaction) and histochemical (PAS staining) methods for light microscopy as well as electron microscopy techniques. Various types of lesions were detected: condensation of nuclear chromatine, fragmentation of the nuclei, swollen mitochondria, disappearance of mitochondrial crests and skrinking of the cytoplasm. This study clearly demonstrated the induction of apoptosis by americium in rat cortex kidney cells.

  2. Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats.

    PubMed

    Rajeh, Nisreen A; Al-Dhaheri, Najlaa M

    2017-02-01

    To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone). After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out.  Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats.  Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E.

  3. Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats

    PubMed Central

    Rajeh, Nisreen A.; Al-Dhaheri, Najlaa M.

    2017-01-01

    Objectives: To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone). After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out. Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats. Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E PMID:28133684

  4. [Uncaria tomentosa and acute ischemic kidney injury in rats].

    PubMed

    de Fátima Fernandes Vattimo, Maria; da Silva, Natalia Oliveira

    2011-03-01

    The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat's claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities.

  5. Congenital hepatic fibrosis, liver cell carcinoma and adult polycystic kidneys.

    PubMed

    Manes, J L; Kissane, J M; Valdes, A J

    1977-06-01

    In reviewing the literature, we found no liver cell carcinoma (LCC) or well-documented adult polycystic kidneys (APK) associated with congenital hepatic fibrosis (CHF). We report a 69-year-old man with CHF, LCC, APK, duplication cyst of distal portion of stomach, two calcified splenic artery aneurysms, myocardial fibrosis and muscular hypertrophy of esophagus. The LCC was grossly predunculated and microscopically showed prominent fibrosis and hyaline intracytoplasmic inclusions in the tumor cells.

  6. Selenium-containing proteins of rat kidney and liver microsomes

    SciTech Connect

    Viljoen, A.J.; Motchnik, P.A.; Tappel, A.L. )

    1989-12-01

    Selenium (Se)-containing proteins in microsomal fractions of rat kidney and liver were investigated after isotopic labeling of rats with ({sup 75}Se)selenite. More than 85% of the {sup 75}Se in the solubilized microsomal extracts precipitated with protein after trichloroacetic acid treatment. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), used to separate the labeled protein subunits in the solubilized microsomal extracts, revealed several {sup 75}Se-containing proteins in addition to glutathione peroxidase. {sup 75}Se-labeled subunits with molecular weights of 55, 30, 26, 22, 19, and 17 kDa were present in microsomal fractions of kidney and liver. The {sup 75}Se-labeled tryptic peptide of the 55 kDa subunit had the same Rf value on a 17% SDS-PAGE gel as the peptide from plasma selenoprotein P. A time-course study of the labeling of individual protein subunits in kidney and liver microsomes from Se-supplemented and Se-deficient rats showed that most of the {sup 75}Se was associated with the 55 kDa subunit 3 hr after injection. The amount of {sup 75}Se associated with this protein subunit decreased by 12 hr, with a concurrent increase in the labeling of lower molecular-weight subunits. The results support the hypothesis that there is a mechanism for transfer of Se from the 55 kDa subunit to other Se-containing proteins.

  7. The Toxicity of Aluminum Chloride on Kidney of Rats.

    PubMed

    Liu, Jianyu; Wang, Qin; Sun, Xudong; Yang, Xu; Zhuang, Cuicui; Xu, Feibo; Cao, Zheng; Li, Yanfei

    2016-10-01

    This study investigated the toxicity of aluminum chloride (AlCl3) exposure in the rat kidney. Forty male Wistar rats (5 weeks old), weighing 110-120 g, were randomly divided into four groups: control group (CG, 0 g/L AlCl3), low dose group (LG, 0.4 g/L AlCl3), mid dose group (MG, 0.8 g/L AlCl3), and high dose group (HG, 1.6 g/L AlCl3). Rats were administered AlCl3 in their drinking water for 120 days. A variety of measurements were taken including superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, malondialdehyde (MDA) concentration in the kidney and blood urea nitrogen (BUN), and cystatin C (Cys-C) concentrations in the serum. In addition, Al and β2-microglobulin (β2-MG) concentrations and the activity of N-acetyl-β-D-glucosaminidase (NAG) in the urine were determined. The results showed that in the AlCl3-treated groups SOD and GSH-PX activities were decreased, while NAG activity and Al, MDA, BUN, Cys-C, and β2-MG concentrations were increased, compared with the CG. This study indicates that AlCl3 exposure induces oxidative stress and suppresses kidney function.

  8. Kidney transplantation procedures in rats: assessments, complications, and management.

    PubMed

    Pahlavan, Payam S; Smallegange, Corry; Adams, Michael A; Schumacher, Martin

    2006-01-01

    Kidney transplantation in rats is an experimental model often used for the development of general microsurgical or transplantation techniques, for immunologic studies, and for analyzing transplant-associated long-term arterial blood-pressure changes. The aim of the present study was to analyze different surgical techniques of kidney transplantation in rats, with emphasis on minimizing surgical complications and establishing guidelines for their prevention and management. Complications were categorized into general (e.g., core body temperature drop, ischemic time) and surgically related vascular and urinary tract complications. In conclusion, a significant reduction of the complication rate in renal transplantation in rats can be achieved by placing the animal on a heating pad at an appropriate temperature. To reduce the risk of vascular thrombosis, ice-cold saline with heparin and careful flushing of the donor kidneys are recommended. Vascular complications can be avoided by performing "end-to-end" anastomosis techniques. The use of stents and cannulas in the urinary tract is associated with a high risk of urinary tract obstruction, and therefore is not recommended.

  9. CA V is present in rat kidney mitochondria

    SciTech Connect

    Dodgson, S.J.; Contino, L.C.

    1987-05-01

    Guinea pig liver mitochondria contain the unique carbonic anhydrase isozyme, CA V. Prior to sacrifice, 15 rats and 15 guinea pigs were either fed normal lab chow (group 1), starved 48 hours (group 2) or fed normal lab chow and given to drink only water with added HCl, pH 2.5 (group 3). Mitochondria were prepared from excised livers and kidneys. CA V activity of disrupted mitochondria was measured by /sup 18/O-mass spectrometric technique at pH 7.4, 37/sup 0/C, 25 mM NaHCO/sub 3/. Mass spectrometric CA assays with intact kidney mitochondria localize CA V activity to the matrix, as was found for liver mitochondria. It has been shown in hepatocytes prepared from starved guinea pigs and rats that inhibition of CA V results in decreased rate of gluconeogenesis from pyruvate. These present results are in line with the published observation that rat kidneys are much more gluconeogenic than guinea pig, and that this is increased by starvation and acidosis.

  10. Vitamin D deficiency aggravates ischemic acute kidney injury in rats

    PubMed Central

    de Bragança, Ana Carolina; Volpini, Rildo A; Canale, Daniele; Gonçalves, Janaína G; Shimizu, Maria Heloisa M; Sanches, Talita R; Seguro, Antonio C; Andrade, Lúcia

    2015-01-01

    Vitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which activates cell cycle inhibitors, including p21, a cyclin-dependent kinase inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent immunomodulator with antiproliferative effects. In this study, we assess the impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were euthanized; blood, urine, and kidney tissue samples were collected. Compared with IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration rate, greater urinary protein excretion, a higher kidney/body weight ratio and lower renal aquaporin 2 expression, as well as greater morphological damage, characterized by increased interstitial area and tubular necrosis. Our results suggest that the severity of tubular damage in IRI may be associated with downregulation of vitamin D receptors and p21. VDD increases renal inflammation, cell proliferation and cell injury in ischemic AKI. PMID:25780095

  11. Metabolism of circulating renin by liver and kidney of rats

    SciTech Connect

    Kim, S.; Iwao, H.; Nakamura, N.; Ikemoto, F.; Yamamoto, K.; Mizuhira, V.; Yokofujita, J.

    1987-01-01

    Rat renal renin, highly purified and labeled with /sup 125/I, was intravenously given to conscious rats, to study the fate of the circulating renin. Rat antirenin antiserum was used to identify the labeled renin. The disappearance of (/sup 125/I)-renin from the plasma showed two exponential components and the metabolic clearance rate was 11.4 +/- 1.0 ml/min/kg. Both 70% hepatectomy and bilateral nephrectomy decreased the clearance rate by about 50%. (/sup 125/I)-renin accumulated mainly in the liver and kidney, and high performance liquid chromatography (HPLC) analysis indicated the degradation of (/sup 125/I)-renin by these organs. Biliary excretion of (/sup 125/I)-renin was negligible and urinary excretion accounted for 2% of the injected dose. Light- and electron-microscopic autoradiography indicated that (/sup 125/I)-renin is taken up mainly by Kupffer cells and proximal convoluted tubular cells in the liver and kidney, respectively, and thereafter distributes to the lysosomes. In conclusion, both the liver and kidney are responsible for the clearance of circulating renin.

  12. Accelerated senescence in kidneys of low-birth-weight rats after catch-up growth.

    PubMed

    Luyckx, Valerie A; Compston, Catharine A; Simmen, Thomas; Mueller, Thomas F

    2009-12-01

    Epidemiological studies show a strong association between low birth weight and hypertension, renal, and cardiovascular disease, especially after catch-up growth. Senescence is an important contributor to the progression of chronic disease. Developmentally programmed premature senescence may be a link among low birth weight, catch-up growth, and adult disease. Low birth weight was induced by feeding pregnant rats a low-protein diet from day 12 of gestation to 10 days postdelivery. Low- and normal-birth-weight male offspring were weaned onto regular or high-calorie diets to enhance catch-up growth. Kidneys and hearts of offspring were analyzed for RNA and protein markers of stress-induced senescence (p16, p21, p53, Rb). Markers of mitochondrial stress (p66Shc) and activation of endoplasmic reticulum protein secretion (Ero1alpha) were analyzed as regulators of reactive oxygen species generation. Reactive oxygen species are known to be associated with premature aging. Senescence markers were not different in low- or normal-birth-weight kidneys at birth. During rapid catch-up growth, p16 and p21 increased significantly in low-birth-weight kidneys and hearts (P < 0.01). Renal p16 levels increased progressively and were significantly higher in low-birth-weight kidneys at 3 and 6 mo (P < or = 0.02). Renal p66Shc and Ero1alpha were significantly higher in low- compared with normal- birth-weight kidneys at 6 mo, suggesting reactive oxygen species generation (P < or = 0.03). Low-birth-weight rats exhibit accelerated senescence in kidneys and hearts after rapid catch-up growth, a likely important link between early growth and subsequent hypertension, renal, and cardiovascular disease.

  13. Cell type-specific glycoconjugates of collecting duct cells during maturation of the rat kidney.

    PubMed

    Holthöfer, H

    1988-08-01

    The ontogeny of lectin-positive epithelial cell types and the maturation of polarized expression of the glycocalyx of the collecting ducts (CD) of the rat kidney were studied from samples of 18th-day fetal and neonatal kidneys of various ages. Lectins from Dolichos biflorus (DBA) and Vicia villosa (VVA), with preferential affinity to principal cells, stained virtually all CD cells of the fetal kidneys. However, within two days postnatally, the number of cells positive for DBA and VVA decreased to amounts found in the adult kidneys. Moreover, a characteristic change occurred rapidly after birth in the intracellular polarization of the reactive glycoconjugates, from a uniform plasmalemmal to a preferentially apical staining. In contrast, lectins from Arachis hypogaea (PNA), Maclura pomifera (MPA) and Lotus tetragonolobus (LTA), reacting indiscriminatively with principal and intercalated cells of adult kidneys, stained most CD cells in the fetal kidneys, and failed to show any postnatal change in the amount of positive cells or in the intracellular polarization. The immunocytochemical tests for (Na + K)-ATPase and carbonic anhydrase (CA II) revealed the characteristic postnatal decrease in the amount of principal cells and simultaneous increase in the amount of CA II rich intercalated cells. DBA and VVA reactive cells also decreased postnatally, paralleling the changes observed in the (Na + K)-ATPase positive principal cells. The present results suggest that the expression of the cell type-specific glycocalyx of principal and intercalated cells is developmentally regulated, undergoes profound changes during maturation, and is most likely associated with electrolyte transport phenomena.

  14. Dietary flax oil during pregnancy and lactation retards disease progression in rat offspring with inherited kidney disease.

    PubMed

    Sankaran, Deepa; Bankovic-Calic, Neda; Peng, Claudia Yu-Chen; Ogborn, Malcolm R; Aukema, Harold M

    2006-12-01

    Dietary flax oil (FO) retards disease progression in growing or adult animal models of kidney disease. To determine whether dietary flax oil during the perinatal period would alter renal disease progression in offspring, Han-SPRD-cy rats with inherited cystic kidney disease were given diets with either 7% FO or corn oil (CO), throughout pregnancy and lactation. At 3 wk of age, offspring were then given either the same or the alternate diet for 7 wk. Rats given FO during the maternal period had 15% less renal cyst growth compared with rats given FO only in the postweaning period. Dietary FO, compared with CO, in the maternal period also resulted in 12% lower cell proliferation and 15% less oxidant injury in diseased kidneys of offspring. Including FO in both the maternal and postweaning period resulted in 29-34% less renal interstitial fibrosis and 22-23% lower glomerular hypertrophy. Along with improved histology, these rats exhibited 13% less proteinuria and 30% lower creatinine clearance when dietary FO was given in the maternal period. The potential for dietary FO during pregnancy and lactation to positively modulate adult renal disease has significant implications for the 1 in 1000 individuals with congenital cystic kidney disease.

  15. Effect of Urtica dioica on morphometric indices of kidney in streptozotocin diabetic rats--a stereological study.

    PubMed

    Golalipour, Mohammad Jafar; Gharravi, Anneh Mohammad; Ghafari, Sorya; Afshar, Mohammad

    2007-11-01

    The aim of the present study was to investigate the effect of Urtica dioica on Morphometric indices of kidney in diabetic rats. Thirty male adult albino wistar rats of 125-175 g divided into control, diabetic and Urtica dioica treatment groups. In treatment Group, diabetic rats received 100 mg kg(-1) daily hydroalcoholic extract of U. dioica intraperitoneally for 4 weeks. After the animals had been sacrified, the kidneys were removed and fixed by formaldehyde, cut horizontally into 1 mm slices and processed, Stained with H and E. Stereological study performed using light microscope and the image projected on a table of olysa software. Cavalieri principle was used to estimate the volume of cortex, medulla and whole kidney. All the grouped data statistically evaluated using Student's t-test, expressed as the Mean +/- SE. Ration of kidney weight/body weight in diabetes (0.51) and diabetes-extract group (0.67) were higher then control group (0.42). Ratio of kidney volume/body weight in diabetes (350) and diabetes-extract group (348) were higher then control group (323). Volume Ratio of cortex/medulla in diabetes-extract group (1.65) was higher then control (1.34) and diabetes group (1.33). Glomerular area and diameter and proximal tubule diameter in diabetes-Extract group was higher than control and diabetes groups. This study revealed that Urtica dioica has no effect on renal morphometric indices in induced diabetic rats.

  16. Atlas of Cellular Dynamics during Zebrafish Adult Kidney Regeneration

    PubMed Central

    McCampbell, Kristen K.; Springer, Kristin N.; Wingert, Rebecca A.

    2015-01-01

    The zebrafish is a useful animal model to study the signaling pathways that orchestrate kidney regeneration, as its renal nephrons are simple, yet they maintain the biological complexity inherent to that of higher vertebrate organisms including mammals. Recent studies have suggested that administration of the aminoglycoside antibiotic gentamicin in zebrafish mimics human acute kidney injury (AKI) through the induction of nephron damage, but the timing and details of critical phenotypic events associated with the regeneration process, particularly in existing nephrons, have not been characterized. Here, we mapped the temporal progression of cellular and molecular changes that occur during renal epithelial regeneration of the proximal tubule in the adult zebrafish using a platform of histological and expression analysis techniques. This work establishes the timing of renal cell death after gentamicin injury, identifies proliferative compartments within the kidney, and documents gene expression changes associated with the regenerative response of proliferating cells. These data provide an important descriptive atlas that documents the series of events that ensue after damage in the zebrafish kidney, thus availing a valuable resource for the scientific community that can facilitate the implementation of zebrafish research to delineate the mechanisms that control renal regeneration. PMID:26089919

  17. Definition and Facts for Kidney Stones in Adults

    MedlinePlus

    ... Eating, Diet, & Nutrition Clinical Trials Definition & Facts for Kidney Stones What are kidney stones? Kidney stones are hard, pebble-like pieces ... stone may get stuck along the way. Do kidney stones have another name? The scientific name for ...

  18. Serine synthesis by an isolated perfused rat kidney preparation.

    PubMed Central

    Scaduto, R C; Davis, E J

    1985-01-01

    The isolated perfused rat kidney was shown to synthesize serine from aspartate or glutamate, both of which are also precursors of glucose. The major products of aspartate metabolism were ammonia, serine, glutamate, glucose, glutamine and CO2. Perfusion of kidneys with aspartate in the presence of amino-oxyacetate resulted in a near-complete inhibition of aspartate metabolism, illustrating the essential role of aspartate aminotransferase in the metabolism of this substrate. Radioactivity from 14C-labelled aspartate and from 14C-labelled glycerol was incorporated into serine and glucose. Production of both glucose and serine from aspartate was suppressed in the presence of 3-mercaptopicolinic acid. These data provide evidence for the operation of the phosphorylated and/or non-phosphorylated pathway for serine production to the presence of 3-mercaptopicolinic acid. This is explained by simultaneous glycolysis. The rate of glucose production, but not that of serine, was greater in kidneys perfused with glutamate or with aspartate plus glycerol than the rates obtained by perfusion with aspartate alone. These data are taken to suggest that serine synthesis occurred at a near-maximal rate, and that the capacity of the kidney for serine synthesis from glucose precursors is lower than that for glucose synthesis. PMID:2864920

  19. Moderate aerobic exercise on the recovery phase of gentamicin-induced acute kidney injury in rats.

    PubMed

    Oliveira, C S; Rodrigues, A M; Nogueira, G B; Nascimento, M A; Punaro, G R; Higa, E M S

    2017-01-15

    Acute kidney injury is a serious public health problem, especially in intensive care units, where patients may require dialysis support, resulting in 50% mortality. To evaluate the effects of moderate aerobic exercise on the recovery phase of acute kidney injury induced by gentamicin in rats. Male adult Wistar rats were allocated into 4 groups: W10+R30, G10+R30, W10+EX30 and G10+EX30; W10 received water (gentamicin vehicle) and G10 received gentamicin for 10days; R30 remained resting and EX30 made exercise for 30days after gentamicin suspension. Training was performed on treadmill. Blood, 24h urine and kidneys were collected for renal function and oxidative stress, antioxidant, TGF-β and histological analysis. Gentamicin treatment caused decreased renal function significant oxidative stress, reduced urinary nitric oxide and increased TGF-β. G10+R30 presented partial recovery of metabolic data, renal function and lipoperoxidation levels, although they were still altered compared to W10+R30. Besides, we observed the presence of lymphomononuclear infiltrate in the kidneys of G10+R30. G10+EX30 vs G10+R30 showed additional improvement of all the mentioned parameters, showing at histology, regeneration of the tubule epithelium. Our data suggest that moderate exercises could help in the recovery of metabolic parameters, renal function and structure on gentamicin-induced AKI, perhaps due to restoration of redox balance. This could protect the kidneys from further insults like challenges with nephrotoxic drugs or the aging per se. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Dietary fructose causes tubulointerstitial injury in the normal rat kidney

    PubMed Central

    Nakayama, Takahiro; Kosugi, Tomoki; Gersch, Michael; Connor, Thomas; Sanchez-Lozada, Laura Gabriela; Lanaspa, Miguel A.; Roncal, Carlos; Perez-Pozo, Santos E.; Johnson, Richard J.

    2010-01-01

    Recent studies suggest that the metabolic syndrome is associated with renal disease. We previously reported that a high-fructose diet, but not a high-glucose diet, can induce metabolic syndrome and accelerate chronic renal disease in rats. We now examined the effects of a high-fructose diet on normal rat kidneys. Three groups of Sprague-Dawley rats were pair fed a special diet containing 60% fructose, 60% glucose, or control standard rat chow for 6 wk, and then histological studies were performed. The effect of fructose to induce cell proliferation in cultured proximal tubular cells was also performed. Fructose diet, but not glucose diet, significantly increased kidney weight by 6 wk. The primary finding was tubular hyperplasia and proliferation involving all segments of the proximal tubules while glomerular changes were not observed. This is the same site where the fructose transporters (GLUT2 and -5) as well as the key enzyme in fructose metabolism (ketohexokinase) were expressed. Consistently, fructose also induced proliferation of rat proximal tubular cells in culture. In vivo, tubular proliferation was also associated with focal tubular injury, with type III collagen deposition in the interstitium, an increase in α-smooth muscle actin positive myofibroblasts, and an increase in macrophage infiltration. In conclusion, a high-fructose diet induces cell proliferation and hyperplasia in proximal tubules, perhaps via a direct metabolic effect. The effect is independent of total energy intake and is associated with focal tubulointerstitial injury. These studies may provide a mechanism by which metabolic syndrome causes renal disease. PMID:20071464

  1. Dietary fructose causes tubulointerstitial injury in the normal rat kidney.

    PubMed

    Nakayama, Takahiro; Kosugi, Tomoki; Gersch, Michael; Connor, Thomas; Sanchez-Lozada, Laura Gabriela; Lanaspa, Miguel A; Roncal, Carlos; Perez-Pozo, Santos E; Johnson, Richard J; Nakagawa, Takahiko

    2010-03-01

    Recent studies suggest that the metabolic syndrome is associated with renal disease. We previously reported that a high-fructose diet, but not a high-glucose diet, can induce metabolic syndrome and accelerate chronic renal disease in rats. We now examined the effects of a high-fructose diet on normal rat kidneys. Three groups of Sprague-Dawley rats were pair fed a special diet containing 60% fructose, 60% glucose, or control standard rat chow for 6 wk, and then histological studies were performed. The effect of fructose to induce cell proliferation in cultured proximal tubular cells was also performed. Fructose diet, but not glucose diet, significantly increased kidney weight by 6 wk. The primary finding was tubular hyperplasia and proliferation involving all segments of the proximal tubules while glomerular changes were not observed. This is the same site where the fructose transporters (GLUT2 and -5) as well as the key enzyme in fructose metabolism (ketohexokinase) were expressed. Consistently, fructose also induced proliferation of rat proximal tubular cells in culture. In vivo, tubular proliferation was also associated with focal tubular injury, with type III collagen deposition in the interstitium, an increase in alpha-smooth muscle actin positive myofibroblasts, and an increase in macrophage infiltration. In conclusion, a high-fructose diet induces cell proliferation and hyperplasia in proximal tubules, perhaps via a direct metabolic effect. The effect is independent of total energy intake and is associated with focal tubulointerstitial injury. These studies may provide a mechanism by which metabolic syndrome causes renal disease.

  2. Primary primitive neuroectodermal tumour of the kidney in adults.

    PubMed

    Verma, Ritu; Singhal, Mitali; Pandey, Rakesh

    2013-03-04

    Primitive neuroectodermal tumour (PNET) is a neural crest tumour derived from neuroectoderm. Renal PNET is a very rare tumour occurring during childhood or adolescence. We report two cases of PNET involving kidney in adults. Presenting signs and symptoms include abdominal/flank pain and/or haematuria. Microscopy reveals the tumour consisted of small round cells with round nuclei and scant cytoplasm. Diagnosis was confirmed by immunohistochemistry with diffuse membranous positivity of tumour cells with CD99. As these tumours have an aggressive clinical course with rapid death in many reported cases, it is important to differentiate them from other small round-cell tumours.

  3. The Expression Changes of Inflammasomes in the Aging Rat Kidneys.

    PubMed

    Song, Fei; Ma, Yuxiang; Bai, Xue-Yuan; Chen, Xiangmei

    2016-06-01

    The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Inflammasomes are important components of innate immune system in the body. However, the function of inflammasomes and their underlying mechanisms in renal aging remain unclear. In this study, for the first time, we systematically investigated the role of the inflammasomes and the inflammatory responses activated by inflammasomes during kidney aging. We found that during kidney aging, the expression levels of the molecules associated with the activation of inflammasomes, including toll-like receptor-4 and interleukin-1 receptor (IL-1R), were significantly increased; their downstream signaling pathway molecule interleukin-1 receptor-associated kinase-4 (IRAK4) was markedly activated (Phospho-IRAK4 was obviously increased); the nuclear factor-κB (NF-κB) signaling pathway was activated (the activated NF-κB pathway molecules Phospho-IKKβ, Phospho-IκBα, and Phospho-NF-κBp65 were significantly elevated); the levels of the inflammasome components NOD-like receptor P3 (NLRP3), NLRC4, and pro-caspase-1 were prominently upregulated; and the proinflammatory cytokines IL-1β and IL-18 were notably increased in the kidneys of 24-month-old (elderly group) rats. These results showed that inflammasomes are markedly activated during the renal aging process and might induce inflamm-aging by promoting the maturation and secretion of the proinflammatory cytokines IL-1β and IL-18. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Protective Effect of Dihydromyricetin Against Lipopolysaccharide-Induced Acute Kidney Injury in a Rat Model.

    PubMed

    Wang, Jun-Tao; Jiao, Peng; Zhou, Yun; Liu, Qian

    2016-02-11

    BACKGROUND The present study investigated the effect of dihydromyricetin (DHM) on lipopolysaccharide (LPS)-induced acute kidney injury in a rat model. MATERIAL AND METHODS Kidney injury was induced in male Sprague-Dawley rats by injection of LPS through the tail vein. The rats were treated with 5 µg/kg body weight DHM within 12 h of the LPS administration. The urine of the rats was collected over a period of 48 h for determination of calcium and creatinine concentrations. Blood urea nitrogen in the serum was analyzed using a BC-2800 Vet Animal Auto Biochemistry Analyzer. On day 3 after treatment, the rats were sacrificed to extract the kidneys. RESULTS Treatment of the endotoxemia rats with DHM caused a significant (P<0.05) decrease in the level of kidney injury molecule‑1 and blood urea nitrogen. DHM treatment significantly (P<0.05) decreased the level of calcium in the kidney tissues compared to those of the untreated endotoxemia rats. The level of malonaldehyde (MDA) in the kidney tissues was significantly reduced in the endotoxemia rats by DHM treatment. The results from immunohistochemistry reveled a significant decrease in the expression of osteopontin (OPN) and CD44 levels. The endotoxemia rats showed significantly higher levels of TUNEL-positive stained nuclei compared to the normal controls. However, treatment of the endotoxemia rats with DHM resulted in a significant decrease in the population of TUNEL-positive cells. CONCLUSIONS DHM may be a promising candidate for the treatment of acute kidney injury.

  5. Impact of growth hormone hypersecretion on the adult human kidney.

    PubMed

    Grunenwald, Solange; Tack, Ivan; Chauveau, Dominique; Bennet, Antoine; Caron, Philippe

    2011-12-01

    Acromegaly is most often secondary to a GH-secreting pituitary adenoma with increased Insulin-like Growth Factor type 1 (IGF-1) level. The consequences of GH/IGF-1 hypersecretion reflect the diversity of action of these hormones. The genes of the GH receptor (GHR), IGF-1, IGF-1 receptor (IGF-1R) and IGF-binding proteins (IGF-BP) are physiologically expressed in the adult kidney, suggesting a potential role of the somatotropic axis on renal structure and functions. The expression of these proteins is highly organized and differs according to the anatomical and functional segments of the nephron suggesting different roles of GH and IGF-1 in these segments. In animals, chronic exposure to high doses of GH induces glomerulosclerosis and increases albuminuria. Studies in patients with GH hypersecretion have identified numerous targets of GH/IGF-1 axis on the kidney: 1) an impact on renal filtration with increased glomerular filtration rate (GFR), 2) a structural impact with an increase in kidney weight and glomerular hypertrophy, and 3) a tubular impact leading to hyperphosphatemia, hypercalciuria and antinatriuretic effects. Despite the increased glomerular filtration rate observed in patients with GH hypersecretion, GH is an inefficient treatment for chronic renal failure. GH and IGF-1 seem to be involved in the physiopathology of diabetic nephropathy; this finding offers the possibility of targeting the GH/IGF-1 axis for the prevention and the treatment of diabetic nephropathy. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  6. Increased kidney metabolism as a pathway to kidney tissue hypoxia and damage: effects of triiodothyronine and dinitrophenol in normoglycemic rats.

    PubMed

    Friederich-Persson, Malou; Persson, Patrik; Fasching, Angelica; Hansell, Peter; Nordquist, Lina; Palm, Fredrik

    2013-01-01

    Intrarenal tissue hypoxia is an acknowledged common pathway to end-stage renal disease in clinically common conditions associated with development of chronic kidney disease, such as diabetes and hypertension. In diabetic kidneys, increased oxygen metabolism mediated by mitochondrial uncoupling results in decreased kidney oxygen tension (PO2) and contributes to the development of diabetic nephropathy. The present study investigated whether increased intrarenal oxygen metabolism per se can cause intrarenal tissue hypoxia and kidney damage, independently of confounding factors such as hyperglycemia and oxidative stress. Male Sprague-Dawley rats were untreated or treated with either triiodothyronine (T3, 10 g/kg bw/day, subcutaneously for 10 days) or the mitochondria uncoupler dinitrophenol (DNP, 30 mg/kg bw/day, oral gavage for 14 days), after which in vivo kidney function was evaluated in terms of glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Transonic, PAH clearance), cortical PO2 (Clark-type electrodes), kidney oxygen consumption (QO2), and proteinuria. Administration of both T3 and DNP increased kidney QO2 and decreased PO2 which resulted in proteinuria. However, GFR and RBF were unaltered by either treatment. The present study demonstrates that increased kidney metabolism per se can cause intrarenal tissue hypoxia which results in proteinuria. Increased kidney QO2 and concomitantly reduced PO2 may therefore be a mechanism for the development of chronic kidney disease and progression to end-stage renal disease.

  7. P2-receptor modulation of noradrenergic neurotransmission in rat kidney

    PubMed Central

    Bohmann, Christine; von Kügelgen, Ivar; Christian Rump, L

    1997-01-01

    ATP has previously been shown to act as a sympathetic cotransmitter in the rat kidney. The present study analyses the question of whether postganglionic sympathetic nerve endings in the kidney possess P2-receptors which modulate noradrenaline release. Rat kidneys were perfused with Krebs-Henseleit solution containing the noradrenaline uptake blockers cocaine and corticosterone and the α2-adrenoceptor antagonist rauwolscine. The renal nerves were electrically stimulated, in most experiments by 30 pulses applied at 1 Hz. The outflow of endogenous noradrenaline (or, in some experiments, of ATP and lactate dehydrogenase) as well as the perfusion pressure were measured simultaneously. The P2-receptor agonist adenosine-5′-O-(3-thiotriphosphate) (ATPγS, 3–30 μM) reduced the renal nerve stimulation (RNS)-induced outflow of noradrenaline (estimated EC50=8 μM). The P2-receptor antagonist cibacron blue 3GA (30 μM) shifted the concentration-inhibition curve for ATPγS to the right (apparent pKB value 4.7). Cibacron blue 3GA (3–30 μM) and its isomer reactive blue 2 (3–30 μM) significantly increased RNS-induced outflow of noradrenaline in the presence of the P1-receptor antagonist 8-(p-sulphophenyl)theophylline (8-SPT, 100 μM) by about 70% and 90%, respectively. The P2-receptor antagonist suramin (30–300 μM) only tended to enhance RNS-induced outflow of noradrenaline. When the nerves were stimulated by short pulse trains consisting of 6 pulses applied at 100 Hz (conditions under which autoinhibition is inoperative), reactive blue 2 did not affect the RNS-induced outflow of noradrenaline. RNS (120 pulses applied at 4 Hz) induced the outflow of ATP but not of the cytoplasmatic enzyme lactate dehydrogenase. ATPγS (3–30 μM) concentration-dependently reduced pressor responses to RNS at 1 Hz. Cibacron blue 3GA, reactive blue 2 as well as suramin also reduced pressor responses to RNS (maximally by 50 to 70%). This study in rat isolated

  8. Effects of gonadectomy and testosterone treatment on aquaporin expression in the kidney of normotensive and hypertensive rats.

    PubMed

    Loh, Su Yi; Giribabu, Nelli; Salleh, Naguib

    2017-07-01

    We tested the hypothesis that testosterone-induced increase in blood pressure was due to changes in aquaporin (AQP) expression in kidneys. In this study, expression level of kidney AQPs was investigated under testosterone influence. Adult normotensive Wistar Kyoto (WKY) and hypertensive SHR male and female rats underwent gonadectomy. For female rats, testosterone was given for six weeks duration, two weeks following ovariectomy via subcutaneous silastic implant. Mean arterial pressure (MAP) was measured in all the rats after eight weeks via carotid artery cannulation and the rats were then sacrificed and kidneys were harvested for analyses of AQP-1, 2, 3, 4, 6, and 7 mRNA and protein expressions by quantitative real-time PCR and Western blotting, respectively. Distribution of AQP subunits' protein in kidneys was observed by immunofluorescence. In male WKY rats, MAP, AQP-1, 2, 4, and 7 protein; and mRNA expression decreased however AQP-3 protein and mRNA expression increased following orchidectomy. The vice versa effects were observed in testosterone-treated ovariectomized female WKY rats. However, no changes in AQP-6 expression were observed. Meanwhile, in adult male SHR rats, MAP and expression level of all AQP subunits decreased following orchidectomy. The opposite effects were seen in ovariectomized female SHR rats following testosterone treatment. Immunofluorescence study showed AQP-1 and AQP-7 were distributed in the proximal convoluted tubules (PCT) while AQP-2, AQP-4, and AQP-6 were distributed in the collecting ducts (CDs). AQP-3 was distributed in the PCT and CD. In conclusion, changes in AQP subunit expression in kidneys could explain changes in blood pressure under testosterone influence. Impact statement This study provides fundamental understanding on the mechanisms underlying testosterone-induced increase in blood pressure which involve regulation of aquaporin channel subunits in the kidneys. A better understanding of this issue can help to explain

  9. Electronegative LDL-mediated cardiac electrical remodeling in a rat model of chronic kidney disease

    PubMed Central

    Lee, An-Sheng; Chen, Wei-Yu; Chan, Hua-Chen; Chung, Ching-Hu; Peng, Hsien-Yu; Chang, Chia-Ming; Su, Ming-Jai; Chen, Chu-Huang; Chang, Kuan-Cheng

    2017-01-01

    The mechanisms underlying chronic kidney disease (CKD)–associated higher risks for life-threatening ventricular tachyarrhythmias remain poorly understood. In rats subjected to unilateral nephrectomy (UNx), we examined cardiac electrophysiological remodeling and relevant mechanisms predisposing to ventricular arrhythmias. Adult male Sprague-Dawley rats underwent UNx (n = 6) or sham (n = 6) operations. Eight weeks later, the UNx group had higher serum blood urea nitrogen and creatinine levels and a longer electrocardiographic QTc interval than did the sham group. Patch-clamp studies revealed epicardial (EPI)-predominant prolongation of the action potential duration (APD) at 50% and 90% repolarization in UNx EPI cardiomyocytes compared to sham EPI cardiomyocytes. A significant reduction of the transient outward potassium current (Ito) in EPI but not in endocardial (ENDO) cardiomyocytes of UNx rats led to a decreased transmural gradient of Ito. The reduction of Ito currents in UNx EPI cardiomyocytes was secondary to downregulation of KChIP2 but not Kv4.2, Kv4.3, and Kv1.4 protein expression. Incubation of plasma electronegative low-density lipoprotein (LDL) from UNx rats with normal EPI and ENDO cardiomyocytes recapitulated the electrophysiological phenotype of UNx rats. In conclusion, CKD disrupts the physiological transmural gradient of Ito via downregulation of KChIP2 proteins in the EPI region, which may promote susceptibility to ventricular tachyarrhythmias. Electronegative LDL may underlie downregulation of KChIP2 in CKD. PMID:28094801

  10. Rapid Kidney Function Decline and Mortality Risk in Older Adults

    PubMed Central

    Rifkin, Dena E.; Shlipak, Michael G.; Katz, Ronit; Fried, Linda F.; Siscovick, David; Chonchol, Michel; Newman, Anne B.; Sarnak, Mark J.

    2010-01-01

    Background Impaired kidney function is associated with increased mortality risk in older adults. It remains unknown, however, whether longitudinal declines in kidney function are independently associated with increased cardiovascular and all-cause mortality in older adults. Methods The Cardiovascular Health Study evaluated a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration rate (eGFR) was estimated using both serum creatinine (eGFRcreat) and cystatin C (eGFRcys) rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in eGFR was defined as a loss greater than 3 mL/min/1.73 m2 per year, and cardiovascular and all-cause mortality were assessed over a mean of 9.9 years of follow-up. Results Mean (SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean (SD) eGFRcreat and eGFRcys were 79 (23) mL/min/1.73 m2 and 79 (19) mL/min/1.73 m2, respectively. Individuals with rapid decline measured by eGFRcreat (n=714; 16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence interval [CI], 1.40–2.06) and all-cause (AHR, 1.73; 95% CI, 1.54–1.94) mortality. Individuals with rapid decline measured by eGFRcys (n=1083; 25%) also had increased risk of cardiovascular (AHR, 1.53; 95% CI, 1.29–1.80) and all-cause (AHR, 1.53; 95% CI, 1.38–1.69) mortality. The association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, race, or prevalent coronary heart disease. Conclusion Rapid decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older adults, independent of baseline eGFR and other demographic variables. PMID:19001197

  11. Renal disposition of colistin in the isolated perfused rat kidney.

    PubMed

    Ma, Zheng; Wang, Jiping; Nation, Roger L; Li, Jian; Turnidge, John D; Coulthard, Kingsley; Milne, Robert W

    2009-07-01

    Nephrotoxicity is an important limitation to the clinical use of colistin against Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported net tubular reabsorption of colistin by the kidney in vivo, but there is no knowledge of its disposition within the kidney. This study investigated the renal disposition and potential transport mechanisms of colistin in the isolated perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2 microg/ml) or in the presence of potential inhibitors (tetraethylammonium [TEA], glycine-glycine [Gly-Gly], or hydrochloric acid [HCl]) at three different concentrations. When perfused alone, the renal clearances (CL(R)) for colistin A and B (the major components of colistin) in control kidneys were constant and low (mean values < 0.05 ml/min throughout the perfusion). The mean clearance ratios [CR, defined as CL(R)/(f(u) x GFR), where f(u) is the fraction of drug unbound in perfusate and GFR is the glomerular filtration rate] were significantly less than 1. It was concluded that there is net tubular reabsorption of colistin, and this exceeded the reabsorption of water. Less than 10% eliminated from perfusate was recovered in urine, suggesting considerable renal accumulation of colistin. The CR values for colistin were significantly increased when perfused with TEA (500 microM), Gly-Gly (833 microM), and HCl (2,500, 5,000, and 10,000 microM). It is proposed that renal reabsorption of colistin may involve organic cation transporters (inhibited by TEA) and peptide transporters (inhibited by Gly-Gly) and that the process is sensitive to the pH of urine.

  12. Metabolism of cysteine and cysteinesulfinate in rat kidney tubules

    SciTech Connect

    De La Rosa, J.; Stipanuk, M.H.

    1986-05-01

    In studies with rat hepatocytes, hypotaurine plus taurine production accounted for less than 5% of the total amount of cysteine (CYS) catabolized, whereas more than 90% of the metabolized cysteinesulfinate (CSA) was converted to taurine plus hypotaurine. Similar studies have been carried out with kidney tubules isolated from fed rats and incubated with 2 mM (1-/sup 14/C)CYS or 25 mM (1-/sup 14/C)CSA at 37/sup 0/C for up to 40 min. The production of /sup 14/CO/sub 2/ from CSA (3.1 +/- 1.3 nmol/sup ./ min/sup -1//sup ./ mg dry wt/sup -1/) was equivalent to the accumulation of N in NH/sub 4//sup +/ plus glutamate. Substantial oxidation of CYS was observed (16 +/- 11 nmol CO/sub 2/ x min/sup -1/ x mg dry wt/sup -1/), but only 12% of the expected amount of N was recovered as NH/sub 4//sup +/ plus glutamate. Accumulation of hypotaurine plus taurine was equivalent to 20% of the observed rate of /sup 14/CO/sub 2/ production from CSA but accounted for only 2% of the observed rate of /sup 14/CO/sub 2/ production from CYS. Addition of unlabeled CSA to incubations with varying levels of CYS had no effect on production of /sup 14/CO/sub 2/. Addition of 2 mM ..cap alpha..-ketoglutarate to the incubation mixtures resulted in an increased in /sup 14/CO/sub 2/ production from CSA to 290% of the control level but had no effect on CYS oxidation. In agreement with the authors findings for rat hepatocytes, these data suggest that most metabolism of CYS by the rat kidney tubule occurs by a CSA-independent pathway. However, in contrast to the metabolism of CSA almost entirely to taurine in the hepatocyte, kidney tubules appeared to metabolize CSA primarily by the transamination pathway.

  13. Effects of ubiquinol with fluid resuscitation following haemorrhagic shock on rat lungs, diaphragm, heart and kidneys.

    PubMed

    Bennetts, Paul; Shen, Qiuhua; Thimmesch, Amanda R; Diaz, Francisco J; Clancy, Richard L; Pierce, Janet D

    2014-07-01

    Haemorrhagic shock (HS) and fluid resuscitation can lead to increased reactive oxygen species (ROS), contributing to ischaemia-reperfusion injury and organ damage. Ubiquinol is a potent antioxidant that decreases ROS. This study examined the effects of ubiquinol administered with fluid resuscitation following controlled HS. Adult male Sprague-Dawley rats were randomly assigned to treatment [ubiquinol, 1 mg (100 g body weight)(-1)] or control groups. Rats were subjected to 60 min of HS by removing 40% of the total blood volume to a mean arterial pressure ∼45-55 mmHg. The animals were resuscitated with blood and lactated Ringer solution, with or without ubiquinol, and monitored for 120 min. At the end of the experiments, the rats were killed and the lungs, diaphragm, heart and kidneys harvested. Leucocytes were analysed for mitochondrial superoxide at baseline, end of shock and 120 min following fluid resuscitation using MitoSOX Red. Diaphragms were examined for hydrogen peroxide using dihydrofluorescein diacetate and confocal microscopy. The apoptosis in lungs, diaphragm, heart and kidneys was measured using fluorescence microscopy with acridine orange and ethidium bromide. Leucocyte mitochondrial superoxide levels were significantly lower in rats that received ubiquinol than in the control animals. Production of hydrogen peroxide and apoptosis were significantly reduced in the organs of rats treated with ubiquinol. These findings suggest that ubiquinol, administered with fluid resuscitation after HS, attenuates ROS production and apoptosis. Thus, ubiquinol is a potent antioxidant that may be used as a potential treatment to reduce organ injury following haemorrhagic events. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  14. Prevalence of chronic kidney disease in an adult population.

    PubMed

    Cueto-Manzano, Alfonso M; Cortés-Sanabria, Laura; Martínez-Ramírez, Héctor R; Rojas-Campos, Enrique; Gómez-Navarro, Benjamin; Castillero-Manzano, Marcelo

    2014-08-01

    One strategy to prevent and manage chronic kidney disease (CKD) is to offer screening programs. The aim of this study was to determine the percentage prevalence and risk factors of CKD in a screening program performed in an adult general population. This is a cross-sectional study. Six-hundred ten adults (73% women, age 51 ± 14 years) without previously known CKD were evaluated. Participants were subjected to a questionnaire, blood pressure measurement and anthropometry. Glomerular filtration rate estimated by CKD-EPI formula and urine tested with albuminuria dipstick. More than 50% of subjects reported family antecedents of diabetes mellitus (DM), hypertension and obesity, and 30% of CKD. DM was self-reported in 19% and hypertension in 29%. During screening, overweight/obesity was found in 75%; women had a higher frequency of obesity (41 vs. 34%) and high-risk abdominal waist circumference (87 vs. 75%) than men. Hypertension (both self-reported and diagnosed in screening) was more frequent in men (49%) than in women (38%). CKD was found in 14.7%: G1, 5.9%; G2, 4.5%; G3a, 2.6%; G3b, 1.1%, G4, 0.3%; and G5, 0.3%. Glomerular filtration rate was mildly/moderately reduced in 2.6%, moderately/severely reduced in 1.1%, and severely reduced in <1%. Abnormal albuminuria was found in 13%. CKD was predicted by DM, hypertension and male gender. A percentage CKD prevalence of 14.7% was found in this sample of an adult population, with most patients at early stages. Screening programs constitute excellent opportunities in the fight against kidney disease, particularly in populations at high risk. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  15. Zinc prevention of electromagnetically induced damage to rat testicle and kidney tissues.

    PubMed

    Ozturk, Ahmet; Baltaci, Abdülkerim Kasim; Mogulkoc, Rasim; Oztekin, Esma

    2003-01-01

    The aim of this study was to investigate the extent of lipid peroxidation when zinc is administered to rats periodically exposed to a 50-Hz electromagnetic field for 5 min at a time over a period of 6 mo. Twenty-four Sprague-Dawley adult male rats were subdivided in groups of eight animals each. Group 1 served as untreated controls, group 2 was exposed to an electromagnetic field but received no additional treatment, and group 3 was exposed to electromagnetic radiation and treated with 3-mg/kg daily intraperitoneal injections of zinc sulfate. The erythrocyte glutathione activity (GSH) and the plasma, testicle, and kidney tissue levels of zinc (Zn) and of malondialdehyde (MDA) were measured in all of the animals. The plasma and testicle MDA levels in group 2 were higher than those in groups 1 and 3, with group 3 values significantly higher than those in group 1 (p<0.001). The kidney MDA levels in group 2 were higher than in groups 1 and 3 (p<0.001). The erythrocyte GSH level was lower in group 2 than in groups 1 and 3, with group 1 significantly lower than group 3 (p<0.001). In testicle and kidney tissues, the GSH levels in group 1 were lower than for groups 2 and 3, with group 2 significantly lower than group 3 (p<0.001) The plasma zinc levels were highest in group 3, followed by group 1 and group 2, which showed the lowest value (p<0.001). These results indicate that testicle and kidney tissue damage caused by periodic exposure to an electromagnetic field are ameliorated or prevented by zinc supplementation.

  16. Protection of resveratrol on acute kidney injury in septic rats.

    PubMed

    Gan, Y; Tao, S; Cao, D; Xie, H; Zeng, Q

    2017-10-01

    The aim of the study is to investigate protective effect of resveratrol (Res) on acute kidney injury (AKI) in sepsis. Rats in sham group received sham operation; in sham + Res received sham operation and Res (3 mg/kg); in cecal ligation and puncture (CLP) established as sepsis; in CLP + Res (3 mg/kg) with sepsis and Res (3 mg/kg); and in CLP + Res (10 mg/kg) with sepsis and Res (10 mg/kg). Survival rate, serum indexes, inflammatory factors, NF-κB-P65, and SIRT1 were detected. Lipopolysaccharide (LPS) mesangial cell was with Res and SIRT1 silencing. (1) Res intervention improved survival rate of CLP rat. (2) Compared to sham, serum creatinine, blood urine nitrogen, serum cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, tumor necrosis factor-α, interleukin-1β, IL-6, and renal injury index increased in CLP group, while decreased in CLP + Res (3 mg/kg) and CLP + Res (10 mg/kg), significantly, as dose-dependent ( p < 0.05). (3) With Res, NF-κB-P65 and de-acetylated SIRT1 decreased, while SIRT1 and de-acetylated Nuclear factor kB-p65 9 NF-κB-P65) increased, significantly ( p < 0.05). (4) SIRT1 and de-acetylated NF-κB-P65 decreased in LPS cells, while SIRT1 increased after Res intervention, significantly ( p < 0.05). After silencing SIRT1, de-acetylated NF-κB-P65 increased, significantly ( p < 0.05). Res increases the survival rate of septic rats by inhibiting inflammatory factors to ease AKI and promotes NF-κB-P65 de-acetylation by upregulating SIRT1.

  17. [Activity of antioxidant enzymes of the rat kidneys under mercury dichloride effect].

    PubMed

    Velyka, A Ia; Pshak, V P; Lopushins'ka, I V

    2014-01-01

    Salts of heavy metals are excreted by the kidneys and, as pro-oxidants, stimulate the processes of free radical oxidation. Mercury ions are accumulated in the kidneys. So the study of the features of antioxidant enzymes adaptive response of different kidney layers in response to mercury dichloride is important. Catalase and glytathionperoxidase activity within rat kidneys 72 hours after mercury dichloride intoxication in the ratio of 5 ml per 1 kg of the animal weight was studied. It was important to reveal the influence of the mercury salts on rat kidney antioxidative system. Decreasing glytathionperoxidase activity in cortical and cerebral substances and renal papillae were accompanied by increased contents of oxidative modified proteins and lipids and morphological changes in renal tissue under salt and water loading after mercury dichloride poisoning. The results obtained evidence for the inhibition of antioxidative protection of enzymes in rat kidneys under the mercury dichloride effect.

  18. Community-acquired acute kidney injury in adults in Africa.

    PubMed

    Adu, Dwomoa; Okyere, Perditer; Boima, Vincent; Matekole, Michael; Osafo, Charlotte

    We review recent published data on demographics, causes, diagnoses, treatment, and outcome of acute kidney injury (AKI) in Africa. A review of the incidence, etiology, diagnoses, and treatment of AKI in adults in Africa from studies published between the years 2000 and 2015. The incidence of AKI in hospitalized patients in Africa ranges from 0.3 to 1.9% in adults. Between 70 and 90% of cases of AKI are community acquired. Most patients with AKI are young with a weighted mean age of 41.3 standard deviation (SD) 9.3 years, and a male to female ratio of 1.2 : 1.0. Medical causes account for between 65 and 80% of causes of AKI. This is followed by obstetric causes in 5 - 27% of cases and surgical causes in 2 - 24% of cases. In the reported studies, between 17 and 94% of patients who needed dialysis received this. The mortality of AKI in adults in Africa ranged from 11.5 to 43.5%. Most reported cases of AKI in Africa originate in the community. The low incidence of hospital-acquired AKI is likely to be due to under ascertainment. Most patients with AKI in Africa are young and have a single precipitating cause. Prominent among these are infection, pregnancy complications and nephrotoxins. Early treatment can improve clinical outcomes.

  19. Risk factors for fracture in adult kidney transplant recipients

    PubMed Central

    Naylor, Kyla L; Zou, Guangyong; Leslie, William D; Hodsman, Anthony B; Lam, Ngan N; McArthur, Eric; Fraser, Lisa-Ann; Knoll, Gregory A; Adachi, Jonathan D; Kim, S Joseph; Garg, Amit X

    2016-01-01

    AIM: To determine the general and transplant-specific risk factors for fractures in kidney transplant recipients. METHODS: We conducted a cohort study of all adults who received a kidney-only transplant (n = 2723) in Ontario, Canada between 2002 and 2009. We used multivariable Cox proportional hazards regression to determine general and transplant-specific risk factors for major fractures (proximal humerus, forearm, hip, and clinical vertebral). The final model was established using the backward elimination strategy, selecting risk factors with a P-value ≤ 0.2 and forcing recipient age and sex into the model. We also assessed risk factors for other fracture locations (excluding major fractures, and fractures involving the skull, hands or feet). RESULTS: There were 132 major fractures in the follow-up (8.1 fractures per 1000 person-years). General risk factors associated with a greater risk of major fracture were older recipient age [adjusted hazard ratio (aHR) per 5-year increase 1.11, 95%CI: 1.03-1.19] and female sex (aHR = 1.81, 95%CI: 1.28-2.57). Transplant-specific risk factors associated with a greater risk of fracture included older donor age (5-year increase) (aHR = 1.09, 95%CI: 1.02-1.17) and end-stage renal disease (ESRD) caused by diabetes (aHR = 1.72, 95%CI: 1.09-2.72) or cystic kidney disease (aHR = 1.73, 95%CI: 1.08-2.78) (compared to glomerulonephritis as the reference cause). Risk factors across the two fracture locations were not consistent (major fracture locations vs other). Specifically, general risk factors associated with an increased risk of other fractures were diabetes and a fall with hospitalization prior to transplantation, while length of time on dialysis, and renal vascular disease and other causes of ESRD were the transplant-specific risk factors associated with a greater risk of other fractures. CONCLUSION: Both general and transplant-specific risk factors were associated with a higher risk of fractures in kidney transplant

  20. Kidney Toxicity Induced by 13 Weeks Exposure to the Fruiting Body of Paecilomyces sinclairii in Rats

    PubMed Central

    Jeong, Mihye; Kim, Young-Won; Min, Jeong-Ran; Kwon, Min; Han, Beom-Suk; Kim, Jeong-Gyu

    2012-01-01

    Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (β2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced. PMID:24278608

  1. Kidney Toxicity Induced by 13 Weeks Exposure to the Fruiting Body of Paecilomyces sinclairii in Rats.

    PubMed

    Jeong, Mihye; Kim, Young-Won; Min, Jeong-Ran; Kwon, Min; Han, Beom-Suk; Kim, Jeong-Gyu; Jeong, Sang-Hee

    2012-09-01

    Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (β2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

  2. Postnatal development of the kidney juxtaglomerular apparatus in rats.

    PubMed

    Vesna, L; Spomenka, M

    1980-01-01

    The development of the juxtaglomerular (JG) apparatus in the rat kidney was investigated at different times of postnatal life (1, 2, 3, 5, 7, 10, 15, 30 and 60 days). On the 1st day after birth, secretory granules were found in JG cells in preglomerular arterioles of juxtamedular nephrons and in interglobular arteries. JG indices are high at this stage and decrease until the 5th day, then gradually rise until the 60th day. The possible reasons for such findings are discussed. Macula densa cells start to differ as early as the 1st day after birth. They are very distinct already at 2 days and they reach typical organization by the 15th day. Extraglomerular mesangial cells are few in early postnatal life. Their number increases later on. The parallelism between nephrogenesis and development is discussed.

  3. Early metabolic effects of hypotension on rat kidney.

    PubMed

    Freeman, D M; Chan, L; Yahaya, H; Holloway, P; Ross, B D

    1989-01-01

    Saturation-transfer phosphorus nuclear magnetic resonance (STNMR) has been applied to the rat kidney in vivo. The rate of renal metabolism determined by this method compares favorably with the renal oxygen consumption, assuming an ATP:oxygen ratio of 2. Hemorrhagic hypotension resulted in a 20% fall in renal blood flow and a significant fall in oxygen consumption. The rate of renal metabolism fell by 50%. This rate of ATP synthesis was below that required to maintain a normal [ATP], but renal [Pi] was not increased. When renal perfusion was reduced by 60%, intrarenal [Pi] rose. When [P1] was elevated, the method os STNMR no longer gave a reliable measure of the rate ATP synthesis, indicating that this new Pi pool was not in rapid chemical exchange with ATP. STNMR represents a useful noninvasive means of monitoring renal metabolic rate, with limitations due to insensitivity and the existence of multiple pools of intrarenal Pi.

  4. Ultrastructural localization of type V collagen in rat kidney

    PubMed Central

    1982-01-01

    Antibodies specific for the alpha 1 (V) chain and native collagen molecules containing the alpha 1 (V) chain have been used in electron immunohistochemical studies of rat kidney to determine the ultrastructural distribution of this class of collagen molecules. In addition, antibodies against type I collagen and whole basement membrane were used as markers for interstitial collagen and authentic basement membranes. Our results indicate that type V collagen is present in the renal interstitium in different forms: in close apposition to interstitial collagen fibers; in the stromal aspect of vascular basement membranes; and as particulate material not bound to other structures. On the basis of these findings, we postulate a binding or connecting function for this collagen type. PMID:7037794

  5. Demographics of the older adult and chronic kidney disease: a literature review.

    PubMed

    Elliott, Rowena W

    2012-01-01

    Older adults (65 years of age and older) comprised 4.1% of the population in 1900 (3.1 million), rose to 13.0% in 2010 (40.3 million), and are projected to reach 16.1% in 2020 (54.8 million). With each decade, there has been a steady increase, including older adults, in the population with chronic kidney disease. This article provides a review of the literature related to the demographics of the older adult population and older adults with chronic kidney disease. It also explores life expectancy, health promotion, and the economic impact of chronic kidney disease and its co-morbidities.

  6. Autoradiographic localization of benzodiazepine receptors in the rat kidney

    SciTech Connect

    Beaumont, K.; Healy, D.P.; Fanestil, D.D.

    1984-11-01

    The localization of benzodiazepine (BZD) receptors in the rat kidney was studied by autoradiography after in vitro labeling of kidney slices with flunitrazepam. The affinity, density, and rank order of displacement of (/sup 3/H)-flunitrazepam by several BZDs (RO 5-4864 > diazepam > clonazepam) demonstrated that binding was to BZD receptors of the peripheral type. In autoradiograms obtained with tritium-sensitive film, a high density of silver grains was obtained in the outer medulla, with lower densities in the cortex. Binding was absent from the inner medulla (papilla). In higher resolution autoradiograms obtained with an emulsion-coated cover slip procedure, silver grains were seen to be concentrated over a tubular element in both outer medulla and cortex, identifiable by morphology and distribution as the thick ascending limb of the loop of Henle and the distal convoluted tubule. The identity of the labeled tubules was confirmed by immunofluorescent localization in adjacent slices of Tamm-Horsfall protein, a specific marker for these segments of tubules. Investigation of the effects of peripherally specific BZDs such as RO 5-4864 on distal tubule function is indicated.

  7. Accumulation of Sulfate by Mitochondria of Rat Kidney Cortex

    PubMed Central

    Winters, Robert W.; Delluva, Adelaide M.; Deyrup, Ingrith J.; Davies, Robert E.

    1962-01-01

    Twice washed mitochondria from rat kidney cortex can accumulate sulfate ions from low (10-7 M) ambient concentrations to create virtual gradients of several hundred to one. This sulfate is subsequently released. The activation energy for the uptake is 12,000 calories per mole; for release it is about 30,000 calories per mole. Variations in the sulfate concentration of the medium show that there is a straight line Freundlich adsorption isotherm over a million-fold range of concentration of sulfate in the medium. There are 9 x 104 sites at 10-5 M and 9 x 105 sites at 10-3 M sulfate per average single mitochondrion. Preincubation at 30°C rapidly destroys the ability to accumulate sulfate. Partial protection occurs if oxidative phosphorylation is proceeding during the preincubation. The concentration of the endogenous inorganic sulfate of twice washed mitochondria is 4.2 x 10-4 moles per liter of mitochondrial pellet water; 99.85 per cent of this endogenous sulfate is inexchangeable with external sulfate in vitro. It is all exchangeable in vivo. The pH optimum for accumulation of radiosulfate from dilute external sulfate concentrations is 5.5. These observations show that there is a delicate and specific mechanism in mitochondria from kidney cortex which accumulates sulfate. The chemical nature of the accumulated sulfate is unknown. PMID:14007618

  8. Inadequate Antioxidative Responses in Kidneys of Brain-Dead Rats.

    PubMed

    Hoeksma, Dane; Rebolledo, Rolando A; Hottenrott, Maximilia; Bodar, Yves S; Wiersema-Buist, Janneke J; Van Goor, Harry; Leuvenink, Henri G D

    2017-04-01

    Brain death (BD)-related lipid peroxidation, measured as serum malondialdehyde (MDA) levels, correlates with delayed graft function in renal transplant recipients. How BD affects lipid peroxidation is not known. The extent of BD-induced organ damage is influenced by the speed at which intracranial pressure increases. To determine possible underlying causes of lipid peroxidation, we investigated the renal redox balance by assessing oxidative and antioxidative processes in kidneys of brain-dead rats after fast and slow BD induction. Brain death was induced in 64 ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Fast and slow inductions were achieved by an inflation speed of 0.45 and 0.015 mL/min, respectively, until BD confirmation. Healthy non-brain-dead rats served as reference values. Brain-dead rats were monitored for 0.5, 1, 2, or 4 hours, after which organs and blood were collected. Increased MDA levels became evident at 2 hours of slow BD induction at which increased superoxide levels, decreased glutathione peroxidase (GPx) activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased plasma creatinine levels were evident. At 4 hours after slow BD induction, superoxide, MDA, and plasma creatinine levels increased further, whereas GPx activity remained decreased. Increased MDA and plasma creatinine levels also became evident after 4 hours fast BD induction. Brain death leads to increased superoxide production, decreased GPx activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased MDA and plasma creatinine levels. These effects were more pronounced after slow BD induction. Modulation of these processes could lead to decreased incidence of delayed graft function.

  9. Effects of immunosuppressive treatment on protein expression in rat kidney

    PubMed Central

    Kędzierska, Karolina; Sporniak-Tutak, Katarzyna; Sindrewicz, Krzysztof; Bober, Joanna; Domański, Leszek; Parafiniuk, Mirosław; Urasińska, Elżbieta; Ciechanowicz, Andrzej; Domański, Maciej; Smektała, Tomasz; Masiuk, Marek; Skrzypczak, Wiesław; Ożgo, Małgorzata; Kabat-Koperska, Joanna; Ciechanowski, Kazimierz

    2014-01-01

    The structural proteins of renal tubular epithelial cells may become a target for the toxic metabolites of immunosuppressants. These metabolites can modify the properties of the proteins, thereby affecting cell function, which is a possible explanation for the mechanism of immunosuppressive agents’ toxicity. In our study, we evaluated the effect of two immunosuppressive strategies on protein expression in the kidneys of Wistar rats. Fragments of the rat kidneys were homogenized after cooling in liquid nitrogen and then dissolved in lysis buffer. The protein concentration in the samples was determined using a protein assay kit, and the proteins were separated by two-dimensional electrophoresis. The obtained gels were then stained with Coomassie Brilliant Blue, and their images were analyzed to evaluate differences in protein expression. Identification of selected proteins was then performed using mass spectrometry. We found that the immunosuppressive drugs used in popular regimens induce a series of changes in protein expression in target organs. The expression of proteins involved in drug, glucose, amino acid, and lipid metabolism was pronounced. However, to a lesser extent, we also observed changes in nuclear, structural, and transport proteins’ synthesis. Very slight differences were observed between the group receiving cyclosporine, mycophenolate mofetil, and glucocorticoids (CMG) and the control group. In contrast, compared to the control group, animals receiving tacrolimus, mycophenolate mofetil, and glucocorticoids (TMG) exhibited higher expression of proteins responsible for renal drug metabolism and lower expression levels of cytoplasmic actin and the major urinary protein. In the TMG group, we observed higher expression of proteins responsible for drug metabolism and a decrease in the expression of respiratory chain enzymes (thioredoxin-2) and markers of distal renal tubular damage (heart fatty acid-binding protein) compared to expression in the CMG

  10. Identification of bile acid-CoA: amino acid N-acyltransferase in rat kidney.

    PubMed Central

    Kwakye, J B; Johnson, M R; Barnes, S; Grizzle, W E; Diasio, R B

    1991-01-01

    A novel location of the bile-acid-conjugating enzyme bile acid-CoA:amino acid N-acyltransferase (BAT) has been discovered in the cytosolic fraction of rat kidney. Both taurine and glycine were utilized as substrates. Formation of bile acid N-acyl amidates was verified by h.p.l.c. by comparison with authentic standards and by specific hydrolysis using cholylglycine hydrolase. Immunoblot analysis using a human liver anti-BAT polyclonal antibody indicated that rat kidney BAT has the same molecular mass as rat liver BAT. These findings suggest that the kidney has a role in bile acid metabolism and physiology. Images Fig. 6. PMID:1764044

  11. Curative effect of sesame oil in a rat model of chronic kidney disease.

    PubMed

    Liu, Chuan-Teng; Chien, Se-Ping; Hsu, Dur-Zong; Periasamy, Srinivasan; Liu, Ming-Yie

    2015-12-01

    Chronic kidney disease causes a progressive and irreversible loss of renal function. We investigated the curative effect of sesame oil, a natural, nutrient-rich, potent antioxidant, in a rat model of chronic kidney disease. Chronic kidney disease was induced by subcutaneously injecting uni-nephrectomized rats with deoxycorticosterone acetate (DOCA) and 1% NaCl [DOCA/salt] in drinking water. Four weeks later, the rats were gavaged with sesame oil (0.5 or 1 mL/kg per day) for 7 days. Renal injury, histopathological changes, hydroxyl radical, peroxynitrite, lipid peroxidation, Nrf2, osteopontin expression, and collagen were assessed 24 h after the last dose of sesame oil. Blood urea nitrogen, creatinine, urine volume, and albuminuria were significantly higher in the DOCA/salt treated rats than in control rats. Sesame oil significantly decreased these four tested parameters in DOCA/salt treated rats. In addition, creatinine clearance rate and nuclear Nrf2 expression were significantly decreased in the DOCA/salt treated rats compared to control rats. Sesame oil significantly decreased hydroxyl radical, peroxynitrite level, lipid peroxidation, osteopontin, and renal collagen deposition, but increased creatinine clearance rate and nuclear Nrf2 expression in DOCA/salt treated rats. We conclude that supplementation of sesame oil mitigates DOCA/salt induced chronic kidney disease in rats by activating Nrf2 and attenuating osteopontin expression and inhibiting renal fibrosis in rats. © 2015 Asian Pacific Society of Nephrology.

  12. Neutrophil gelatinase-associated lipocalin in a triphasic rat model of adenine-induced kidney injury.

    PubMed

    Gil, Amnon; Brod, Vera; Awad, Hoda; Heyman, Samuel N; Abassi, Zaid; Frajewicki, Victor

    2016-10-01

    The aim of this study is to investigate whether NGAL, given its advantages over traditional biomarkers, can be used to describe the dynamic characteristics of the renal tubulointerstitial insult caused by adenine. Subsequently, it will be possible to assess NGAL as a biomarker of any acute kidney injury, on top of chronic interstitial disease, if NGAL levels are stable through the chronic phase of our adenine model. Study group rats were fed an adenine diet, and control group rats were fed a regular diet only. Blood and urine samples for urea, creatinine and NGAL were drawn from each rat at the beginning of the study and after 1, 3, 4, 5, 6, 7 and 8 weeks. Kidney slices from these rats were stained with Hematoxylin-eosin (HE) and β-actin stainings. Serum urea, creatinine and NGAL levels and urinary NGAL/creatinine ratio in the study group were higher than baseline and than in the control group; these differences were statistically significant in some of the intervals. Tubulointerstitial changes and adenine crystals were evident in the study group rats. In the rats fed adenine, serum urea, creatinine and NGAL levels and urinary NGAL/creatinine ratio followed a triphasic pattern of kidney injury: an acute phase while on the adenine diet, a partial recovery phase after switching to the regular diet and a chronic kidney disease phase after stabilization of renal function. NGAL can serve a biomarker for acute kidney injury and possibly for chronic kidney disease in the tubulointerstitial rat model.

  13. Indoxyl sulfate reduces klotho expression and promotes senescence in the kidneys of hypertensive rats.

    PubMed

    Adijiang, Ayinuer; Shimizu, Hidehisa; Higuchi, Yusuke; Nishijima, Fuyuhiko; Niwa, Toshimitsu

    2011-01-01

    Administration of indoxyl sulfate, a uremic toxin, promotes progression of chronic kidney disease in rats affected by the disease. Klotho, an anti-aging gene, is expressed in the kidneys, and its renal expression is decreased in chronic kidney disease. This study aimed to clarify whether indoxyl sulfate could reduce klotho expression and contribute to cell senescence in the kidneys of hypertensive rats. The rats used for this study were segregated in to the following 4 groups: (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive indoxyl sulfate-administered rats (DN + IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive indoxyl sulfate-administered rats (DH + IS). After 32 weeks, their kidneys were excised for histological and immunohistochemical analysis for klotho, senescence-associated β-galactosidase, p16(INK4a), p21(WAF1/CIP1), p53, and retinoblastoma protein (Rb). DH + IS rats showed decreased expression of klotho, increased expression of senescence-associated β-galactosidase, p16(INK4a), p21(WAF1/CIP1), p53, and Rb in renal tubular cells, and increased tubulointerstitial fibrosis and mesangial expansion as compared with DH rats. Further, DN + IS rats showed decreased expression of klotho as compared with DN rats. Administration of indoxyl sulfate to hypertensive rats reduced renal expression of klotho and promoted cell senescence with expression of senescence-related proteins, such as p16(INK4a), p21(WAF1/CIP1), p53, and Rb, which was accompanied by renal fibrosis. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  14. Study of rat kidney transamidinase structure and regulation with monoclonal antibodies and the purification and characterization of human kidney transamidinase

    SciTech Connect

    Gross, M.D.

    1985-01-01

    The isolation of monoclonal antibodies to transamidinase made possible the development of an immunosorbent inhibition assay for transamidinase protein using a /sup 125/I-labeled monoclonal antibody. This assay is a more direct measurement of transamidinase protein than the determination of the amount of polyclonal antibody required to precipitate the transamidinase activities. Rats were fed diets supplemented with creatine and/or glycine, and the amounts of transamidinase protein were determined with the assay using the monoclonal antibody. The transamidinase activities of kidneys from the rats fed the various supplemented diets ranged from 10 to 40% of the control values, whereas, the amounts of transamidinase protein were, in all instances no lower than 66% of the control values. Purified homogeneous rat kidney transamidinase and rat kidney supernatants were subjected to isoelectric focussing and four to five fractions of the enzyme were obtained. Polyclonal antibodies, but not the monoclonal antibodies were found by Western blotting experiments to recognize all the forms of the enzyme obtained by the isoelectric focussing. The author concluded that the monoclonal antibodies recognized forms of the enzyme that changed very little in amount, relative to the alterations in enzyme activities, when rats were fed a diet containing creatine.

  15. Specific cytotoxic T cells are found in the nonrejected kidneys of blood-transfused rats

    SciTech Connect

    Dallman, M.J.; Wood, K.J.; Morris, P.J.

    1987-02-01

    Preoperative, donor-specific blood transfusion leads to indefinite survival of rat renal allografts in the strain combinations used. /sup 51/Cr-release assays have shown that the level of specific cytotoxic effector activity in the grafts of transfused (nonrejected kidney) animals is very high and may equal or exceed that seen in the grafts of untreated (rejected kidney) recipients. Such cytotoxicity demonstrates specificity for the alloantigens of the kidney, is T cell-mediated, and may persist within the transplant.

  16. Developmental immunolocalization of heat shock protein 70 (HSP70) in epithelial cell of rat kidney.

    PubMed

    Kang, S-S; Song, J-H; Lee, M-Y; Kang, Y-H; Lim, S S; Ryu, S-Y; Jung, J-Y

    2011-11-01

    During renal development the cells in the medulla are exposed to elevated and variable interstitial osmolality. Heat shock protein 70 (HSP70) is a major molecular chaperone and plays an important role in the protection of cells in the renal medulla from high osmolality. The purpose of this study was to establish the time of immunolocalization and distribution of HSP70 in developing and adult rat kidney. In addition, changes in HSP70 immunolocalization following the infusion of furosemide were investigated. In adult animals, the HSP70 was expressed in the medullary thin ascending limb of Henle's loop (ATL) and inner medullary collecting duct (IMCD). In developing kidney, HSP70 immunoreactivity was first detected in the IMCD of the papillary tip on postnatal day 1. From four to 14 days of age, HSP70 was detected in the ATL after transformation from thick ascending limb, beginning at the papillary tip and ascending to the border between the outer and inner medulla. The immunolocalization of HSP70 in both the ATL and IMCD gradually increased during two weeks. The gradual increase in HSP70 was associated with an increase in its mRNA abundance. However, furosemide infusion resulted in significantly reduced HSP70 immunolocalization in the IMCD and ATL. These data demonstrated that the expression of HSP70 was closely correlated with changes in interstitial osmolality during the development of the kidney. We suggest that HSP70 protects ATL and IMCD cells in the inner medulla from the stress of high osmolality and may be involved in the transformation of the ATL of the long loop of Henle during renal development.

  17. Kidney dysfunction and cerebral microbleeds in neurologically healthy adults

    PubMed Central

    Kim, Sang Hyuck; Shin, Dong Wook; Yun, Jae Moon; Lee, Ji Eun; Lim, Jae-Sung; Cho, Be Long

    2017-01-01

    Introduction Cerebral microbleed (CMB) is a potent risk factor for overt cerebrovascular disease. Although some studies indicated the possible role of renal dysfunction as a risk factor of CMB, the findings could not be generalized. This study aimed to investigate the association between renal dysfunction and cerebral microbleed (CMB) in neurologically healthy adults. Materials and methods A total of 2,518 subjects who underwent brain MRI as part of health screening were involved in the study. CMBs were defined as well-demarcated focal areas of low signal intensity with associated blooming on the T2-weighted MRI measuring less than 5mm in diameter. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease formula. Kidney function was classified as normal (≥90), mild (60 to 89.9), moderate (30 to 59.9), and severe (<30 mL/min/1.73 m2) renal dysfunction according to the GFR. Results The mean age of the participants was 57.5 ± 8.3 years (ranged 40 to 79), and 1,367 subjects (54.3%) were male. The mean GFR level was 81.5 ± 15.5, and the prevalence of CMB was 4.1% (n = 103). Subjects with CMB demonstrated a higher proportion of moderate-to-severe renal dysfunction than those without CMB (15.5% vs. 5.0%, p < 0.001). In the multivariate logistic regression analysis, moderate-to-severe renal dysfunction showed a significant association with CMB (adjusted odd ratio = 2.63; p = 0.008). Furthermore, a decrease in the GFR level was associated with an increasing trend of the presence of CMB (p for trend = 0.031) and number of CMB lesions (p for trend = 0.003). Conclusions Renal dysfunction was significantly associated with the presence of CMB in neurologically healthy adults. More studies are needed to evaluate if treatment of kidney disease and risk factor modification may prevent further progress of CMB. PMID:28207801

  18. Regulation of ENaC trafficking in rat kidney

    PubMed Central

    Frindt, Gustavo; Gravotta, Diego

    2016-01-01

    The epithelial Na channel (ENaC) forms a pathway for Na+ reabsorption in the distal nephron, and regulation of these channels is essential for salt homeostasis. In the rat kidney, ENaC subunits reached the plasma membrane in both immature and fully processed forms, the latter defined by either endoglycosidase H–insensitive glycosylation or proteolytic cleavage. Animals adapted to a low-salt diet have increased ENaC surface expression that is specific for the mature forms of the subunit proteins and is similar (three- to fourfold) for α, β, and γENaC. Kidney membranes were fractionated using differential centrifugation, sucrose-gradient separation, and immunoabsorption. Endoplasmic reticulum membranes, isolated using an antibody against calnexin, expressed immature γENaC, and the content decreased with Na depletion. Golgi membranes, isolated with an antibody against the cis-Golgi protein GM130, expressed both immature and processed γENaC; Na depletion increased the content of processed γENaC in this fraction by 3.8-fold. An endosomal compartment isolated using an antibody against Rab11 contained both immature and processed γENaC; the content of processed subunit increased 2.4-fold with Na depletion. Finally, we assessed the content of γENaC in the late endocytic compartments indirectly using urinary exosomes. All of the γENaC in these exosomes was in the fully cleaved form, and its content increased by 4.5-fold with Na depletion. These results imply that stimulation of ENaC surface expression results at least in part from increased rates of formation of fully processed subunits in the Golgi and subsequent trafficking to the apical membrane. PMID:26880754

  19. Effect of sweetener and flavoring agent on oxidative indices, liver and kidney function levels in rats.

    PubMed

    Amin, Kamal A; Al-muzafar, Hessa M; Abd Elsttar, Adel H

    2016-01-01

    Food additives while attract consumers, improve quality, control weight and replace sugar, may affect seriously children and adults health. Here, we investigated the adverse effects of saccharin and methylsalicyltaes as sweetener and flavoring agent on lipid profile, blood glucose, renal, hepatic function and oxidative stress/antioxidants (lipid peroxidation, catalase and reduced glutathione in liver tissues). Saccharin and methylsalicylate were administered orally in young male albino rats at low and high dose for 30 days. Rats were divided into 5 groups, 1st control group, 2nd and 3rd (low and high saccharin-treated groups) and 4th and 5th (low and high methylsalicylate-treated group). Serum total cholesterol, triglyceride, glucose levels and body weight gain were found decreased in saccharin high dose group compared to control. Rats consumed high dose of saccharin showed a significant decrease in serum triglycerides, cholesterol and LDL levels. Low and high doses of saccharin exhibited a significant increase in liver function marker of ALT, AST, ALP activity, total proteins and albumin levels and renal function test (urea and creatinine levels) in comparison with control group. Further, saccharin at high dose induced significant decrease in liver GSH levels, catalase and SOD activity and increase in hepatic MDA level. Overall saccharin harmfully altered biochemical markers in liver and kidney at higher as well as lower doses. Whereas, methyl salicylates did not pose a risk for renal function and hepatic oxidative markers.

  20. Effects of nutrition and alcohol on the microsomal monooxygenase system (MMS) of rat kidney

    SciTech Connect

    Ronis, M.; Huang, J.; Ingelman-Sundberg, M.; Badger, T.M. Arkansas Children's Hospital Research Center, Little Rock )

    1991-03-15

    Ethanol is a known inducer of the hepatic cytochrome P450 dependent microsomal monooxygenase system (MMS). As a consequence, ethanol intake affects the clearance and metabolism of many drugs and other xenobiotics including acetaminophen, enflurane, carbon tetrachloride and ethanol itself. The major ethanol inducible cytochrome P450 isozyme in the rat liver, CYP 2E1, has been well characterized. Much less is known concerning extrahepatic effects of ethanol on the monooxygenase system. In the current study, the effects of diet and alcohol were examined on MMS activities and cytochrome P450 expression in the kidneys of adult male Sprague-Dawley rats. Three diets containing no ethanol and two diets containing ethanol at 35% of total calories were studied. Renal MMS activities were measured using enzyme specific substrates and isozyme apoprotein levels were determined by Western blot analysis using antibodies directed against rat hepatic cytochrome P450s CYP 2E1, CYP 2A1 and CYP 3A2. Several diet and alcohol induced effects were observed, including a 5-fold diet-independent ethanol induction of CYP 2E1 cross reactive protein. No diet or ethanol effects were observed in levels of CYP 2A1 or CYP 3A2 cross reactive proteins.

  1. Azilsartan improves glycemic status and reduces kidney damage in zucker diabetic fatty rats.

    PubMed

    Hye Khan, Md Abdul; Neckář, Jan; Haines, Jasmine; Imig, John D

    2014-08-01

    Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, demonstrates antihypertensive and organ protective effects in hypertension. We investigated the efficacy of AZL-M to ameliorate metabolic syndrome and kidney damage associated with type 2 diabetes using Zucker diabetic fatty (ZDF) rats. ZDF rats were treated with vehicle or AZL-M for 8 weeks. Zucker diabetic lean (ZDL) rats were used as controls. Urine and plasma samples were collected for biochemical analysis, and kidney tissues were used for histopathological and immunohistopathological examination at the end of the 8-week protocol. ZDF rats were diabetic with hyperglycemia and impaired glucose tolerance, and AZL-M ameliorated the diabetic phenotype. ZDF rats were hypertensive compared with ZDL rats (181±6 vs. 129±7mm Hg), and AZL-M decreased blood pressure in ZDF rats (116±7mm Hg). In ZDF rats, there was marked renal damage with elevated proteinuria, albuminuria, nephrinuria, 2-4-fold higher tubular cast formation, and glomerular injury compared with ZDL rats. AZL-M treatment reduced renal damage in ZDF rats. ZDF rats demonstrated renal inflammation and oxidative stress with elevated urinary monocyte chemoattractant protein 1 excretion, renal infiltration of macrophages, and elevated kidney malondialdehyde levels. AZL-M reduced oxidative stress and inflammation in ZDF rats. Overall, we demonstrate that AZL-M attenuates kidney damage in type 2 diabetes. We further demonstrate that anti-inflammatory and antioxidative activities of AZL-M contribute to its kidney protective action. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Ontogenic development of antidiuretic hormone receptors in rat kidney: comparison of hormonal binding and adenylate cyclase activation.

    PubMed

    Rajerison, R M; Butlen, D; Jard, S

    1976-03-01

    The development of adenylate cyclase responsiveness to vasopressin and parathyroid hormone was studied using membrane fractions prepared from medullo-papillary and cortical portions of kidneys of 2-46-day-old rats. The development of vasopressin binding capacity was followed on the same preparations, using [3H]vasopressin. The characteristics of medullo-papillary adenylate cyclase response to vasopressin were identical in young and adult control animals as regards apparent Km values for [Lys8]vasopressin (3 X 10(-8) M), specificity towards the natural neurohypophysial peptides and the effects of Mg2+. However, the magnitude of maximal enzyme activation by vasopressin was much lower in very young than adult animals. Accordingly vasopressin responsiveness increased sharply between the 10th and 25th days but the magnitude of the maximal response only reached the adult value between the 30th and 45th days after birth. During both periods basal adenylate cyclase activity was almost independent of age. Specific vasopressin binding sites were detected on kidney medullo-papillary membranes from young animals. Vasopressin binding capacity and adenylate cyclase responsiveness to the hormone followed similar development patterns. However, the appearance of specific binding sites slightly preceded the onset of adenylate cyclase responsiveness. Basal cortical adenylate cyclase activity/mg protein was 12 times higher in 2-day-old rats than in the adult controls. It dropped with age but only fell to the adult value between the 25th and the 35th days after birth. For the youngest animals tested (2 days old), the increase in activity due to parathyroid hormone was about half the increase measured in adults, and gradually rose to about 75% of the adult response between the 2nd and 46th days after birth. Apparent Km values for parathyroid hormone were identical in young and adult animals (3.2 and 3.0 U/ml, respectively).

  3. Salivary Alterations in Rats with Experimental Chronic Kidney Disease

    PubMed Central

    Romero, Ana Carolina; Bergamaschi, Cassia Toledo; de Souza, Douglas Nesadal; Nogueira, Fernando Neves

    2016-01-01

    Objective This study aimed to analyze changes in saliva composition and salivary secretion process of rats with chronic kidney disease induced by 5/6 nephrectomy to set the foundation for salivary studies related to CKD. Methods CKD was induced in Wistar rats via 5/6 nephrectomy. Blood and saliva samples were collected from Control, Sham and CKD groups at 8 and 12 weeks after the surgery. Salivation was stimulated via intraperitoneal injections of pilocarpine (1.0 mg/Kg body weight) or isoproterenol (5.0 mg/Kg body weight). Saliva was collected and immediately stored at -80°C until analysis. The salivary flow rate, total protein, amylase and peroxidase activities, and urea concentrations were measured. The blood urea nitrogen (BUN) and serum creatinine concentrations were also evaluated. Results Increases in BUN and serum creatinine concentrations were observed in the CKD groups. Amylase activity was significantly reduced in response to both stimuli in the CKD groups at 8 weeks and increased in the CKD groups at 12 weeks in response to isoproterenol stimulus. The peroxidase activities of the CKD groups were significantly reduced in response to isoproterenol stimulation and were increased at 12 weeks in response to pilocarpine stimulation. Salivary urea was significantly increased in the CKD groups at 8 weeks in response to the isoproterenol stimuli and at 12 weeks in response to both salivary agonists. Conclusions The pattern of alterations observed in this experimental model is similar to those observed in patients and clearly demonstrates the viability of 5/6 nephrectomy as an experimental model in future studies to understand the alterations in salivary compositions and in salivary glands that are elicited by CKD. PMID:26859883

  4. Effect of thiamine hydrochloride on lead induced lipid peroxidation in rat liver and kidney.

    PubMed

    Senapati, S K; Dey, S; Dwivedi, S K; Patra, R C; Swarup, D

    2000-08-01

    Thiamine hydrochloride was studied on lead-induced endogenous lipid peroxidation in rat hepatic and renal tissues following po doses of 2.73 mg lead/kg bw for 6 w. Simultaneous use of 25 mg thiamine hydrochloride/kg bw po reduced lead accumulation in liver and kidneys. There were significant decreases in endogenous lipid peroxide in liver and kidney from thiamine hydrochloride-treated rats. Histopathological lesions in thiamine-treated livers and kidneys were milder in comparison to lesions in untreated Pb-exposed animals. This indicates the prophylactic potential of thiamine for lead-induced lipid peroxidation.

  5. Antioxidant effects of maslinic acid in livers, hearts and kidneys of streptozotocin-induced diabetic rats: effects on kidney function.

    PubMed

    Mkhwanazi, Blessing N; Serumula, Metse R; Myburg, Rene B; Van Heerden, Fanie R; Musabayane, Cephas T

    2014-04-01

    Studies indicate that hyperglycemia-induced oxidative stress triggers the development of microvascular and macrovascular complications in diabetes. Accordingly, we hypothesized that maslinic acid (MA) prevents these complications due to its antioxidant properties. We, therefore, investigated the effects of 5-week MA treatment of streptozotocin (STZ)-induced diabetic rats on anti-oxidative status of cardiac, hepatic and renal tissues as well as on kidney function. Proximal tubular effects of MA were studied in anesthetized rats challenged with hypotonic saline after a 3.5 h equilibration for 4 h of 1 h control, 1.5 h treatment and 1.5 h recovery periods using lithium clearance. MA was added to the infusate during the treatment period. Oral glucose tolerance responses to MA were monitored in rats given a glucose load after an 18 h fast. Compared with untreated diabetic rats, MA-treated diabetic animals exhibited significantly low malondialdehyde (MDA, a marker of lipid peroxidation) and increased the activity of antioxidant enzymes; superoxide dismutase and glutathione peroxidase in hepatic, cardiac and renal tissues. The expressions of gastrocnemius muscle GLUT4 and kidney GLUT1 and GLUT2 were assessed to elucidate the mechanism of the hypoglycemic effects of MA. MA-treatment diminished the expression of GLUT1 and GLUT2 in diabetic kidney and reduced glycemia values of diabetic rats. MA administration increased urinary Na+ outputs and additionally the FENa indicating that at least part of the overall reduction in Na+ reabsorption occurred in the proximal tubules. These results suggest antioxidant effects of MA can ameliorate oxidative stress and improve kidney function in diabetes mellitus.

  6. Effects of prenatal 900 MHz electromagnetic field exposures on the histology of rat kidney.

    PubMed

    Ulubay, Mahmut; Yahyazadeh, Ahmad; Deniz, Ö Gülsüm; Kıvrak, Elfide Gizem; Altunkaynak, B Zuhal; Erdem, Gülünar; Kaplan, Süleyman

    2015-01-01

    To research the harmful effects of prenatal exposure of 900 megahertz (MHz) electromagnetic field (EMF) on kidneys of four-week-old male rats and to determine protective effects of melatonin (MEL) and omega-3 (ω-3). Twenty-one Wistar albino rats were randomly placed into seven groups as follows: Control (Cont), Sham, MEL, ω-3, EMF, EMF+ MEL and EMF+ω-3. After mating, three groups (EMF, EMF+ MEL, EMF+ ω-3) were exposed to an EMF. In the fourth week subsequent to parturition, six rats were randomly chosen from each group. Mean volume of kidneys and renal cortices, the total number of glomeruli and basic histological structure of kidney were evaluated by stereological and light microscopical methods, respectively. Stereological results determined the mean volume of the kidneys and cortices were significantly increased in EMF-exposed groups compared to the Cont group. However, EMF-unexposed groups were not significantly modified compared to the Cont group. Additionally, the total number of glomeruli was significantly higher in EMF-unexposed groups compared to the Cont group. Alternatively, the number of glomeruli in EMF-exposed groups was decreased compared to the Cont group. Prenatal exposure of rat kidneys to 900 MHz EMF resulted in increased total kidney volume and decreased the numbers of glomeruli. Moreover, MEL and ω-3 prevented adverse effects of EMF on the kidneys.

  7. Immunohistological observations in rat kidney allografts after local steroid administration

    PubMed Central

    1987-01-01

    In this report we investigated local regulatory mechanisms in graft rejection and their response to local immunosuppressive therapy. For this purpose local immunosuppression was induced in rat kidney allografts by intrarenal infusion of prednisolone. Intrarenal drug delivery resulted in high drug levels within the graft and low systemic drug levels. Systemic drug levels were by themselves not sufficiently immunosuppressive to induce graft survival, and local prednisolone levels within the graft proved to be responsible for prolongation of graft survival. During intrarenal drug delivery, systemic responsiveness to the renal allograft proved normal, since intrarenally treated grafts were infiltrated by MHC class II-positive host cells and, except for a somewhat lower percentage of macrophages, cellular infiltration in intrarenal treated grafts was comparable to untreated grafts. However, T cells and macrophages present in intrarenally treated grafts were not able to destroy the grafted tissue. Local immunosuppressive therapy resulted in inhibition of IL-2-R expression, absence of IFN-gamma, and prevention of MHC class II induction on grafted tissue. These observations strongly indicate the presence of local regulatory mechanisms in graft rejection. The experimental model described can be used for further analysis of these intragraft events. Moreover, the results demonstrate that local immunosuppressive therapy can contribute to effective inhibition of cellular immune response in graft rejection. PMID:3119756

  8. Renal accumulation of /sup 99m/Tc-DMSA in the artificially perfused isolated rat kidney

    SciTech Connect

    Goldraich, N.P.; Alvarenga, A.R.; Goldraich, I.H.; Ramos, O.L.; Sigulem, D.

    1985-12-01

    In order to investigate aspects of the renal handling of /sup 99m/Tc-DMSA, 68 isolated rat kidneys were artificially perfused. The experimental groups were: Group 1 (no. = 32)-oxygenated filtering kidneys; Group 2 (no. = 29)-oxygenated non-filtering kidneys; Group 3 (no. = 7)-anaerobic non-filtering kidneys. The authors conclude that the /sup 99m/Tc-DMSA complex is strongly bound to albumin, is not filtered and is removed from perfusion fluid through the renal peritubular capillary route and that this occurs by an active process which depends upon aerobic metabolism. This process has a high capacity and is not inhibited by probenecid.

  9. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats.

    PubMed

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M

    2015-05-01

    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats.

  10. Betanin attenuates oxidative stress and inflammatory reaction in kidney of paraquat-treated rat.

    PubMed

    Tan, Dehong; Wang, Yiheng; Bai, Bing; Yang, Xuelian; Han, Junyan

    2015-04-01

    The effects of natural pigment betanin on oxidative stress and inflammation in kidney of paraquat-treated rat were investigated. Paraquat was injected intraperitoneally into rats to induce renal damage. The rats were randomly divided into four groups: a control group, a paraquat group, and two paraquat groups that were treated with betanin at 25 and 100 mg/kg/d three days before and two days after paraquat administration. Treatment with betanin alleviated the paraquat-incurred acute kidney injury, evidenced by histological improvement, reduced serum and urine markers for kidney injury. Betanin antagonized the paraquat-induced inflammation, indicated by reduced expression of inducible nitric oxide synthase and cyclooxygenase, blunted activation of nuclear factor kappa B, and diminished lysosomal protease activities. Betanin also decreased oxidative stress elicited by paraquat. In conclusion, betanin may have a protective effect against paraquat-induced acute kidney damage. The mechanisms of the protection appear to be the inhibition of oxidative stress and inflammation.

  11. An oral sorbent, AST-120, increases Klotho expression and inhibits cell senescence in the kidney of uremic rats.

    PubMed

    Adijiang, Ayinuer; Niwa, Toshimitsu

    2010-01-01

    Klotho, an anti-aging gene, is primarily expressed in the kidney, and its renal expression is decreased in chronic renal failure (CRF). We determined if administration of an oral sorbent, AST-120, increases the expression of Klotho, and inhibits cell senescence in the kidney of CRF rats. CRF rats were produced by 4/5-nephrectomy. AST-120 was administered to the CRF rats at a dose of 4 g/kg with powder chow for 16 weeks, whereas powder chow alone was administered to control CRF rats. The expression of Klotho and cell senescence (senescence-associated beta-galactosidase: SA-beta-gal) was detected by immunohistochemistry. The expression of Klotho was significantly decreased in the kidney of CRF rats as compared with normal rats. AST-120-treated CRF rats showed significantly increased renal expression of Klotho as compared with CRF rats. The expression of SA-beta-gal was significantly increased in the kidney of CRF rats as compared with normal rats. AST-120-treated CRF rats showed significantly decreased expression of SA-beta-gal in the kidney as compared with CRF rats. AST-120 significantly decreased serum and urine levels of indoxyl sulfate. AST-120 increased Klotho expression, and inhibited cell senescence in the kidney of CRF rats, probably by alleviating indoxyl sulfate overload on the kidney. Copyright (c) 2009 S. Karger AG, Basel.

  12. Sexual dimorphism in development of kidney damage in aging Fischer-344 rats.

    PubMed

    Sasser, Jennifer M; Akinsiku, Oladele; Moningka, Natasha C; Jerzewski, Katie; Baylis, Chris; LeBlanc, Amanda J; Kang, Lori S; Sindler, Amy L; Muller-Delp, Judy M

    2012-08-01

    Aging kidneys exhibit slowly developing injury and women are usually protected compared with men, in association with maintained renal nitric oxide. Our purpose was to test 2 hypotheses: (1) that aging intact Fischer-344 (F344) female rats exhibit less glomerular damage than similarly aged males, and (2) that loss of female ovarian hormones would lead to greater structural injury and dysregulation of the nitric oxide synthase (NOS) system in aging F344 rat kidneys. We compared renal injury in F344 rats in intact, ovariectomized, and ovariectomized with estrogen replaced young (6 month) and old (24 month) female rats with young and old intact male rats and measured renal protein abundance of NOS isoforms and oxidative stress. There was no difference in age-dependent glomerular damage between young or old intact male and female F344 rats, and neither ovariectomy nor estrogen replacement affected renal injury; however, tubulointerstitial injury was greater in old males than in old females. These data suggest that ovarian hormones do not influence these aspects of kidney aging in F344 rats and that the greater tubulointerstitial injury is caused by male sex. Old males had greater kidney cortex NOS3 abundance than females, and NOS1 abundance (alpha and beta isoforms) was increased in old males compared with both young males and old females. NOS abundance was preserved with age in intact females, ovariectomy did not reduce NOS1 or NOS3 protein abundance, and estrogen replacement did not uniformly elevate NOS proteins, suggesting that estrogens are not primary regulators of renal NOS abundance in this strain. Nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production and nitrotyrosine immunoreactivity were increased in aging male rat kidneys compared with females, which could compromise renal nitric oxide production and/or bioavailability. The kidney damage expressed in aging F344 rats is fairly mild and is not related to loss of renal cortex NOS3

  13. Modifier loci in non-mutant, female Wistar Kyoto rats influence cellular pathogenesis of nephronophthisis in Lewis polycystic kidney rats.

    PubMed

    Yengkopiong, Jada Pasquale; Lako, Joseph Daniel Wani

    2015-09-01

    Genetic modifier loci influence the inheritance of diseases and lead to variability in phenotype progression. We report the influence of modifier loci in female Wistar Kyoto (WKY) rats on cellular pathogenesis of nephronophthisis inherited from Lewis polycystic kidney (LPK) rats. The loci modified cellular expression and progression of nephronophthisis in the backcross 1 (BC1) progeny. Mating experiments to produce BC1 progeny were carried out between three male LPK and seven female WKY rats. Fifteen female rats from the F1 generation were mated with the male LPK rats to produce the BC1 progeny. The rats with cystic kidney disease were identified and histology of the kidneys was carried out. Mapping studies and linkage analysis were carried out to identify the modifier loci. The BC1 progeny were less affected than the LPK strain with respect to disease severity and progression of the kidneys to end stage renal disease. It was found that the mean values of all the disease phenotypes of the mutant BC1 progeny were significantly different from those of the LPK rats, and these segregated with the genotypes of the markers located on chromosomes 5q34-q36 and 7q11-q34, giving maximum LOD scores greater than 3 (p < 0.001).

  14. Tangzhiqing Granules Alleviate Podocyte Epithelial-Mesenchymal Transition in Kidney of Diabetic Rats.

    PubMed

    Xu, Haiyan; Wang, Xu; Liu, Mingming; He, Xueyuan

    2017-01-01

    This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured. The kidney tissues were observed under light microscope and transmission electron microscopy. To search for the underlying mechanism, we examined the epithelial-to-mesenchymal transition (EMT) related molecular markers and TGF-β/smad signaling pathway key proteins expression. The results showed that Tangzhiqing granules relieved the structural damage and functional changes of diabetic kidneys. Kidney podocyte EMT related molecular markers nephrin and CD2AP expression were increased, when desmin and α-SMA levels were decreased by Tangzhiqing granules in diabetic rats. Further TGF-β/smad signaling pathway key proteins TGF-β1 and p-smad2/3 levels were decreased in diabetic rats after treatment with Tangzhiqing granules. These findings suggest that Tangzhiqing granules may protect the podocytes of diabetic nephropathy rats via alleviating podocyte EMT and likely activating TGFβ/smad signaling pathway.

  15. Tangzhiqing Granules Alleviate Podocyte Epithelial-Mesenchymal Transition in Kidney of Diabetic Rats

    PubMed Central

    Xu, Haiyan; Liu, Mingming; He, Xueyuan

    2017-01-01

    This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured. The kidney tissues were observed under light microscope and transmission electron microscopy. To search for the underlying mechanism, we examined the epithelial-to-mesenchymal transition (EMT) related molecular markers and TGF-β/smad signaling pathway key proteins expression. The results showed that Tangzhiqing granules relieved the structural damage and functional changes of diabetic kidneys. Kidney podocyte EMT related molecular markers nephrin and CD2AP expression were increased, when desmin and α-SMA levels were decreased by Tangzhiqing granules in diabetic rats. Further TGF-β/smad signaling pathway key proteins TGF-β1 and p-smad2/3 levels were decreased in diabetic rats after treatment with Tangzhiqing granules. These findings suggest that Tangzhiqing granules may protect the podocytes of diabetic nephropathy rats via alleviating podocyte EMT and likely activating TGFβ/smad signaling pathway. PMID:28163747

  16. Perfluoroalkyl Chemicals and Chronic Kidney Disease in US Adults

    PubMed Central

    Shankar, Anoop; Xiao, Jie; Ducatman, Alan

    2011-01-01

    Chronic kidney disease (CKD) is a major public health problem. Identifying novel risk factors for CKD, including widely prevalent environmental exposures, is therefore important. Perfluoroalkyl chemicals (PFCs), including perfluorooctanoic acid and perfluorooctane sulfonate, are manmade chemicals that have been detected in the blood of more than 98% of the US population. Results from experimental animal studies have suggested that an association between PFCs and CKD is plausible. However, in humans, the relation between serum PFCs and CKD has not been examined. The authors examined the relation of serum PFCs and CKD in 4,587 adult participants (51.1% women) from the combined 1999–2000 and 2003–2008 cycles of the National Health and Nutritional Examination Survey for whom PFC measurements were available. The main outcome was CKD, defined as a glomerular filtration rate of less than 60 mL/minute/1.73 m2. The authors found that serum levels of PFCs, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with CKD. This association was independent of confounders such as age, sex, race/ethnicity, body mass index, diabetes, hypertension, and serum cholesterol level. Compared with subjects in quartile 1 (referent), the multivariable odds ratio for CKD among subjects in quartile 4 was 1.73 (95% confidence interval: 1.04, 2.88; P for trend = 0.015) for perfluorooctanoic acid and 1.82 (95% confidence interval: 1.01, 3.27; P for trend = 0.019) for perfluorooctane sulfonate. The present results suggest that elevated PFC levels are associated with CKD. PMID:21873601

  17. Permanent catheterization of the carotid artery induces kidney infection and inflammation in the rat.

    PubMed

    Fonseca, Uno N K; Nielsen, Sanne Gram; Hau, Jann; Hansen, Axel Kornerup

    2010-01-01

    Catheterization of the carotid artery and the jugular vein is one of the most commonly applied techniques used to gain intravascular access in pharmacology studies on rodents. We catheterized 10 rats by conventional clean techniques, 10 rats by aseptic techniques and 10 rats by conventional clean techniques using a heparin-coated catheter rather than an ordinary non-coated polyvinyl chloride catheter. In all groups, approximately 80% of the rats developed kidney infection and 10-30% of the rats were septicaemic. Clinical chemistry did not indicate severe kidney damage, but serum haptoglobin and body temperature rises indicated an inflammatory response in rats independent of the surgical method. Heparin coating did not seem to improve the usability of the catheter. It is concluded that this commonly used method for catheterization has an impact on animals that may very well render them unsuitable for the purpose, e.g. pharmacological research, and therefore an alternative method would be preferable.

  18. EFFECTS OF SALVIA MILTIORRHIZAE ON THE KIDNEY OF RATS WITH SEVERE ACUTE PANCREATITIS AND OBSTRUTIVE JAUNDICE.

    PubMed

    Guibing, Ren; Xiping, Zhang; Xiaowen, Ding; Dehong, Zou; Hongjiang, Yang; Xiaoru, Meng; Wenju, Mo; Xiangming, He; Shuai, Zhao

    2017-01-01

    Severe acute pancreatitis (SAP) and obstructive jaundice (OJ) are frequent recurring diseases that bring about huge threat to human health. Some reports have demonstrated that Salviae miltiorrhizae can protect multiple organs of SAP and OJ model animals or patients, but their related mechanisms were not clear. In this study, we observed the effects of Salvia miltiorrhizae injection on apoptosis and NF-κB expression in kidney and explored the protective effect and mechanism of Salvia miltiorrhizae on the kidney of SAP or OJ rats. The results obtained will provide a theoretical basis for clinical application of Salvia miltiorrhizae. A total of 288 rats were used for SAP -and OJ-associated experiments. The mortality rates of rats, the contents of serum BUN and CREA, the expression levels of Bax, NF-κB proteins and the apoptosis index were observed, respectively. The pathological changes in the kidney of SAP or OJ rats in treated group were mitigated to varying degrees. At 6 and 12 hours after operation in SAP rats or on 21 and 28 days after operation in OJ rats, the contents of serum CREA in treated group were significantly lower than those in model control group; At 3 and 6 hours after operation, the staining intensity of Bax protein of kidney in treated group was significantly lower than that in model control group; on 14 days after operation, the apoptosis index in the kidney of OJ rats in treated group was significantly lower than that in model control group. Salvia miltiorrhizae can exert protective effects on the kidney of SAP and OJ rats.

  19. Effect of bis-1,4-dihydropyridine in the kidney of diabetic rats.

    PubMed

    Gómez-Pliego, Raquel; Gómez-Zamudio, Jaime; Velasco-Bejarano, Benjamín; Ibarra-Barajas, Maximiliano; Villalobos-Molina, Rafael

    2013-01-01

    The in vivo effectiveness of 4-dihydropyridine (bis-1,4-DHP), a new calcium-channel blocker, as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. Diabetes in male Wistar rats, control, diabetic, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP, was induced by a single administration of STZ (55 mg·kg(-1), i.p.). In the drug-treated groups, treatment with bis-1,4-DHP (10 mg·kg(-1)·day(-1)) started one week before diabetes induction; bis-1,4-DHP was dissolved in DMSO (0.3%) and suspended in drinking water with carboxymethyl cellulose (3%). Parameters evaluated were body weight, blood glucose, albuminuria, proteinuria, creatinine, urea excretion, kidney's weight / body weight ratio, and kidney perfusion pressure in all rat groups at different times of diabetes (2, 4, 6, and 10 weeks). Kidney weight of diabetic rats significantly increased vs. control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats at different times of diabetes. The ratios % kidney weight / 100 g body weight were different between control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats vs. diabetic rats (P < 0.05). Kidney perfusion pressure was decreased by diabetes, while it was partially recovered by bis-1,4-DHP treatment in response to phenylephrine. Bis-1,4-DHP had a tendency to decrease hyperglycemia vs. diabetic rats, even though glycemia was too high as compared with controls, and it ameliorated albuminuria, creatinine, and urea excretion, suggesting a favorable effect on renal haemodynamics. Bis-1,4-DHP, by inhibiting Ca(2+) entrance, induced vasodilation in renal vascular bed and thus may have a nephroprotective effect against diabetes-induced renal dysfunction, but does not have significant impact on hyperglycemia.

  20. Kidney biomarkers in MCPA-induced acute kidney injury in rats: reduced clearance enhances early biomarker performance.

    PubMed

    Wunnapuk, Klintean; Liu, Xin; Gobe, Glenda C; Endre, Zoltan H; Peake, Philip W; Grice, Jeffrey E; Roberts, Michael S; Buckley, Nicholas A

    2014-03-21

    For improved early detection and assessment of severe acute kidney damage following accidental or intentional ingestion of the herbicide MCPA, we compared a panel of 14 novel kidney injury biomarkers with plasma creatinine. Male Wistar rats received four different oral doses of MCPA and plasma and urine biomarker levels were measured at 8, 24 and 48 h after MCPA exposure. Diagnostic performances using absolute levels, urine levels normalized to urine creatinine or urinary excretion rate were determined by ROC analysis. Plasma creatinine remained the best early biomarker for predicting histological changes at 48 h. The performance of plasma cystatin C in mirroring kidney function was similar to that of plasma creatinine. While urine concentrations were generally less predictive, normalization by urine creatinine greatly improved the performance of several biomarkers. This may be due to an apparent amplification of the biomarker signal on normalizing to creatinine, in the presence of a declining glomerular filtration rate prior to reaching steady state. Normalized 8 h osteopontin and albumin concentrations outperformed other normalized biomarkers in predicting histological changes at later times. Normalized urinary kidney injury molecule-1 at 48 h also correlated well with the degree of kidney damage.

  1. Dietary phosphate restriction ameliorates endothelial dysfunction in adenine-induced kidney disease rats

    PubMed Central

    Van, Tan Vu; Watari, Eriko; Taketani, Yutaka; Kitamura, Tomoyo; Shiota, Asuka; Tanaka, Terumi; Tanimura, Ayako; Harada, Nagakatsu; Nakaya, Yutaka; Yamamoto, Hironori; Miyamoto, Ken-ichi; Takeda, Eiji

    2012-01-01

    Hyperphosphatemia causes endothelial dysfunction as well as vascular calcification. Management of serum phosphate level by dietary phosphate restriction or phosphate binders is considered to be beneficial to prevent chronic kidney disease patients from cardiovascular disease, but it has been unclear whether keeping lower serum phosphate level can ameliorate endothelial dysfunction. In this study we investigated whether low-phosphate diet can ameliorate endothelial dysfunction in adenine-induced kidney disease rats, one of useful animal model of chronic kidney disease. Administration of 0.75% adenine-containing diet for 21 days induced renal failure with hyperphosphatemia, and impaired acetylcholine-dependent vasodilation of thoracic aortic ring in rats. Then adenine-induced kidney disease rats were treated with either control diet (1% phosphate) or low-phosphate diet (0.2% phosphate) for 16 days. Low-phosphate diet ameliorated not only hyperphosphatemia but also the impaired vasodilation of aorta. In addition, the activatory phosphorylation of endothelial nitric oxide synthase at serine 1177 and Akt at serine 473 in the aorta were inhibited by in adenine-induced kidney disease rats. The inhibited phosphorylations were improved by the low-phosphate diet treatment. Thus, dietary phosphate restriction can improve aortic endothelial dysfunction in chronic kidney disease with hyperphosphatemia by increase in the activatory phosphorylations of endothelial nitric oxide synthase and Akt. PMID:22798709

  2. Feeding flaxseed oil but not secoisolariciresinol diglucoside results in higher bone mass in healthy rats and rats with kidney disease.

    PubMed

    Weiler, H A; Kovacs, H; Nitschmann, E; Bankovic-Calic, N; Aukema, H; Ogborn, M

    2007-05-01

    Flaxseed's oil and lignan, secoisolariciresinol diglucoside (SDG), are implicated in attainment of health and treatment of renal injury and osteoporosis. To test for these benefits, weanling Han:SPRD-cy rats (n=171) with or without kidney disease were randomized to diets made with either corn oil or flaxseed oil and with or without SDG for 12 weeks. In females, weight was lower with the SDG diet. In males fed flaxseed oil, lean mass was higher and fat % was lower. In both sexes, fat % was lower in diseased rats. Bone mineral content (BMC) and density were higher in rats fed flaxseed oil and lower in diseased rats, additionally; BMC was lower in SDG-supplemented females. The benefit of flaxseed oil on body composition is sex specific but the effect on bone mass is not. Lastly, reduced weight due to early rat kidney disease is not due to loss of lean body mass.

  3. Fenofibrate Attenuates Hypertension in Goldblatt Hypertensive Rats: Role of 20-Hydroxyeicosatetraenoic Acid in the Nonclipped Kidney.

    PubMed

    Sporková, Alexandra; Čertíková Chábová, Věra; Doleželová, Šárka; Jíchová, Šárka; Kopkan, Libor; Vaňourková, Zdeňka; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Maxová, Hana; Červenka, Luděk

    2017-06-01

    There is vast evidence that the renin-angiotensin system is not the sole determinant of blood pressure (BP) elevation in human renovascular hypertension or the relevant experimental models. This study tested the hypothesis that kidney deficiency of 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway of arachidonic acid metabolism, is important in the pathophysiology of the maintenance phase of 2-kidney, 1-clip (2K1C) Goldblatt hypertension. In 2K1C Goldblatt rats with established hypertension, angiotensin II, angiotensin 1-7, 20-HETE concentrations and gene expression of CYP4A1 enzyme (responsible for 20-HETE formation) of the nonclipped kidney were determined. We examined if 14 days׳ administration of fenofibrate, a lipid-lowering drug, would increase CYP4A1 gene expression and renal 20-HETE formation, and if increased 20-HETE concentrations in the nonclipped kidney would decrease BP (telemetric measurements). CYP4A1 gene expression, 20-HETE and angiotensin 1-7 concentrations were lower and angiotensin II levels were higher in the nonclipped kidney of 2K1C rats than in sham-operated rats. Fenofibrate increased CYP4A1 gene expression and 20-HETE concentration in the nonclipped kidney and significantly decreased BP in 2K1C rats but did not restore it to normotensive range. The treatment did not change BP in sham-operated rats. Our results suggest that alterations in the RAS and CYP-dependent ω-hydroxylase metabolites of arachidonic acid in the nonclipped kidneys are both important in the pathophysiology of the maintenance phase of 2K1C Goldblatt hypertension. Therefore, fenofibrate treatment effectively attenuated hypertension, probably via stimulation of 20-HETE formation in the nonclipped kidney. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  4. High Resolution Helium Ion Scanning Microscopy of the Rat Kidney

    PubMed Central

    Rice, William L.; Van Hoek, Alfred N.; Păunescu, Teodor G.; Huynh, Chuong; Goetze, Bernhard; Singh, Bipin; Scipioni, Larry; Stern, Lewis A.; Brown, Dennis

    2013-01-01

    Helium ion scanning microscopy is a novel imaging technology with the potential to provide sub-nanometer resolution images of uncoated biological tissues. So far, however, it has been used mainly in materials science applications. Here, we took advantage of helium ion microscopy to explore the epithelium of the rat kidney with unsurpassed image quality and detail. In addition, we evaluated different tissue preparation methods for their ability to preserve tissue architecture. We found that high contrast, high resolution imaging of the renal tubule surface is possible with a relatively simple processing procedure that consists of transcardial perfusion with aldehyde fixatives, vibratome tissue sectioning, tissue dehydration with graded methanol solutions and careful critical point drying. Coupled with the helium ion system, fine details such as membrane texture and membranous nanoprojections on the glomerular podocytes were visualized, and pores within the filtration slit diaphragm could be seen in much greater detail than in previous scanning EM studies. In the collecting duct, the extensive and striking apical microplicae of the intercalated cells were imaged without the shrunken or distorted appearance that is typical with conventional sample processing and scanning electron microscopy. Membrane depressions visible on principal cells suggest possible endo- or exocytotic events, and central cilia on these cells were imaged with remarkable preservation and clarity. We also demonstrate the use of colloidal gold probes for highlighting specific cell-surface proteins and find that 15 nm gold labels are practical and easily distinguishable, indicating that external labels of various sizes can be used to detect multiple targets in the same tissue. We conclude that this technology represents a technical breakthrough in imaging the topographical ultrastructure of animal tissues. Its use in future studies should allow the study of fine cellular details and provide

  5. High resolution helium ion scanning microscopy of the rat kidney.

    PubMed

    Rice, William L; Van Hoek, Alfred N; Păunescu, Teodor G; Huynh, Chuong; Goetze, Bernhard; Singh, Bipin; Scipioni, Larry; Stern, Lewis A; Brown, Dennis

    2013-01-01

    Helium ion scanning microscopy is a novel imaging technology with the potential to provide sub-nanometer resolution images of uncoated biological tissues. So far, however, it has been used mainly in materials science applications. Here, we took advantage of helium ion microscopy to explore the epithelium of the rat kidney with unsurpassed image quality and detail. In addition, we evaluated different tissue preparation methods for their ability to preserve tissue architecture. We found that high contrast, high resolution imaging of the renal tubule surface is possible with a relatively simple processing procedure that consists of transcardial perfusion with aldehyde fixatives, vibratome tissue sectioning, tissue dehydration with graded methanol solutions and careful critical point drying. Coupled with the helium ion system, fine details such as membrane texture and membranous nanoprojections on the glomerular podocytes were visualized, and pores within the filtration slit diaphragm could be seen in much greater detail than in previous scanning EM studies. In the collecting duct, the extensive and striking apical microplicae of the intercalated cells were imaged without the shrunken or distorted appearance that is typical with conventional sample processing and scanning electron microscopy. Membrane depressions visible on principal cells suggest possible endo- or exocytotic events, and central cilia on these cells were imaged with remarkable preservation and clarity. We also demonstrate the use of colloidal gold probes for highlighting specific cell-surface proteins and find that 15 nm gold labels are practical and easily distinguishable, indicating that external labels of various sizes can be used to detect multiple targets in the same tissue. We conclude that this technology represents a technical breakthrough in imaging the topographical ultrastructure of animal tissues. Its use in future studies should allow the study of fine cellular details and provide

  6. Angiostatin production increases in response to decreased nitric oxide in aging rat kidney.

    PubMed

    Satoh, Minoru; Kidokoro, Kengo; Ozeki, Masahito; Nagasu, Hajime; Nishi, Yuko; Ihoriya, Chieko; Fujimoto, Sohachi; Sasaki, Tamaki; Kashihara, Naoki

    2013-03-01

    The development of interstitial fibrosis occurs with aging. Impaired angiogenesis, associated with progressive loss of the renal microvasculature, is thought to be a cause of age-related nephropathy. However, the mechanism of capillary loss in aging kidney has not been fully elucidated. Angiostatin is a kringle-containing fragment of plasminogen and is a potent inhibitor of angiogenesis in vivo. Whether angiostatin generation is increased in the aging kidney has not been investigated. We examined 4, 10, 16, and 24-month-old Sprague-Dawley rats for angiostatin production and found that angiostatin generation was increased in aged rats. The protein expression and the activity of cathepsin D-the enzyme for angiostatin production--were increased in aged rats. In the aging kidney, nitric oxide (NO) availability is decreased. To investigate the role of NO in angiostatin production, human umbilical vein endothelial cells were treated with L-NG-nitroarginine methyl ester (L-NAME). L-NAME-treated cells showed increased cathepsin D activity and angiostatin production. For in vivo experiments, 16- to 18-month-old rats were treated with L-NAME or molsidomine for 3 months. Angiostatin production was increased in L-NAME-treated kidney, accompanied by increased cathepsin D activity. In contrast, angiostatin production was decreased in molsidomine-treated kidney, accompanied by decreased cathepsin D activity. In conclusion, angiostatin generation by cathepsin D was increased in the aging rat kidney. Decreased NO production activated cathepsin D activity. Increased angiostatin production may be related to capillary loss and interstitial damage in the aging rat kidney.

  7. Tinospora cordifolia consumption ameliorates changes in kidney chondroitin sulphate/dermatan sulphate in diabetic rats

    PubMed Central

    Joladarashi, Darukeshwara; Chilkunda, Nandini D.; Salimath, Paramahans V.

    2012-01-01

    Diabetes is known to alter kidney extracellular matrix (ECM) components. Chondroitin sulphate (CS)/dermatan sulphate (DS), an ECM component, which plays an essential role in kidney is altered during diabetes. The focus of this study has been to examine the effect of Tinospora cordifolia (TC) consumption, a potent plant widely used to treat diabetes, on kidney CS/DS. Experimentally induced diabetic rats were fed with diet containing TC at 2·5 and 5 % levels and the effect of it on kidney CS/DS was examined. The CS/DS content and CS:heparan sulphate ratio which was decreased during diabetic condition were ameliorated in TC-fed groups. Disaccharide composition analysis of CS/DS by HPLC showed that decreases in ‘E’ units and degree of sulphation were modulated in 5 % TC-fed groups. Apparent molecular weight of purified CS/DS from the control rat kidney was found to be 38 kDa which was decreased to 29 kDa in diabetic rat kidney. Rats in 5 % TC-fed groups showed chain length of 38 kDa akin to control rats. Expression of chondroitin 4-O-sulfotransferase-1, dermatan 4-O-sulfotransferase-1 and N-acetylgalactosamine 4 sulphate 6-O-sulfotransferase, enzymes involved in the synthesis of ‘E’ units which was reduced during diabetic condition, was significantly contained in the 5 % TC-fed group. Purified CS/DS from 5 % TC-fed group was able to bind higher amounts of ECM components, namely type IV collagen and laminin, when compared with untreated diabetic rats. The present results demonstrate that consumption of a diet containing TC at the 5 % level modulates changes in kidney CS/DS which were due to diabetes. PMID:25191554

  8. Tinospora cordifolia consumption ameliorates changes in kidney chondroitin sulphate/dermatan sulphate in diabetic rats.

    PubMed

    Joladarashi, Darukeshwara; Chilkunda, Nandini D; Salimath, Paramahans V

    2012-01-01

    Diabetes is known to alter kidney extracellular matrix (ECM) components. Chondroitin sulphate (CS)/dermatan sulphate (DS), an ECM component, which plays an essential role in kidney is altered during diabetes. The focus of this study has been to examine the effect of Tinospora cordifolia (TC) consumption, a potent plant widely used to treat diabetes, on kidney CS/DS. Experimentally induced diabetic rats were fed with diet containing TC at 2·5 and 5 % levels and the effect of it on kidney CS/DS was examined. The CS/DS content and CS:heparan sulphate ratio which was decreased during diabetic condition were ameliorated in TC-fed groups. Disaccharide composition analysis of CS/DS by HPLC showed that decreases in 'E' units and degree of sulphation were modulated in 5 % TC-fed groups. Apparent molecular weight of purified CS/DS from the control rat kidney was found to be 38 kDa which was decreased to 29 kDa in diabetic rat kidney. Rats in 5 % TC-fed groups showed chain length of 38 kDa akin to control rats. Expression of chondroitin 4-O-sulfotransferase-1, dermatan 4-O-sulfotransferase-1 and N-acetylgalactosamine 4 sulphate 6-O-sulfotransferase, enzymes involved in the synthesis of 'E' units which was reduced during diabetic condition, was significantly contained in the 5 % TC-fed group. Purified CS/DS from 5 % TC-fed group was able to bind higher amounts of ECM components, namely type IV collagen and laminin, when compared with untreated diabetic rats. The present results demonstrate that consumption of a diet containing TC at the 5 % level modulates changes in kidney CS/DS which were due to diabetes.

  9. Mephedrone exposure in adolescent rats alters the rewarding effect of morphine in adults.

    PubMed

    Joanna, Listos; Sylwia, Talarek; Magdalena, Gryzinska; Piotr, Listos; Ewa, Kedzierska; Jolanta, Orzelska-Gorka; Malgorzata, Dylewska; Malgorzata, Lupina; Kotlinska, Jolanta H

    2017-09-05

    An increasing number of data show that exposure to mephedrone in adolescence can have long-lasting implication on brain activity and on peripheral organs/tissues. The aim of this study was to investigate whether adolescent exposure to mephedrone (10mg/kg, i.p.) has influence upon the rewarding effect of morphine (5mg/kg, i.p.) in adult rats. Thus, the adolescent rats (on the 30th PND) were treated with mephedrone for 7 consecutive days. When the animals were adult (on the 60th PND) the morphine-induced conditioned place preference (CPP) test was performed. After that, the level of DNA methylation in the striatum was investigated. DNA methylation is one of the epigenetic mechanisms which produces changes in the genome. These alterations may affect the phenotype, without effect on DNA sequences, and has influence on drug addiction. Additionally, in order to check the toxic properties of mephedrone on the peripheral organs, the histopathological examination of kidney and liver was carried out. The present experiments demonstrated that: 1) adolescent mephedrone exposure may intensify the rewarding effect of morphine in adult rats in the CPP test; 2) mephedrone may induce the alterations in DNA methylation in striatum of adult rats leading to changes in gene activity; 3) mephedrone may produce some retrogressive disturbances in kidney and liver, which confirms the toxic properties of this substance. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Age-related changes in the function of autophagy in rat kidneys.

    PubMed

    Cui, Jing; Bai, Xue-Yuan; Shi, Suozhu; Cui, Shaoyuan; Hong, Quan; Cai, Guangyan; Chen, Xiangmei

    2012-04-01

    Autophagy is a highly regulated intracellular process for the degradation of cytoplasmic components, especially protein aggregates and damaged organelles. It is essential for maintaining healthy cells. Impaired or deficient autophagy is believed to cause or contribute to aging and age-related disease. In this study, we investigated the effects of age on autophagy in the kidneys of 3-, 12-, and 24-month-old Fischer 344 rats. The results revealed that autophagy-related gene (Atg)7 was significantly downregulated in kidneys of increasing age. The protein expression level of the autophagy marker light chain 3/Atg8 exhibited a marked decline in aged kidneys. The levels of p62/SQSTM1 and polyubiquitin aggregates, representing the function of autophagy and proteasomal degradation, increased in older kidneys. The level of 8-hydroxydeoxyguanosine, a marker of mitochondrial DNA oxidative damage, was also increased in older kidneys. Analysis by transmission electron microscope demonstrated swelling and disintegration of cristae in the mitochondria of aged kidneys. These results suggest that autophagic function decreases with age in the kidneys of Fischer 344 rats, and autophagy may mediate the process of kidney aging, leading to the accumulation of damaged mitochondria.

  11. Decrease of Klotho in the Kidney of Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Cheng, Meng-Fu; Chen, Li-Jen; Cheng, Juei-Tang

    2010-01-01

    The klotho gene is expressed in a limited number of tissues, most notably in distal convoluted tubules in the kidney and choroid plexus in the brain. A previous study suggested that Klotho increases resistance to oxidative stress. However, changes of Klotho expression in high glucose-induced oxidative stress remain unclear. In the present study, we used streptozotocin-induced diabetic rats (STZ rats) to examine the effects of insulin, phloridzin or antioxidant, tiron on diabetic nephropathy. Both insulin and phloridzin reversed the lower Klotho expression levels in kidneys of STZ rats by the correction of hyperglycemia. Also, renal functions were improved by these treatments. In addition to the improvement of renal functions, the decrease of Klotho expression in kidney of STZ rats was also reversed by tiron without changing blood glucose levels. The reduction of oxidative stress induced by high glucose can be considered for this action of tiron. This view was further confirmed in vitro using high glucose-exposed Madin-Darby canine kidney (MDCK) epithelial cells. Thus, we suggest that decrease of oxidative stress is not only responsible for the improvement of renal function but also for the recovery of Klotho expression in kidney of STZ rats. PMID:20625492

  12. Distribution study of cisplatin in rat kidney and liver cancer tissues by using liquid chromatography electrospray ionization tandem mass spectrometry.

    PubMed

    Bandu, Raju; Ahn, Hyun Soo; Lee, Joon Won; Kim, Yong Woo; Choi, Seon Hee; Kim, Hak Jin; Kim, Kwang Pyo

    2015-06-01

    A sensitive and rapid liquid chromatography positive ion electrospray ionization tandem mass spectrometric (LC/ESI-MS/MS) method has been developed and validated for the quantitative determination and distribution of cisplatin (CP) in kidney and liver tissues after intravenous administration of drug to adult male Sprague Dawley rats. Oxaliplatin (OXP) was used as an internal standard. The tissue samples were homogenized and extracted using conventional liquid-liquid extraction method with phosphate buffer containing ethyl acetate and then subjected to LC-MS analysis. The chromatographic separation was achieved on an Agilent ZORBAX SB C-18 column (50 × 2.1 mm, 1.8 µm) using the mobile phase consisting of 0.1% formic acid in water (Solvent A) : methanol (Solvent B) (40 : 60; v/v) in an isocratic elution followed by detection with positive ion electrospray ionization tandem mass spectrometry using the transitions of m/z 301 > 265 for CP and m/z 398 > 310 for OXP in multiple reaction monitoring mode. The calibration curve was linear in the range of 5.0-7000 and 10.0-6000 ng/ml for kidney and liver tissue homogenates, respectively. The method revealed good performances in terms of within-batch, between-batch precision (1.31-5.70%) and accuracy (97.0-102.24%) for CP in both kidney and liver tissue homogenates including lower and upper limits of quantification. The recoveries from spiked control samples were >81.0% and >87.0 % for CP and OXP, respectively. Matrix effect was found to be negligible, and the stability data were within the acceptable limits. Further, the validated LC/ES-MS/MS method was successfully applied to investigate the distribution of CP in kidney and liver tissues after intravenous administration of CP to male Sprague Dawley rats. The results showed that the higher amount of CP was distributed in kidney followed by liver, which indicated that CP mainly accumulated in kidney tissues and renal excretion might be a primary and

  13. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery

    PubMed Central

    Koyner, Jay L.; Bennett, Michael R.; Worcester, Elaine M.; Ma, Qing; Raman, Jai; Jeevanandam, Valluvan; Kasza, Kristen E.; O' Connor, Michael F.; Konczal, David J.; Trevino, Sharon; Devarajan, Prasad; Murray, Patrick T.

    2009-01-01

    There is a need to develop early biomarkers of acute kidney injury following cardiac surgery, where morbidity and mortality are increased by its presence. Plasma cystatin C (CyC) and plasma and urine Neutrophil Gelatinase Associated Lipocalin (NGAL) have been shown to detect kidney injury earlier than changes in plasma creatinine in critically ill patients. In order to determine the utility of urinary CyC levels as a measure of kidney injury, we prospectively collected plasma and urine from 72 adults undergoing elective cardiac surgery for analysis. Acute kidney injury was defined as a 25% or greater increase in plasma creatinine or renal replacement therapy within the first 72 hours following surgery. Plasma CyC and NGAL were not useful predictors of acute kidney injury within the first 6 hours following surgery. In contrast, both urinary CyC and NGAL were elevated in the 34 patients who later developed acute kidney injury, compared to those with no injury. The urinary NGAL at the time of ICU arrival and the urinary CyC level 6 hours after ICU admission were most useful for predicting acute kidney injury. A composite time point consisting of the maximum urinary CyC achieved in the first 6 hours following surgery outperformed all individual time points. Our study suggests that urinary CyC and NGAL are superior to conventional and novel plasma markers in the early diagnosis of acute kidney injury following adult cardiac surgery. PMID:18650797

  14. Polycystin-1 expression in fetal, adult and autosomal dominant polycystic kidney.

    PubMed

    Chae, Seoung Wan; Cho, Eun-Yoon; Park, Moon Soo; Lee, Kyu-Beck; Kim, Hyunho; Kim, Unkyung

    2006-06-01

    The mutation of the PKD1 gene causes autosomal dominant polycystic kidney disease (ADPKD), and the PKD1 gene encodes polycystin-1 (PC-1). PC-1 is thought to be a cell-cell/matrix adhesion receptor molecule at the cell surface that is widely expressed in the kidney. However, there are controversies about the role of PC-1 protein and its expression when using different antibodies to detect it. We used two PC-1 antibodies; C-20 (Santa Cruz, sc-10372) as the C-terminal antibody, and P-15 (Santa Cruz, sc-10307) as the N-terminal antibody. We evaluated the PC-1 expression by performing immunoblotting on the human embryonic kidney (HEK) 293 cells and the renal proximal tubular epithelial cell (RPTEC) lysates. We characterized the expression of PC-1 in the fetal, adult and polycystic kidneys tissues by performing immunohistochemistry. We confirmed the PC-1 expression in the HEK 293 cells and the RPTEC lysates, but the expression was very low. The PC-1 proteins were diffusely expressed in the tubular epithelial cells cytoplasm in the fetal and adult kidneys, and the PC-1 expression was more prominent in the proximal tubules of the fetal kidney. In the ADPKD kidney, the PC-1 proteins were heterogenously and weakly expressed in the tubular or cyst lining epithelial cells. Our data suggests that the development of the kidney may regulate the expression of PC-1, and an altered PC-1 expression may contribute to cyst formation in ADPKD.

  15. Polycystin-1 Expression in Fetal, Adult and Autosomal Dominant Polycystic Kidney

    PubMed Central

    Chae, Seoung Wan; Cho, Eun-Yoon; Park, Moon Soo; Kim, Hyunho; Kim, Unkyung

    2006-01-01

    The mutation of the PKD1 gene causes autosomal dominant polycystic kidney disease (ADPKD), and the PKD1 gene encodes polycystin-1 (PC-1). PC-1 is thought to be a cell-cell/matrix adhesion receptor molecule at the cell surface that is widely expressed in the kidney. However, there are controversies about the role of PC-1 protein and its expression when using different antibodies to detect it. We used two PC-1 antibodies; C-20 (Santa Cruz, sc-10372) as the C-terminal antibody, and P-15 (Santa Cruz, sc-10307) as the N-terminal antibody. We evaluated the PC-1 expression by performing immunoblotting on the human embryonic kidney (HEK) 293 cells and the renal proximal tubular epithelial cell (RPTEC) lysates. We characterized the expression of PC-1 in the fetal, adult and polycystic kidneys tissues by performing immunohistochemistry. We confirmed the PC-1 expression in the HEK 293 cells and the RPTEC lysates, but the expression was very low. The PC-1 proteins were diffusely expressed in the tubular epithelial cells cytoplasm in the fetal and adult kidneys, and the PC-1 expression was more prominent in the proximal tubules of the fetal kidney. In the ADPKD kidney, the PC-1 proteins were heterogenously and weakly expressed in the tubular or cyst lining epithelial cells. Our data suggests that the development of the kidney may regulate the expression of PC-1, and an altered PC-1 expression may contribute to cyst formation in ADPKD. PMID:16778383

  16. Association Between Kidney Dysfunction and Carotid Atherosclerosis in Community-Based Older Adults in China.

    PubMed

    Gu, Xiang; Fang, Xianghua; Hua, Yang; Tang, Zhe; Ji, Xunming; Guan, Shaochen; Wu, Xiaoguang; Liu, Hongjun; Liu, Beibei; Wang, Chunxiu; Zhang, Zhongying

    2016-03-01

    We investigated the association between kidney dysfunction and carotid atherosclerosis in community-based older adults. This study consisted of 1257 participants, aged 55 years and older and free of cardiovascular disease. Kidney dysfunction was classified as mild, moderate, and severe (estimated glomerular filtration rate, 45-59, 30-44, and <30 mL/min/1.73 m(2), respectively). We found that the mean common carotid artery intima-media thickness (CCA-IMT) progressively increased with decrement in kidney function (P < .001). Even mild kidney dysfunction was significantly associated with CCA-IMT thickening (CCA-IMT ≥1.0 mm; odds ratio [OR] 1.52; 95% confidence interval [CI] 1.16-1.99) compared to normal kidney function. A significantly increased presence of heterogeneous plaque was observed in relation to decreased kidney function (P for trend = .011), that is, even a mild kidney dysfunction was a potential independent risk factor for heterogeneous plaque (OR 1.43; 95% CI 1.04-1.98). Mild kidney dysfunction may be a predictor of early or accelerated carotid atherosclerosis in older adults.

  17. Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats.

    PubMed

    Shao, Weijian; Miyata, Kayoko; Katsurada, Akemi; Satou, Ryousuke; Seth, Dale M; Rosales, Carla B; Prieto, Minolfa C; Mitchell, Kenneth D; Navar, L Gabriel

    2016-08-01

    In angiotensin II (ANG II)-dependent hypertension, there is an angiotensin type 1 receptor-dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion in the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of two-kidney, one-clip Sprague-Dawley hypertensive rats subjected to left renal arterial clipping (0.25-mm gap). By 18-21 days, systolic arterial pressure increased to 180 ± 3 mmHg, and uAGT increased. Water intake, body weights, 24-h urine volumes, and sodium excretion were similar. In separate measurements of renal function in anesthetized rats, renal plasma flow and glomerular filtration rate were similar in clipped and nonclipped kidneys and not different from those in sham rats, indicating that the perfusion pressure to the clipped kidneys remained within the autoregulatory range. The nonclipped kidneys exhibited increased urine flow and sodium excretion. The uAGT excretion was significantly greater in nonclipped kidneys compared with clipped and sham kidneys. AGT mRNA was 2.15-fold greater in the nonclipped kidneys compared with sham (1.0 ± 0.1) or clipped (0.98 ± 0.15) kidneys. AGT protein levels were also greater in the nonclipped kidneys. The nonclipped kidneys exhibited greater glomerular expansion and immune cell infiltration, medullary fibrosis, and cellular proliferation than the clipped kidneys. Because both kidneys have elevated ANG II levels, the greater tissue injury in the nonclipped kidneys indicates that an increased arterial pressure synergizes with increased intrarenal ANG II to stimulate AGT production and exert greater renal injury.

  18. Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease.

    PubMed

    van Koppen, Arianne; Joles, Jaap A; van Balkom, Bas W M; Lim, Sai Kiang; de Kleijn, Dominique; Giles, Rachel H; Verhaar, Marianne C

    2012-01-01

    Chronic kidney disease (CKD) is a major health care problem, affecting more than 35% of the elderly population worldwide. New interventions to slow or prevent disease progression are urgently needed. Beneficial effects of mesenchymal stem cells (MSC) have been described, however it is unclear whether the MSCs themselves or their secretome is required. We hypothesized that MSC-derived conditioned medium (CM) reduces progression of CKD and studied functional and structural effects in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX) combined with L-NNA and 6% NaCl diet in Lewis rats. Six weeks after SNX, CKD rats received either 50 µg CM or 50 µg non-CM (NCM) twice daily intravenously for four consecutive days. Six weeks after treatment CM administration was functionally effective: glomerular filtration rate (inulin clearance) and effective renal plasma flow (PAH clearance) were significantly higher in CM vs. NCM-treatment. Systolic blood pressure was lower in CM compared to NCM. Proteinuria tended to be lower after CM. Tubular and glomerular damage were reduced and more glomerular endothelial cells were found after CM. DNA damage repair was increased after CM. MSC-CM derived exosomes, tested in the same experimental setting, showed no protective effect on the kidney. In a rat model of established CKD, we demonstrated that administration of MSC-CM has a long-lasting therapeutic rescue function shown by decreased progression of CKD and reduced hypertension and glomerular injury.

  19. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults.

    PubMed

    Kaddourah, Ahmad; Basu, Rajit K; Bagshaw, Sean M; Goldstein, Stuart L

    2017-01-05

    The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury. We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality. A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output. Acute kidney injury is common and is associated with poor outcomes, including increased mortality, among critically ill children

  20. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults

    PubMed Central

    Kaddourah, Ahmad; Basu, Rajit K.; Bagshaw, Sean M.; Goldstein, Stuart L.

    2017-01-01

    Background The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury. Methods We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality. Results A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output. Conclusions Acute kidney injury is common and is associated with poor outcomes, including increased

  1. Role of aldosterone in the remnant kidney model in the rat.

    PubMed Central

    Greene, E L; Kren, S; Hostetter, T H

    1996-01-01

    The renin-angiotensin-aldosterone system (RAAS) participates in the injury sustained by the remnant kidney. Our studies assessed the importance of aldosterone in that model and the response of aldosterone to drugs interfering with the RAAS. Initially, four groups of rats were studied: SHAM-operated rats, untreated remnant rats (REM), REM rats treated with losartan and enalapril (REM AIIA), and REM AIIA rats infused with exogenous aldosterone (REM AIIA + ALDO). The last group was maintained with aldosterone levels comparable to those in untreated REM rats by constant infusion of exogenous aldosterone. REM rats had larger adrenal glands and a > 10-fold elevation in plasma aldosterone compared to SHAM. REM AIIA rats demonstrated significant suppression of the hyperaldosteronism as well as marked attenuation of proteinuria, hypertension, and glomerulosclerosis compared to REM. REM AIIA + ALDO rats manifested greater proteinuria, hypertension, and glomerulosclerosis than REM AIIA rats. Indeed, by 4 wk of observation all of these features of the experimental disease were similar in magnitude in REM AIIA + ALDO and untreated REM. In separate REM rats spironolactone administration did not reduce glomerular sclerosis but did transiently reduce proteinuria, lowered arterial pressure, and lessened cardiac hypertrophy. In summary, aldosterone contributes to hypertension and renal injury in the remnant kidney model. PMID:8770880

  2. Comparative toxicity to weanling and adult rats of lead acetate in water

    SciTech Connect

    Rader, J.I.; Celesk, E.M.; Peeler, J.T.; Mahaffey, K.R.

    1981-06-01

    The relative toxicity of lead acetate provided at uniform exposure levels (..mu..g/ml in water) or at uniform dosages (mg/kg body wt) was studied in groups of weanling and adult rats. Free erythrocyte protoporphyrins, urinary delta-aminolevulinic acid and blood Pb levels were measured. The accumulation of Pb in brain, kidney and bone (femur) was measured to determine the effect of age on tissue distribution and retention of Pb. Under conditions in which both weanling and adult rats were exposed to the same concentrations of Pb in drinking water, toxic effects of the metal were more pronounced in weanlings than in adults. This was due in part to higher doses of Pb per kg of body weight ingested by the young animals under these conditions. Under conditions of uniform dosage, retention of Pb (as % of ingested dose) in brain tissue and femur was significantly higher in weanling than adult animals.

  3. Fate of injected interleukin 1 in rats: Sequestration and degradation in the kidney

    SciTech Connect

    Poole, S.; Bird, T.A.; Selkirk, S.; Gaines-Das, R.E.; Choudry, Y.; Stephenson, S.L.; Kenny, A.J.; Saklatvaa, J. )

    1990-11-01

    The tissue distribution and route of clearance of human recombinant interleukin 1 alpha (IL 1 alpha) injected intravenously in rats was studied. The plasma half-life was approximately 2.5 min, and this was increased after nephrectomy, the kidney being the major organ through which the IL 1 alpha was excreted. Two iodinated fragments of IL 1 alpha, of approximately 5 and 9 kDa, were excreted by the kidneys whereas only intact, 17-kDa IL 1 alpha was detected in plasma, suggesting that the protein was being degraded after uptake by the kidney. The results of in vivo experiments in which surface endopeptidase-24.11 was inhibited with phosphoramidon and in vitro experiments in which rat kidney homogenates were incubated with radiolabeled IL 1 alpha suggest that the cytokine was endocytosed and then hydrolysed by lysosomal proteinases.

  4. Human hepatocyte and kidney cell metabolism of 2-acetylaminofluorene and comparison to the respective rat cells.

    PubMed

    Langenbach, R; Rudo, K

    1988-12-01

    The metabolism and mutagenic activation of 2-acetylaminofluorene by human and rat hepatocytes and kidney cells were measured. High performance liquid chromatography was used to separate the 2-acetylaminofluorene metabolites, and a cell-mediated Salmonella typhimurium mutagenesis assay was used to detect mutagenic intermediates. Rat and human differences were observed with cells from both organs and levels of metabolism and mutagenesis were higher in human cells. Within a species, liver and kidney cell differences were also evident, with levels of hepatocyte-mediated metabolism and mutagenesis being greater than kidney cells. Human inter-individual variation was apparent with cells from both organs, but the variation observed was significantly greater in hepatocytes than kidney cells. A knowledge of such differences, including an understanding that they may vary with the chemical being studied, should be useful in the extrapolation of rodent carcinogenesis data to humans.

  5. Structural transition of kidney cystatin in dimethylnitrosamine-induced renal cancer in rats: identification as a novel biomarker for kidney cancer and prognosis.

    PubMed

    Shamsi, Anas; Ahmed, Azaj; Bano, Bilqees

    2017-04-01

    In our study, renal cancer is induced in rats making use of dimethylnitrosamine (DMN). G1 - Group 1 were control rats and G2 - Group 2 rats were given a single intra-peritoneal injection of DMN of 50 mg/kg body weight resulting in 100% incidences of renal tumors after 12 months. SEM and histopathology confirmed the presence of renal cancer in the DMN-treated rats. Making use of ammonium sulfate precipitation and gel filtration chromatography on Sephacryl S-100HR column, a thiol protease inhibitor was isolated from kidney of control rats known as Rat kidney Cystatin (RKC) as well as from kidney of cancerous rat called as Cancerous Rat Kidney Cystatin (CRKC). Both these inhibitors were characterized, and interestingly, it was found that CRKC showed greater anti-papain activity and also it was stable in a broad pH and temperature range thus implying that CRKC is more stable as compared to RKC. UV and fluorescence spectroscopy point out in structural difference between RKC and CRKC which was further confirmed by Circular dichroism (CD) and FTIR spectroscopy. Our study clearly showed that kidney cystatin is structurally modified in the case of renal cancer and performs its role in a more efficacious manner.

  6. Analysis of nephron composition and function in the adult zebrafish kidney.

    PubMed

    McCampbell, Kristen K; Springer, Kristin N; Wingert, Rebecca A

    2014-08-09

    The zebrafish model has emerged as a relevant system to study kidney development, regeneration and disease. Both the embryonic and adult zebrafish kidneys are composed of functional units known as nephrons, which are highly conserved with other vertebrates, including mammals. Research in zebrafish has recently demonstrated that two distinctive phenomena transpire after adult nephrons incur damage: first, there is robust regeneration within existing nephrons that replaces the destroyed tubule epithelial cells; second, entirely new nephrons are produced from renal progenitors in a process known as neonephrogenesis. In contrast, humans and other mammals seem to have only a limited ability for nephron epithelial regeneration. To date, the mechanisms responsible for these kidney regeneration phenomena remain poorly understood. Since adult zebrafish kidneys undergo both nephron epithelial regeneration and neonephrogenesis, they provide an outstanding experimental paradigm to study these events. Further, there is a wide range of genetic and pharmacological tools available in the zebrafish model that can be used to delineate the cellular and molecular mechanisms that regulate renal regeneration. One essential aspect of such research is the evaluation of nephron structure and function. This protocol describes a set of labeling techniques that can be used to gauge renal composition and test nephron functionality in the adult zebrafish kidney. Thus, these methods are widely applicable to the future phenotypic characterization of adult zebrafish kidney injury paradigms, which include but are not limited to, nephrotoxicant exposure regimes or genetic methods of targeted cell death such as the nitroreductase mediated cell ablation technique. Further, these methods could be used to study genetic perturbations in adult kidney formation and could also be applied to assess renal status during chronic disease modeling.

  7. Analysis of Nephron Composition and Function in the Adult Zebrafish Kidney

    PubMed Central

    McCampbell, Kristen K.; Springer, Kristin N.; Wingert, Rebecca A.

    2014-01-01

    The zebrafish model has emerged as a relevant system to study kidney development, regeneration and disease. Both the embryonic and adult zebrafish kidneys are composed of functional units known as nephrons, which are highly conserved with other vertebrates, including mammals. Research in zebrafish has recently demonstrated that two distinctive phenomena transpire after adult nephrons incur damage: first, there is robust regeneration within existing nephrons that replaces the destroyed tubule epithelial cells; second, entirely new nephrons are produced from renal progenitors in a process known as neonephrogenesis. In contrast, humans and other mammals seem to have only a limited ability for nephron epithelial regeneration. To date, the mechanisms responsible for these kidney regeneration phenomena remain poorly understood. Since adult zebrafish kidneys undergo both nephron epithelial regeneration and neonephrogenesis, they provide an outstanding experimental paradigm to study these events. Further, there is a wide range of genetic and pharmacological tools available in the zebrafish model that can be used to delineate the cellular and molecular mechanisms that regulate renal regeneration. One essential aspect of such research is the evaluation of nephron structure and function. This protocol describes a set of labeling techniques that can be used to gauge renal composition and test nephron functionality in the adult zebrafish kidney. Thus, these methods are widely applicable to the future phenotypic characterization of adult zebrafish kidney injury paradigms, which include but are not limited to, nephrotoxicant exposure regimes or genetic methods of targeted cell death such as the nitroreductase mediated cell ablation technique. Further, these methods could be used to study genetic perturbations in adult kidney formation and could also be applied to assess renal status during chronic disease modeling. PMID:25145398

  8. Magnetic resonance imaging (MRI) and pathophysiology of the rat kidney in streptozotocin-induced diabetes

    SciTech Connect

    Lohr, J.; Mazurchuk, R.J.; Acara, M.A.; Nickerson, P.A.; Fiel, R.J. )

    1991-01-01

    Proton magnetic resonance imaging was performed on rats before induction of diabetes with streptozotocin (STZ) and at 2 and 12 days postinduction. Images revealed an increase in maximal longitudinal and axial dimensions of the kidneys at 2 days and a further increase at 12 days. Similarly, an increase in the size of the remaining kidney was seen in a rat which underwent uninephrectomy as a positive control. Two major differences were observed between the kidney undergoing compensatory hypertrophy and those developing diabetic nephropathy: (i) Expansion of the renal vasculature was seen only in images of the diabetic rat; (ii) A loss in conspicuity of the normal corticomedullary junction was seen in the T2-weighted images of the diabetic rat but not in the uninephrectomized rat. Histologic examination revealed that the medulla increased to a size greater than the cortex during diabetic nephropathy whereas the medullary volume was less than that of the cortex during compensatory hypertrophy. In vitro T1 relaxation times in cortex, outer medulla and inner medulla of kidneys from control rats were measured and compared with the same respective regions in diabetic rats. When these values were correlated with tissue water content, a linear increase in relaxation rate versus percent water content from cortex to inner medulla was found in the control kidneys, but this correlation was absent in diabetic nephropathy. These studies demonstrate that MRI is an effective noninvasive tool for studying the course of renal hypertrophy and hydration changes in the development of renal disease in STZ-induced diabetes in the rat.

  9. Metabolism of glycine- and hydroxyproline-containing peptides by the isolated perfused rat kidney.

    PubMed

    Lowry, M; Hall, D E; Brosnan, J T

    1985-07-15

    Isolated perfused rat kidneys removed considerable quantities of glycyltyrosine, glycylhydroxyproline, tetraglycine and prolylhydroxyproline from the perfusate. The component amino acids are released into the perfusate and, in the case of the glycine-containing peptides, there is increased synthesis of serine. Removal of peptides was more than could be accounted for on the basis of filtration, so antiluminal metabolism is indicated. Metabolism of such peptides by the kidney may contribute to renal serine synthesis in vivo.

  10. Metabolism of glycine- and hydroxyproline-containing peptides by the isolated perfused rat kidney.

    PubMed Central

    Lowry, M; Hall, D E; Brosnan, J T

    1985-01-01

    Isolated perfused rat kidneys removed considerable quantities of glycyltyrosine, glycylhydroxyproline, tetraglycine and prolylhydroxyproline from the perfusate. The component amino acids are released into the perfusate and, in the case of the glycine-containing peptides, there is increased synthesis of serine. Removal of peptides was more than could be accounted for on the basis of filtration, so antiluminal metabolism is indicated. Metabolism of such peptides by the kidney may contribute to renal serine synthesis in vivo. PMID:4038280

  11. Chronic trimethyltin chloride exposure and the development of kidney stones in rats.

    PubMed

    Ren, Xuefeng; Wu, Xin; Sui, Gang; Gong, Zhihong; Yawson, Emmanuel; Wu, Banghua; Lai, Guanchao; Ruan, Xiaolin; Gao, Hongbin; Zhou, Feng; Su, Bing; Olson, James R; Tang, Xiaojiang

    2015-05-01

    We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague-Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg(-1) day(-1). Transient behavioral changes were observed in the high-dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H(+)/K(+)-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg(-1) day(-1) dose group and 3 out of 9 rats in the 131.3 µg kg(-1) day(-1) dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones.

  12. Chronic trimethyltin chloride exposure and the development of kidney stones in rats

    PubMed Central

    Ren, Xuefeng; Wu, Xin; Sui, Gang; Gong, Zhihong; Yawson, Emmanuel; Wu, Banghua; Lai, Guanchao; Ruan, Xiaolin; Gao, Hongbin; Zhou, Feng; Su, Bing; Olson, James R.; Tang, Xiaojiang

    2015-01-01

    We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague–Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 μg kg−1 day−1. Transient behavioral changes were observed in the high-dose group during the first 2weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H+/K+-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 μg kg−1 day−1 dose group and 3 out of 9 rats in the 131.3 μg kg−1 day−1 dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones. PMID:25224689

  13. Influence of vanadium-organic ligands treatment on selected metal levels in kidneys of STZ rats.

    PubMed

    Krośniak, Mirosław; Kowalska, Joanna; Francik, Renata; Gryboś, Ryszard; Blusz, Magdalena; Kwiatek, Wojciech M

    2013-06-01

    The objective of the study was to investigate the effects of five organic vanadium complexes supplement and a small dose of insulin injection on V, Fe, Cu, Zn, Mn, Ca, and K level in the streptozotocin diabetic rat's kidney during a 5-week treatment with the tested complexes. In all groups of animals, metal level in the lyophilized kidney organs was investigated by means of the proton induced X-ray emission method. Tissue vanadium level was naturally higher in vanadium-treated rats. The maximum level of vanadium was observed in the kidney (x(mean) = 16.6 μg/g). The influence of vanadium administration on other metal level in rat's tissue was also investigated. Spectacular influence of vanadium action was observed on copper and zinc level in examined tissue.

  14. Acute graft-versus-host disease of the kidney in allogeneic rat bone marrow transplantation.

    PubMed

    Higo, Seiichiro; Shimizu, Akira; Masuda, Yukinari; Nagasaka, Shinya; Kajimoto, Yusuke; Kanzaki, Go; Fukui, Megumi; Nagahama, Kiyotaka; Mii, Akiko; Kaneko, Tomohiro; Tsuruoka, Shuichi

    2014-01-01

    Allogeneic hematopoietic cell or bone marrow transplantation (BMT) causes graft-versus-host-disease (GVHD). However, the involvement of the kidney in acute GVHD is not well-understood. Acute GVHD was induced in Lewis rats (RT1l) by transplantation of Dark Agouti (DA) rat (RT1(a)) bone marrow cells (6.0 × 10(7) cells) without immunosuppression after lethal irradiation (10 Gy). We examined the impact of acute GVHD on the kidney in allogeneic BMT rats and compared them with those in Lewis-to-Lewis syngeneic BMT control and non-BMT control rats. In syngeneic BMT and non-BMT control rats, acute GVHD did not develop by day 28. In allogeneic BMT rats, severe acute GVHD developed at 21-28 days after BMT in the skin, intestine, and liver with decreased body weight (>20%), skin rush, diarrhea, and liver dysfunction. In the kidney, infiltration of donor-type leukocytes was by day 28. Mild inflammation characterized by infiltration of CD3(+) T-cells, including CD8(+) T-cells and CD4(+) T-cells, and CD68(+) macrophages to the interstitium around the small arteries was noted. During moderate to severe inflammation, these infiltrating cells expanded into the peritubular interstitium with peritubular capillaritis, tubulitis, acute glomerulitis, and endarteritis. Renal dysfunction also developed, and the serum blood urea nitrogen (33.9 ± 4.7 mg/dL) and urinary N-acetyl-β-D-glucosaminidase (NAG: 31.5 ± 15.5 U/L) levels increased. No immunoglobulin and complement deposition was detected in the kidney. In conclusion, the kidney was a primary target organ of acute GVHD after BMT. Acute GVHD of the kidney was characterized by increased levels of urinary NAG and cell-mediated injury to the renal microvasculature and renal tubules.

  15. Elimination of etimicin in rat kidneys and alterations of its cytotoxicity to tubular epithelial cells.

    PubMed

    Li, Z-D; Zhang, X-L; Yi, N; Zhang, F-C

    2015-05-01

    Etimicin (ETM) can accumulate in kidneys and cause tubular epithelial cell cytotoxicity. This article aims to study ETM elimination in kidneys and its nephrotoxicity, apoptosis, and histopathological insults of renal tubular epithelial cells, after repeated administration. A total of 36 rats were randomly divided into ETM-treated group and vehicle control group. Rats in ETM-treated group were treated intraperitoneally (i.p.) with 100 mg/kg/day ETM and rats in control group received physiological saline (i.p.) for 5 consecutive days. Determination of ETM concentrations accumulated in rat kidneys was carried out by high-performance liquid chromatography on the basis of derivatization with o-phthalaldehyde and by ultraviolet detector. Apoptotic renal tubular epithelial cells were identified by a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Histopathological insults in kidneys were evaluated by hematoxylin and eosin staining. On day 1 after cessation of ETM administration, the accumulation concentration was 347.50 ± 193.30 μg/g tissue; on day 15, ETM concentration became 16.71 ± 9.99 μg/g tissue. Elimination half-life of ETM in rat kidney was about 3.05 days. Apoptotic renal tubular epithelial cells induced by etimicin was recovered gradually from 1544 ± 138 n/mm(2) on day 1 to 716 ± 208 n/mm(2) on day 15. Histopathological damage was also gradually recovered from vacuolation of tubular epithelial cells as well as renal tubular edema on days 1, 3, and 7 to nearly normal on day 15. From these results, we concluded that renal tubular epithelial cell cytotoxicity induced by ETM can gradually restore with its decreasing concentration in rat kidneys.

  16. Effects of Zinc Supplementation on DNA Damage in Rats with Experimental Kidney Deficiency.

    PubMed

    Yegin, Sevim Çiftçi; Dede, Semiha; Mis, Leyla; Yur, Fatmagül

    2017-04-01

    This study was carried out to determine the effect of zinc on oxidative DNA damage in rats with experimental acute and chronic kidney deficiency. Six groups of five Wistar-Albino rats each were assigned as controls (C), acute kidney deficiency (AKD), zinc-supplemented (+Zn), acute kidney deficiency, zinc-supplemented (AKD + Zn), chronic kidney deficiency (CKD) and zinc-supplemented chronic kidney deficiency (CKD + Zn). The levels of 8-Oxo-2'-deoxyguanosine (8-OHdG) were determined, being the lowest in the CKD group (p < 0.05), higher in the C group than those of rats with CKD but lower than that of all the other groups (p < 0.05). There were no significant differences between the controls and the CKD + Zn group, or between the AKD and the +Zn groups. Among all groups, the highest 8-OHdG level was found in the AKD + Zn group (p < 0.05). DNA damage was greater in acute renal failure than in rats with chronic renal failure. The DNA damage in the zinc group was significantly higher than in the controls.

  17. Extremely low-frequency magnetic field induces manganese accumulation in brain, kidney and liver of rats.

    PubMed

    Çelik, Mustafa Salih; Güven, Kemal; Akpolat, Veysi; Akdağ, Mehmet Zulkuf; Nazıroğlu, Mustafa; Gül-Güven, Reyhan; Çelik, M Yusuf; Erdoğan, Sait

    2015-06-01

    The aim of the present study was to determine the effects of extremely low-frequency magnetic field (ELF-MF) on accumulation of manganese (Mn) in the kidney, liver and brain of rats. A total of 40 rats were randomly divided into eight groups. Four control groups received 0, 3.75, 15 and 60 mg Mn per kg body weight orally every 2 days for 45 days, respectively. The remaining four groups received same concentrations of Mn and were also exposed to ELF-MF (1.5 mT; 50 Hz) for 4 h for 5 days a week during 45 days. Following the last exposure, kidney, liver and brain were taken from all rats and they were analyzed for Mn accumulation levels using an inductively coupled plasma-optical emission spectrometer. In result of the current study, we observed that Mn levels in brain, kidney and liver were higher in Mn groups than in control groups. Mn levels in brain, kidney and liver were also higher in Mn plus ELF-MF groups than in Mn groups. In conclusion, result of the current study showed that the ELF-MF induced manganese accumulation in kidney, liver and brain of rats.

  18. Characterization of kidney sulfotransferases during lead-induced nephrotoxicity in rats

    SciTech Connect

    Templer, L.A.; Kong, J.; Ronis, M.J.J.; Ringer, D.P.

    1996-03-08

    Kidney sulfotransferases (ST) have been shown to be involved in the biotransformation of steroid and thyroid hormones as well as xenobiotics varying from carcinogenic heterocyclic amines to drugs such as acetaminophen. In order to examine the impact of lead-induced nephrotoxicity on kidney aryl, estrogen and DHEA STs during growth and development, time-impregnated female Sprague-Dawley rats were exposed ad libitum to lead acetate (0.6%) in drinking water from gestational day 5 and continuing in male and female pups until they were sacrificed at day 85. Cytosols from male rat kidneys showed levels of estrogen ST activity (59% of females) that were significantly lowered (P{le}0.05) after lead exposure (6-20% of male). Aryl ST activity was relatively unchanged in male rats after rat kidney cytosol. Immunochemical analysis of cytosols from normal males and females with the antiserums to the three STs substantiated the presence of only the aryl and estrogen STs. Immunohistochemical techniques localized the aryl and estrogen STs primarily to the S3 section of the proximal tubules. These findings indicate that kidney STs may be differently modulated during lead exposure.

  19. Resveratrol improves mitochondrial function in the remnant kidney from 5/6 nephrectomized rats.

    PubMed

    Hui, Yan; Lu, Miaomiao; Han, Yarong; Zhou, Hongli; Liu, Wei; Li, Lijing; Jin, Ruixia

    2017-05-01

    Mitochondrial dysfunction is involved in the pathogenesis of chronic kidney disease (CKD). Resveratrol has been demonstrated to be beneficial for the recovery of kidney diseases. In this study, the 5/6 nephrectomized rat was used as a CKD model and the TGF-β1-exposed mouse mesangial cells were used as an in vitro model. Pathological examination showed that resveratrol treatment attenuated glomerular injury in the remnant kidney of 5/6 nephrectomized rat. Additionally, resveratrol improved mitochondrial function in vivo and in vitro, as evidenced by increasing mitochondrial membrane potential, increasing ATP, decreasing reactive oxygen species production and enhancing activities of complex I and III. Furthermore, the dysregulated expressions of electron transport chain proteins and fission/fusion proteins in the kidney of 5/6 nephrectomize rats and TGF-β1-exposed mesangial cells were restored by resveratrol. Finally, upregulated sirt1 and PGC-1α deacetylation were found after treatment with resveratrol in vivo and in vitro, which may contribute to the mitochondrial protective effects of resveratrol. The results demonstrate that resveratrol protects the mitochondria of kidney in 5/6 nephrectomized rats and TGF-β1 induced mesangial cells. The study provides new insights into the renoprotective mechanisms of resveratrol. Copyright © 2017 Elsevier GmbH. All rights reserved.

  20. Combined effects of fluoride and cadmium on liver and kidney function in male rats.

    PubMed

    Zhang, Junmin; Song, Jingjuan; Zhang, Jun; Chen, Xiao; Zhou, Meixia; Cheng, Guang; Xie, Xinyou

    2013-12-01

    It has been shown that cadmium and fluoride may both have adverse effects on liver and kidney functions, but most studies focus on a single agent. In this study, we observed the effects of cadmium and fluoride on liver and kidney functions using a rat model. Total of 24 Sprague-Dawley male rats were divided into four groups, one control group and three exposure groups that were given cadmium (50 mg/L) and fluoride (100 mg/L) alone or in combination via drinking water. At the 12th week, urine, blood, and kidney tissues were collected. Aspartate transaminase, alanine transaminase (ALT), urinary β2-microglobulin, and albumin were determined. Contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in liver and kidney homogenates were measured to evaluate oxidative stress. There was a significant increase in serum ALT and urinary β2-microglobulin of rats in exposure groups compared with control. Serum ALT and urinary β2-microglobulin of rats exposed to cadmium and fluoride in combination was significantly higher than those treated with cadmium alone and fluoride alone. SOD declined significantly and MDA increased in combination group compared with control and those treated with cadmium and fluoride alone. Cadmium and fluoride co-exposure increase the liver and kidney damage compared with that exposed to cadmium or fluoride alone.

  1. Does remifentanil attenuate renal ischemia–reperfusion injury better than dexmedetomidine in rat kidney?

    PubMed Central

    Erkılıç, E; Kesimci, E; Alaybeyoğlu, F; Kılınç, I; Tural, R; Yazgan, A; Gümüş, T; Sepici Dinçel, A; Dumlu, EG; Kanbak, O

    2017-01-01

    Background Ischemia–reperfusion (I/R) injury is a common cause of patient morbidity and mortality in the perioperative period. Patients undergoing long-lasting, abdominal, and urogenital surgeries with risk factors such as advanced age, peripheral artery disease, diabetes mellitus, renovascular disease, and congestive heart failure are candidates for acute kidney injury (AKI) due to impaired renal perfusion and decreased functional renal reserve. Pharmacological agents with multiple functions and anti-oxidative and anti-inflammation properties may be promising preventative strategies for AKI. Recently, dexmedetomidine (dex) has been postulated to have renoprotective effects. Objectives We aimed to investigate the protective effects of an intravenous anesthetic remifentanil in renal I/R injury in the rat in comparison with dex. Materials and methods A total of 30 Sprague Dawley adult rats were randomly assigned into five groups: the control group (group C, n=6), the sham group (group Sh, n=6, saline-infused rats without I/R injury), the saline group (group S, n=6, saline-infused rats with I/R injury), the remifentanil-treated group (group REM, n=6), and the dexmedetomidine-treated group (group DEX, n=6). The infusions (saline, remifentanil, and dex) were started after anesthesia induction and right nephrectomy and continued until the end of the surgical procedure. In I/R injury groups, the left renal artery and vein were occluded together by a clamp for 30 minutes and reperfusion lasted for 30 minutes. The rats were sacrificed after reperfusion, and the left kidney tissue was harvested. Blood samples were drawn from all animals to evaluate plasma neutrophil gelatinase-associated lipocalin (NGAL) at the beginning, 15 minutes after ischemia, 15 minutes after reperfusion, and 6 hours after the surgical procedure (T0, T1, T2, and T3, respectively). Results The plasma NGAL levels exhibited increase at T1, T2, and T3 compared to the levels at T0 in group S (P<0.05). In

  2. Physical Activity and Kidney Injury in Pediatric and Young Adult Kidney Transplant Recipients.

    PubMed

    Wolf, Mattie F; George, Roshan P; Warshaw, Barry; Wang, Elizabeth; Greenbaum, Larry A

    2016-12-01

    To quantify physical activity and grip strength in pediatric kidney transplant recipients and describe attitudes about exercise and exercise counseling given concerns about allograft injury. This was a cross-sectional analysis of 101 kidney transplant recipients (7-21 years old) >6 months post-transplant. Patients completed the Physical Activity Questionnaire (PAQ). Grip strength was measured with a dynamometer. We asked about activity limitations and provider counseling. Univariate analysis and multiple linear regression were used to determine independent predictors of PAQ score and grip strength z score. We enrolled 101 of 122 eligible patients. Median PAQ score was 2.2 (range 0-5) and was lower compared with controls (P < .001). The average grip strength z score was -1.1 and -0.7 in the right and left hand, respectively. Predictors of lower grip strength were younger age (P = .036), non-African American race (P = .029), lower height z score (P = .010), and longer percentage of lifetime with kidney disease (P = .029). Although 49% and 67% limited exercise before and after transplant, respectively, 67% reported increased activity after transplant. By parent report, provider counseling included limiting certain activities (71%) and encouraging regular exercise (45%). Physical activity and grip strength are low after kidney transplant. Patients perceive an emphasis on exercise limitations rather than the benefits of regular exercise. Interventions that encourage physical activity may be beneficial. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Immunolocalization of Ksp-cadherin in the adult and developing rabbit kidney.

    PubMed

    Thomson, R B; Aronson, P S

    1999-07-01

    The potential for Ksp-cadherin involvement in either the development or maintenance of the metanephric kidney was assessed by immunocytochemical localization of a monoclonal antibody directed against the rabbit isoform of Ksp-cadherin in both neonatal and adult rabbit kidneys. In the adult kidney Ksp-cadherin expression was detected on the basolateral membrane of all cell types in both the tubular nephron and the collecting system. Immunoelectron microscopy indicated that Ksp-cadherin was expressed at uniform levels along the entire length of both the lateral membranes and the basal infoldings of all tubular epithelial cell types. In the nephrogenic zone of the neonatal rabbit kidney Ksp-cadherin expression was detected exclusively on the basolateral membranes of epithelial cells in the more highly differentiated regions of the expanding ureteric duct. In the highly differentiated corticomedullary and medullary regions of the neonatal kidney, distinct basolateral staining was observed in all segments of the tubular nephron and the collecting system. The relatively late appearance of Ksp-cadherin expression in the developing metanephros indicates that Ksp-cadherin probably does not participate in the direction of renal morphogenesis. However, the high levels of Ksp-cadherin expression observed in all segments of the tubular nephron and the collecting system in the adult kidney suggests that it may play a role in the maintenance of the terminally differentiated tubular epithelial phenotype.

  4. Proteomic analysis of kidneys from selenoprotein M transgenic rats in response to increased bioability of selenium

    PubMed Central

    2013-01-01

    Background To characterize changes in global protein expression in kidneys of transgenic rats overexpressing human selenoprotein M (SelM) in response to increased bioabivility of selenium (Sel), total proteins extracted from kidneys of 10-week-old CMV/hSelM Tg and wild-type rats were separated by 2-dimensional gel electrophoresis and measured for changes in expression. Results Ten and three proteins showing high antioxidant enzymatic activity were up- and down-regulated, respectively, in SelM-overexpressing CMV/hSelM Tg rats compared to controls based on an arbitrary 2-fold difference. Up-regulated proteins included LAP3, BAIAP2L1, CRP2, CD73 antigen, PDGF D, KIAA143 homolog, PRPPS-AP2, ZFP313, HSP-60, and N-WASP, whereas down-regulated proteins included ALKDH3, rMCP-3, and STC-1. After Sel treatment, five of the up-regulated proteins were significantly increased in expression in wild-type rats, whereas there were no changes in CMV/hSelM Tg rats. Only two of the down-regulated proteins showed reduced expression in wild-type and Tg rats after Sel treatment. Conclusions These results show the primary novel biological evidences that new functional protein groups and individual proteins in kidneys of Tg rats relate to Sel biology including the response to Sel treatment and SelM expression. PMID:23937859

  5. Proteomic analysis of kidneys from selenoprotein M transgenic rats in response to increased bioability of selenium.

    PubMed

    Goo, Jun Seo; Kim, Yo Na; Choi, Kyung Mi; Hwang, In Sik; Kim, Ji Eun; Lee, Young Ju; Kwak, Moon Hwa; Shim, Sun Bo; Jee, Seung Wan; Lim, Chul Joo; Seong, Je Kyung; Hwang, Dae Youn

    2013-08-12

    To characterize changes in global protein expression in kidneys of transgenic rats overexpressing human selenoprotein M (SelM) in response to increased bioabivility of selenium (Sel), total proteins extracted from kidneys of 10-week-old CMV/hSelM Tg and wild-type rats were separated by 2-dimensional gel electrophoresis and measured for changes in expression. Ten and three proteins showing high antioxidant enzymatic activity were up- and down-regulated, respectively, in SelM-overexpressing CMV/hSelM Tg rats compared to controls based on an arbitrary 2-fold difference. Up-regulated proteins included LAP3, BAIAP2L1, CRP2, CD73 antigen, PDGF D, KIAA143 homolog, PRPPS-AP2, ZFP313, HSP-60, and N-WASP, whereas down-regulated proteins included ALKDH3, rMCP-3, and STC-1. After Sel treatment, five of the up-regulated proteins were significantly increased in expression in wild-type rats, whereas there were no changes in CMV/hSelM Tg rats. Only two of the down-regulated proteins showed reduced expression in wild-type and Tg rats after Sel treatment. These results show the primary novel biological evidences that new functional protein groups and individual proteins in kidneys of Tg rats relate to Sel biology including the response to Sel treatment and SelM expression.

  6. Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication

    PubMed Central

    Xu, Jia-jun; Zhen, Jian-tao; Tang, Li; Lin, Qing-ming

    2017-01-01

    BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury (AKI) in rats with paraquat intoxication. METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group (n=8), paraquat group (n=8) and Xuebijing-treated group (n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing (8 mL/kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-inflammatory cytokines mRNA levels in kidney were assayed using real-time RT-PCR. RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group (P<0.05, respectively). Moreover, interleukin (IL)-1β, IL-6 and TNF-α mRNA levels were significantly higher in the paraquat group (P<0.01, respectively). However, intravenous Xuebijing significantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α mRNA levels, compared with the paraquat group (P<0.05, respectively). CONCLUSION: Intravenous Xuebijing attenuates AKI following paraquat poisoning by suppressing inflammatory response. PMID:28123623

  7. Histological changes in the kidneys of experimental diabetic rats fed with Momordica charantia (bitter gourd) extract.

    PubMed

    Teoh, S L; Abd Latiff, Azian; Das, S

    2010-01-01

    Momordica charantia (MC) or bitter gourd is widely known for its antidiabetic properties. The aim of the present study was to observe the protective effect of MC extract on the kidneys of streptozotocin-induced diabetic rats. Eighteen male Sprague-Dawley rats (n=18) weighing 200+/-50 g were taken for the study. The study comprised of three groups i.e. a non-diabetic, diabetic untreated and diabetic treated with MC extract, with each group comprising of six (n=6) rats. Diabetes was induced in the overnight fasted rats by intramuscular injection of streptozotocin (50 mg/kg body weight). The MC extract (50 mg/kg body weight) was administered via oral gavage. Both the kidneys were collected on the tenth day following treatment. Histological study using Verhoeff's van Gieson (VvG) and Periodic Acid-Schiff (PAS) stains were performed. The kidneys of the diabetic rats showed thickening of the basement membrane of the Bowman's capsule, edema and hypercellurarity of the proximal tubules, necrosis and hyaline deposits. These features were found to be reversed when the MC extract was administered to the experimental animals. The MC extract acted as an antioxidant thereby preventing the oxidative damage involved in the diabetic kidney. The administration of MC extract prevents oxidative damage in diabetic nephropathy.

  8. Awareness level of kidney functions and diseases among adults in a Nigerian population

    PubMed Central

    Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

    2015-01-01

    The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

  9. Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats

    PubMed Central

    2013-01-01

    Background The metabolic syndrome (MS) is characterized by variable coexistence of metabolic and pathophysiological alterations which are important risk factors for developing of type II diabetes and/or cardiovascular diseases. Increased of MS patients in worldwide has stimulated the development of experimental models. However, it is still challenging to find an dietetic model that most closely approximates human MS and, in addition, is not yet fully established the effect of different diets of MS in lipid metabolism in rats of different ages. The aim of this study was to evaluate the effect of different diets of MS in lipid metabolism and ectopic fat deposition and define the most appropriate diet for inducing the characteristic disturbances of the human MS in rats of different ages. Methods Young (4 weeks old) and adult rats (12 weeks old) were given a high-fat (FAT) or high-fructose diet (FRU) for 13 weeks and biochemical, physiological, histological and biometric parameters were evaluated. Results In young rats, the FAT diet induced increased mean blood pressure (MAP) and heart rate (HR), body weight after 6 to 10 weeks, and in the 13th week, increased the liver, mesenteric, retroperitoneal and epididymal fat weights, fasting glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduced HDL cholesterol; and also induced non-alcoholic fatty liver disease (NAFLD) and renal inflammatory infiltrates. In adult rats, the FRU diet induced transient elevations of MAP and HR in the 6th week, and, at 13 weeks, increased fasting glucose, triglycerides, total cholesterol, AST and ALT; increased liver, kidneys and retroperitoneal fat weights; and induced macrovesicular and microvesicular NAFLD, the presence of fat cells in the kidney, glomerular sclerosis, and liver and kidney inflammation. Additionally, the FAT and FRU diets induced, respectively, increases in liver glycogen in adults and young rats. Conclusions Our data show that FRU diet

  10. Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats.

    PubMed

    de Castro, Uberdan Guilherme Mendes; dos Santos, Robson Augusto Souza; Silva, Marcelo Eustáquio; de Lima, Wanderson Geraldo; Campagnole-Santos, Maria José; Alzamora, Andréia Carvalho

    2013-09-18

    The metabolic syndrome (MS) is characterized by variable coexistence of metabolic and pathophysiological alterations which are important risk factors for developing of type II diabetes and/or cardiovascular diseases. Increased of MS patients in worldwide has stimulated the development of experimental models. However, it is still challenging to find an dietetic model that most closely approximates human MS and, in addition, is not yet fully established the effect of different diets of MS in lipid metabolism in rats of different ages. The aim of this study was to evaluate the effect of different diets of MS in lipid metabolism and ectopic fat deposition and define the most appropriate diet for inducing the characteristic disturbances of the human MS in rats of different ages. Young (4 weeks old) and adult rats (12 weeks old) were given a high-fat (FAT) or high-fructose diet (FRU) for 13 weeks and biochemical, physiological, histological and biometric parameters were evaluated. In young rats, the FAT diet induced increased mean blood pressure (MAP) and heart rate (HR), body weight after 6 to 10 weeks, and in the 13th week, increased the liver, mesenteric, retroperitoneal and epididymal fat weights, fasting glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduced HDL cholesterol; and also induced non-alcoholic fatty liver disease (NAFLD) and renal inflammatory infiltrates. In adult rats, the FRU diet induced transient elevations of MAP and HR in the 6th week, and, at 13 weeks, increased fasting glucose, triglycerides, total cholesterol, AST and ALT; increased liver, kidneys and retroperitoneal fat weights; and induced macrovesicular and microvesicular NAFLD, the presence of fat cells in the kidney, glomerular sclerosis, and liver and kidney inflammation. Additionally, the FAT and FRU diets induced, respectively, increases in liver glycogen in adults and young rats. Our data show that FRU diet in adult rats causes biggest change on

  11. The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats.

    PubMed

    Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P; Schreuder, Michiel F

    2016-01-01

    Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. © 2016 S. Karger AG, Basel.

  12. Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats.

    PubMed

    Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

    2014-04-01

    Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney.

  13. Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats

    PubMed Central

    Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

    2014-01-01

    Background & objectives: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. Results: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. Interpretation & conclusions: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney. PMID:24927349

  14. Effects of Dietary Calcium Supplementation on Bone Metabolism, Kidney Mineral Concentrations, and Kidney Function in Rats Fed a High-Phosphorus Diet.

    PubMed

    Katsumata, Shinichi; Matsuzaki, Hiroshi; Uehara, Mariko; Suzuki, Kazuharu

    2015-01-01

    We investigated the effects of dietary calcium (Ca) supplementation on bone metabolism, kidney mineral concentrations, and kidney function in rats fed a high-phosphorus (P) diet. Wistar strain rats were randomly divided into 4 dietary groups and fed their respective diets for 21 d: a diet containing 0.3% P and 0.5% Ca (C), a diet containing 1.5% P and 0.5% Ca (HP), a diet containing 0.3% P and 1.0% Ca (HCa), or a diet containing 1.5% P and 1.0% Ca (HPCa). Compared to the C group, the high-P diet increased serum parathyroid hormone concentration, markers of bone turnover, receptor activator of NF-κB ligand mRNA expression of the femur, kidney Ca and P concentrations, urinary N-acetyl-β-D-glucosaminidase activity, and urinary β2-microglobulin excretion, and decreased bone mineral content and bone mineral density of the femur and tibia. Dietary Ca supplementation improved the parameters of bone metabolism and kidney function in rats fed the high-P diet, while there were no significant differences in kidney Ca or P concentrations between the HP and HPCa groups. These results suggest that dietary Ca supplementation prevented the bone loss and decline in kidney function induced by a high-P diet, whereas dietary Ca supplementation did not affect kidney mineral concentrations in rats fed the high-P diet.

  15. Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure.

    PubMed

    Boon, Ai-Ching; Lam, Alfred K; Gopalan, Vinod; Benzie, Iris F; Briskey, David; Coombes, Jeff S; Fassett, Robert G; Bulmer, Andrew C

    2015-10-26

    Mildly elevated bilirubin is associated with a reduction in the presence and progression of chronic kidney disease and related mortality, which may be attributed to bilirubin's antioxidant properties. This study investigated whether endogenously elevated bilirubin would protect against adenine-induced kidney damage in male hyperbilirubinaemic Gunn rats and littermate controls. Animals were orally administered adenine or methylcellulose solvent (vehicle) daily for 10 days and were then monitored for 28 days. Serum and urine were assessed throughout the protocol for parameters of kidney function and antioxidant/oxidative stress status and kidneys were harvested for histological examination upon completion of the study. Adenine-treated animals experienced weight-loss, polyuria and polydipsia; however, these effects were significantly attenuated in adenine-treated Gunn rats. No difference in the presence of dihydroadenine crystals, lymphocytic infiltration and fibrosis were noted in Gunn rat kidneys versus controls. However, plasma protein carbonyl and F2-isoprostane concentrations were significantly decreased in Gunn rats versus controls, with no change in urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine or kidney tissue F2-isoprostane concentrations. These data indicated that endogenously elevated bilirubin specifically protects from systemic oxidative stress in the vascular compartment. These data may help to clarify the protective relationship between bilirubin, kidney function and cardiovascular mortality in clinical investigations.

  16. Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure

    PubMed Central

    Boon, Ai-Ching; Lam, Alfred K.; Gopalan, Vinod; Benzie, Iris F.; Briskey, David; Coombes, Jeff S.; Fassett, Robert G.; Bulmer, Andrew C.

    2015-01-01

    Mildly elevated bilirubin is associated with a reduction in the presence and progression of chronic kidney disease and related mortality, which may be attributed to bilirubin’s antioxidant properties. This study investigated whether endogenously elevated bilirubin would protect against adenine-induced kidney damage in male hyperbilirubinaemic Gunn rats and littermate controls. Animals were orally administered adenine or methylcellulose solvent (vehicle) daily for 10 days and were then monitored for 28 days. Serum and urine were assessed throughout the protocol for parameters of kidney function and antioxidant/oxidative stress status and kidneys were harvested for histological examination upon completion of the study. Adenine-treated animals experienced weight-loss, polyuria and polydipsia; however, these effects were significantly attenuated in adenine-treated Gunn rats. No difference in the presence of dihydroadenine crystals, lymphocytic infiltration and fibrosis were noted in Gunn rat kidneys versus controls. However, plasma protein carbonyl and F2-isoprostane concentrations were significantly decreased in Gunn rats versus controls, with no change in urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine or kidney tissue F2-isoprostane concentrations. These data indicated that endogenously elevated bilirubin specifically protects from systemic oxidative stress in the vascular compartment. These data may help to clarify the protective relationship between bilirubin, kidney function and cardiovascular mortality in clinical investigations. PMID:26498893

  17. Measurement of kidney stone formation in the rat model using micro-computed tomography

    NASA Astrophysics Data System (ADS)

    Umoh, Joseph U.; Pitelka, Vasek; Goldberg, Harvey A.; Holdsworth, David W.

    2012-03-01

    Kidney stones were induced in 5 rats by treating them with 1% ethylene glycol and 1% ammonium chloride through free drinking water for six weeks. The animals were anesthetized and imaged in vivo before the treatment at week 0, to obtain baseline data, then at weeks 2 and 6 to monitor the kidney stone formation. Micro-CT imaging was performed with x-ray tube voltage of 90 kV and a current of 40 mA. At week 2, kidney stone formation was observed. A micro-computed tomography methodology of estimating the volume and hydroxyapatite-equivalent mineral content of the kidney stone is presented. It determines the threshold CT number (390 HU) that separates the kidney stone from the tissue. The mean volume of the stones in the 10 kidneys significantly increased from 3.81+/-0.72 mm3 at week 2 to 23.96+/-9.12 mm3 at week 6 (p<0.05, r2=0.34). Measurement precision error was about 4%. This method allows analysis of the kidney stone formation to be carried out in vivo, with fewer experimental animals compared with other ex vivo methods, in which animals are sacrificed. It is precise, accurate, non-destructive, and could be used in pre-clinical research to study the formation of kidney stones in live small animals.

  18. Histopathological changes in liver, kidney and muscles of pesticides exposed malnourished and diabetic rats.

    PubMed

    Benjamin, Nidhi; Kushwah, Ameeta; Sharma, R K; Katiyar, A K

    2006-03-01

    Histopathological changes were observed in liver, kidney and muscles of normal, protein-malnourished, diabetic as well as both protein-malnourished and diabetic albino rats when exposed to a mixture of monocrotophos, hexachlorocyclohexane and endosulfan at varying intervals. The examination revealed hepatotoxic, nephrotoxic and muscular necrotic effects in pesticides exposed rats. Toxicity was aggravated in protein-malnourished and diabetic animals and more so, if the animals were both diabetic and protein-malnourished.

  19. Effects of grape seed proanthocyanidin extract on oxidative stress induced by diabetes in rat kidney.

    PubMed

    Mansouri, Esrafil; Panahi, Marzieh; Ghaffari, Mohammad Ali; Ghorbani, Ali

    2011-01-01

    This study examined the effect of grape seed proanthocyanidin extract (GSPE) on lipid peroxidation content and activity of tissue antioxidant enzymes, including catalase, superoxide dismutase and glutathione peroxidase in diabetic rats. Thirty male rats were divided into three groups of 10 rats each: control, diabetic and diabetic groups that received 500 mg/kg GSPE for 6 weeks. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Rats with fasting blood glucose levels above 250 mg/dl were used as diabetic animals. The first 24-hour urinary albumin excretion (UAE) was measured two weeks after diabetes induction and then each week until the end of the experimental period in all groups. Lipid peroxidation content and activities of catalase, superoxide dismutase and glutathione peroxidase were measured in kidney homogenate supernatants. Statistical significance of differences was assessed with one-way ANOVA by SPSS followed by Tukey's t-test. P < 0.05 was assumed statistically significant. UAE in diabetic nephropathy rats were significantly higher than in control. In addition, an increase in lipid peroxidation content and decrease in catalase, superoxide dismutase and glutathione peroxidase activities in kidney of diabetic nephropathy rats were observed. The GSPE administration did not affect on body weight, but significantly decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in kidney of diabetic nephropathy rats as well as reduced UAE and decreased kidney weight. The results suggested that GSPE could ameliorate diabetic nephropathy rats through reduction of oxidative stress and increase in renal antioxidant enzyme activity.

  20. [Effects of activating silent information regulator 1 on early kidney damage in rats with severe burn].

    PubMed

    Bai, X Z; He, T; Liu, Y; Zhang, W; Han, F; Yang, C; Cai, W X; Jia, Y H; Shi, J H; Han, J T; Su, L L; Hu, D H

    2017-06-20

    Objective: To investigate the effects of activating silent information regulator 1 (SIRT1) on the early kidney damage in rats with severe burn. Methods: Thirty healthy male SD rats were divided into sham injury group (SI), pure burn group (PB), and SIRT1 activator group (SA) according to the random number table, with 10 rats in each group. Rats in groups PB and SA were inflicted with 30% total body surface area full-thickness scald (hereinafter referred to as burn) on the back. Immediately after injury, rats in group PB were intraperitoneally injected with normal saline in the dosage of 50 mL/kg, and those in group SA with 1 mg/mL (final mass concentration) resveratrol in the dosage of 50 mL/kg. Rats in group SI were sham injured and intraperitoneally injected with normal saline in the dosage of 50 mL/kg immediately after injury. Kidney tissue and abdominal aorta blood of rats in the three groups were collected at 24 hours after injury. The morphology of kidney tissue was observed after HE staining. The serum content of creatinine and urea nitrogen was determined with enzyme-linked immunosorbent assay. Protein expressions of SIRT1, Bax, and Bcl-2 in kidney tissue were determined with Western blotting. mRNA expressions of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-10 in kidney tissue were determined with real-time fluorescent quantitative reverse transcription polymerase chain reaction. Data were processed with one-way analysis of variance and LSD-t test. Results: (1) In rats of group SI, structures of kidney tubules and glomeruli were intact. In rats of group PB, structures of kidney tubules were not clear with casts in them, and glomeruli showed pyknosis. In rats of group SA, structures of kidney tubules were relatively intact, and the pyknosis of glomeruli were slighter as compared with that of group PB with fewer glomeruli showing pyknosis. (2) The serum content of creatinine and urea nitrogen in rats of group PB was (67±14)

  1. Iron therapy in anaemic adults without chronic kidney disease.

    PubMed

    Gurusamy, Kurinchi Selvan; Nagendran, Myura; Broadhurst, Jack F; Anker, Stefan D; Richards, Toby

    2014-12-31

    Anaemia affects about a quarter of the world's population. An estimated 50% of anaemic people have anaemia due to iron deficiency. To assess the safety and efficacy of iron therapies for the treatment of adults with anaemia who are not pregnant or lactating and do not have chronic kidney disease. We ran the search on 11 July 2013. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE (Ovid SP), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus (EBSCO Host), the Institute for Scientific Information Web of Science (ISI WOS) Scientific Citation Index (SCI)-EXPANDED (1970) and Conference Proceedings Citation Index (CPCI)-Science (1990) and Clinicaltrials.gov; we also screened reference lists. An updated search was run on 24 November 2014 but the results have not yet been incorporated into the review. Two review authors independently selected references for further assessment by going through all titles and abstracts. Further selection was based on review of full-text articles for selected references. Two review authors independently extracted study data. We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary outcomes and the mean difference (MD) or the standardised mean difference (SMD) with 95% CI for continuous outcomes. We performed meta-analysis when possible, when I(2) was less than or equal to 80% using a fixed-effect or random-effects model, using Review Manager software. The range of point estimates for individual studies is presented when I(2) > 80%. We included in this systematic review 4745 participants who were randomly assigned in 21 trials. Trials were conducted in a wide variety of clinical settings. Most trials included participants with mild to moderate anaemia and excluded participants who were allergic to iron therapy. All trials were at high risk of bias for one or more domains. We compared both oral iron and parenteral iron versus inactive controls and compared

  2. Gene expression profiling in rat kidney after intratracheal exposure to cadmium-doped nanoparticles

    NASA Astrophysics Data System (ADS)

    Coccini, Teresa; Roda, Elisa; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Manzo, Luigi

    2012-08-01

    While nephrotoxicity of cadmium is well documented, very limited information exists on renal effects of exposure to cadmium-containing nanomaterials. In this work, "omics" methodologies have been used to assess the action of cadmium-containing silica nanoparticles (Cd-SiNPs) in the kidney of Sprague-Dawley rats exposed intratracheally. Groups of animals received a single dose of Cd-SiNPs (1 mg/rat), CdCl2 (400 μg/rat) or 0.1 ml saline (control). Renal gene expression was evaluated 7 and 30 days post exposure by DNA microarray technology using the Agilent Whole Rat Genome Microarray 4x44K. Gene modulating effects were observed in kidney at both time periods after treatment with Cd-SiNPs. The number of differentially expressed genes being 139 and 153 at the post exposure days 7 and 30, respectively. Renal gene expression changes were also observed in the kidney of CdCl2-treated rats with a total of 253 and 70 probes modulated at 7 and 30 days, respectively. Analysis of renal gene expression profiles at day 7 indicated in both Cd-SiNP and CdCl2 groups downregulation of several cluster genes linked to immune function, oxidative stress, and inflammation processes. Differing from day 7, the majority of cluster gene categories modified by nanoparticles in kidney 30 days after dosing were genes implicated in cell regulation and apoptosis. Modest renal gene expression changes were observed at day 30 in rats treated with CdCl2. These results indicate that kidney may be a susceptible target for subtle long-lasting molecular alterations produced by cadmium nanoparticles locally instilled in the lung.

  3. Taurine decreased uric acid levels in hyperuricemic rats and alleviated kidney injury.

    PubMed

    Feng, Ying; Sun, Fang; Gao, Yongchao; Yang, Jiancheng; Wu, Gaofeng; Lin, Shumei; Hu, Jianmin

    2017-07-29

    Hyperuricemia can lead to direct kidney damage. Taurine participates in several renal physiological processes and has been shown as a renoprotective agent. It has been reported that taurine could reduce uric acid levels in diabetic rats, but to date there was no research on the effects of taurine on hyperuricemic rats with kidney injury. In present study, hyperuricemic rat models were induced by intragastric administration of adenine and ethambutol hydrochloride for 10 days, and taurine (1% or 2%) were added in the drinking water 7 days in advance for consecutively 17 days. The results showed that taurine alleviated renal morphological and pathological changes as well as kidney dysfunction in hyperuricemic rats. Taurine could efficiently decrease the elevated xanthine oxidase activities in hyperuricemic rats, indicating its effect on the regulation of uric acid formation. The reabsorption and secretion of uric acid are dependent on a number of urate transporters. Expressions of three urate transporters were significantly down-regulated in hyperuricemic rats, while taurine prevented the decrease of mRNA and protein expression levels of these urate transporters. The results indicate that taurine might play a role in the regulation of renal uric acid excretion. Therefore, taurine could be a promising agent for the treatment of hyperuricemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Exhaustive swimming exercise related kidney injury in rats - protective effects of acetylbritannilactone.

    PubMed

    Wu, G L; Chen, Y S; Huang, X D; Zhang, L X

    2012-01-01

    The aim of this study was to investigate the protective effects of acetylbritannilactone (ABL) on renal injury induced by acute exhaustive exercise in the rat. The exhaustive exercise induced kidney injury in rats was established by exhaustive swimming (ES). ABL (26 mg/kg) or polyglycol (control) were administrated orally by gastric gavage 24 h before training. Renal function, biochemical index, renal histopathological change, oxidative stress indices, renal cell apoptosis and inflammatory molecules were checked after ES, for 6 h and 24 h. It was found that immediately after exhaustive swimming, the serum urea and creatinine were significantly higher in ES rats, and the same for serum creatine kinase. All the values were reduced in the ES rats treated with ABL. The increase of superoxide dismutase activity and decrease of malondialdehyde content in the kidney were found in rats with ABL treatment. Tubular cell apoptosis at different time points after ES were significantly reduced by the ABL treatment. The increased expression of TNF-α and NF-κB induced by ES was also significantly decreased by ABL treatment. Our results suggest that ABL protects rats from overtraining-induced kidney injury by inhibiting renal cell apoptosis and suppressing oxidative-stress generation and inhibiting inflammation. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Kidney-Tonifying Recipe Can Repair Alterations in Adrenal Medullary Chromaffin Cells in Asthmatic Rats

    PubMed Central

    Hu, Cheng-Ping; Zou, Jun-Tao; Zou, Ye-Qiang; Li, Xiao-Zhao; Feng, Jun-Tao

    2012-01-01

    Traditional Chinese medicine suggests that renal deficiency is a causative factor of asthma, and tonifying kidney drugs are believed to be an appropriate and beneficial treatment. The adrenal medullary chromaffin cells (AMCC) transition to the neuronal phenotype is known to occur in asthma, as evidenced by degranulation of chromaffin granules, decline of epinephrine (EPI) and phenylethanolamine-n-methyl transferase (PNMT), and obvious alterations in cellular architecture. In this study, rats were sensitized and challenged with ovalbumin, then treated with Kidney-Tonifying Recipe (KTR) to evaluate the therapeutic effect. Tissues were evaluated for changes in pathology and EPI, PNMT, and peripherin expression. Degranulation of chromaffin granules and appearance of neurite-like process were found in AMCC from asthmatic rats, and these changes were corrected by KTR treatment. EPI and PNMT expressions were decreased in asthmatic rats and increased by KTR treatment. Peripherin expression was increased in asthmatic rats and decreased in the KTR-treated group. Morphological changes and decreases in EPI were observed when cultured AMCC were exposed to sera from asthmatic rats in vitro, and these changes were attenuated with the addition of sera from KRT-treated rats. These results suggest that the Kidney-Tonifying Recipe is capable of repairing asthma-associated alterations in endocrine function and the ultrastructure of AMCC. PMID:22474509

  6. Decellularized scaffold of cryopreserved rat kidney retains its recellularization potential

    PubMed Central

    Chani, Baldeep; Puri, Veena; Sobti, Ranbir C.; Jha, Vivekanand; Puri, Sanjeev

    2017-01-01

    The multi-cellular nature of renal tissue makes it the most challenging organ for regeneration. Therefore, till date whole organ transplantations remain the definitive treatment for the end stage renal disease (ESRD). The shortage of available organs for the transplantation has, thus, remained a major concern as well as an unsolved problem. In this regard generation of whole organ scaffold through decellularization followed by regeneration of the whole organ by recellularization is being viewed as a potential alternative for generating functional tissues. Despite its growing interest, the optimal processing to achieve functional organ still remains unsolved. The biggest challenge remains is the time line for obtaining kidney. Keeping these facts in mind, we have assessed the effects of cryostorage (3 months) on renal tissue architecture and its potential for decellularization and recellularization in comparison to the freshly isolated kidneys. The light microscopy exploiting different microscopic stains as well as immuno-histochemistry and Scanning electron microscopy (SEM) demonstrated that ECM framework is well retained following kidney cryopreservation. The strength of these structures was reinforced by calculating mechanical stress which confirmed the similarity between the freshly isolated and cryopreserved tissue. The recellularization of these bio-scaffolds, with mesenchymal stem cells quickly repopulated the decellularized structures irrespective of the kidneys status, i.e. freshly isolated or the cryopreserved. The growth pattern employing mesenchymal stem cells demonstrated their equivalent recellularization potential. Based on these observations, it may be concluded that cryopreserved kidneys can be exploited as scaffolds for future development of functional organ. PMID:28267813

  7. Altered heart and kidney phospholipid fatty acid composition are associated with cardiac hypertrophy in hypertensive rats.

    PubMed

    Kim, Oh Yoen; Jung, Young-Sang; Cho, Yoonsu; Chung, Ji Hyung; Hwang, Geum-Sook; Shin, Min-Jeong

    2013-08-01

    We examined the association of cardiac hypertrophy or fibrosis with the phospholipid fatty acid (FA) composition of heart and kidney in hypertensive rats. Eight-week-old spontaneously hypertensive rats (SHRs) (n=8) and Wistar Kyoto rats (WKYs, n=8) as a normotensive control, were fed ad libitum for 6 weeks with regular AIN-76 diet. Phospholipid FA compositions in the left ventricle and kidney were measured and histological analyses were performed. Compared with WKYs, SHRs had lower proportions of γ-linolenic acid, α-linolenic acid, eicosadienoic acid, eicosatrienoic acid, dihomo-γ-linoleic acid, docosadienoic acid and nervonic acid in heart, and stearic acid (SA), γ-linolenic acid, and eicosapentaenoic acid (EPA) in kidney. After adjusting for food intake, SHRs still maintained higher proportions of SA, and total saturated FAs in the heart and a lower proportion of eicosapentaenoic acid in the kidney. Additionally, compared with WKYs, SHRs showed larger cardiomyocyte diameters in the left ventricles, indicating cardiac hypertrophy and interstitial fibrosis. Cardiomyocyte diameters also positively correlated with cardiac SA (r=0.550, p<0.05) and negatively with kidney EPA (r=-0.575, p<0.05). Tissue FA compositions were associated with cardiac hypertrophy in a hypertensive setting, implicating the pathogenic role of tissue FAs in hypertension and related complications. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  8. Evaluation of kidney injury biomarkers in rat amniotic fluid after gestational exposure to cadmium.

    PubMed

    Jacobo-Estrada, Tania; Cardenas-Gonzalez, Mariana; Santoyo-Sánchez, Mitzi; Parada-Cruz, Benjamín; Uria-Galicia, Esther; Arreola-Mendoza, Laura; Barbier, Olivier

    2016-09-01

    Cadmium is a well-characterized nephrotoxic agent that is also capable of accumulating and diffusing across the placenta; however, only a few studies have addressed its effects over fetal kidneys and none of them has used a panel of sensitive and specific biomarkers for the detection of kidney injury. The goal of this study was to determine cadmium renal effects in rat fetuses by the quantification of early kidney injury biomarkers. Pregnant Wistar rats were exposed by inhalation to an isotonic saline solution or to CdCl2 solution (DDel =1.48 mg Cd kg(-1) day(-1) ) during gestational days (GD) 8-20. On GD 21, dams were euthanized and samples obtained. Kidney injury biomarkers were quantified in amniotic fluid samples and fetal kidneys were microscopically evaluated to search for histological alterations. Our results showed that cadmium exposure significantly raised albumin, osteopontin, vascular endothelial growth factor and tissue inhibitor of metalloproteinases-1 levels in amniotic fluid, whereas it decreased creatinine. Clusterin, calbindin and IFN-inducible protein 10 did not show any change. Accordingly, histological findings showed tubular damage and precipitations in the renal pelvis. In conclusion, gestational exposure to cadmium induces structural alterations in fetal renal tissue that can be detected by some kidney injury biomarkers in amniotic fluid samples. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Novel therapeutic approaches of natural oil from black seeds and its underlying mechanisms against kidney dysfunctions in haloperidol-induced male rats.

    PubMed

    Akintunde, Jacob K; Abubakar, Opeyemi K

    2017-05-24

    Antipsychotic drugs could be nephrotoxic in schizophrenia patients. The present study investigated the protective effect of oil from black seed on kidney dysfunctions using several biological approaches in adult rats. The animals were divided into six groups (n=10): normal control rats; haloperidol (HAL)-induced rats: induced rats were pre-, co- and post-treated with black seed oil (BSO), respectively, and the last group was treated with the oil only. The treatment was done through oral administration, and the experiment lasted 14 days. Therapeutic administration of HAL to rats caused reduction in both enzymatic and non-enzymatic proteins mediated by stable OH˙ and DPPH free radicals. K+, Na+ and MDA contents as well as 51 nucleotidase, aldose-reductase activities were increased with corresponding decrease in the activity of lactate dehydrogenase (LDH) in HAL-induced toxicity rats. Contrariwise, differential treatments with BSO prevented and reversed the nephrotoxicity by depleting K+, Na+, MDA contents and aldose-reductase activity, and AMP hydrolysis with increased adenosine triphosphate (ATP) in the PMFs of rat kidney. The cytotoxicity of HAL elicited on both inner renal cortex and outer medulla was equally alleviated by combined active molecules of oil from black seed (OBS). However, pre-, co- and post-treatment demonstrate significant approaches in averting nephrotoxicity of neuroleptic drug (HAL) via several biological mechanisms. This study therefore validates the use of black seed oil as therapy particularly for individuals with renal dysfunctions.

  10. The Emergence of Kidney Stone Disease During Childhood-Impact on Adults.

    PubMed

    Bonzo, Jeremy R; Tasian, Gregory E

    2017-06-01

    The goal of this chapter is to review the recent epidemiologic trends of kidney stone disease and discuss the impact of the increasing incidence of nephrolithiasis among children on adults with respect to extra-renal manifestations, surgical management, and secondary prevention. Among pediatric patients, kidney stone disease has been increasing at a rate of approximately 5-10% annually. Kidney stone disease has been associated with increased risks of coronary heart disease, chronic kidney disease, hypertension, and decreased bone mineral density, which is concerning for patients diagnosed at a young age. Improvements in endo-urology have allowed for less invasive surgical treatment of stones in the pediatric population. However, current guidelines often lack recommendations for evaluation, medical, and surgical management of children with kidney stone disease. Nephrolithiasis is a disorder of mineral metabolism, which is beginning during childhood with increasing frequency. Kidney stone disease often exists over the lifetime and is associated with serious conditions that are important for pediatric and adult urologists to recognize and consider in their evaluation and treatment of patients.

  11. Sex differences in kidney gene expression during the life cycle of F344 rats.

    PubMed

    Kwekel, Joshua C; Desai, Varsha G; Moland, Carrie L; Vijay, Vikrant; Fuscoe, James C

    2013-07-31

    The kidney functions in key physiological processes to filter blood and regulate blood pressure via key molecular transporters and ion channels. Sex-specific differences have been observed in renal disease incidence and progression, as well as acute kidney injury in response to certain drugs. Although advances have been made in characterizing the molecular components involved in various kidney functions, the molecular mechanisms responsible for sex differences are not well understood. We hypothesized that the basal expression levels of genes involved in various kidney functions throughout the life cycle will influence sex-specific susceptibilities to adverse renal events. Whole genome microarray gene expression analysis was performed on kidney samples collected from untreated male and female Fischer 344 (F344) rats at eight age groups between 2 and 104 weeks of age. A combined filtering approach using statistical (ANOVA or pairwise t test, FDR 0.05) and fold-change criteria (>1.5 relative fold change) was used to identify 7,447 unique differentially expressed genes (DEGs). Principal component analysis (PCA) of the 7,447 DEGs revealed sex-related differences in mRNA expression at early (2 weeks), middle (8, 15, and 21 weeks), and late (104 weeks) ages in the rat life cycle. Functional analysis (Ingenuity Pathway Analysis) of these sex-different genes indicated over-representation of specific pathways and networks including renal tubule injury, drug metabolism, and immune cell and inflammatory responses. The mRNAs that code for the qualified urinary protein kidney biomarkers KIM-1, Clu, Tff3, and Lcn2 were also observed to show sex differences. These data represent one of the most comprehensive in-life time course studies to be published, assessing sex differences in global gene expression in the F344 rat kidney. PCA and Venn analyses reveal specific periods of sexually dimorphic gene expression which are associated with functional categories (xenobiotic

  12. Sex differences in kidney gene expression during the life cycle of F344 rats

    PubMed Central

    2013-01-01

    Background The kidney functions in key physiological processes to filter blood and regulate blood pressure via key molecular transporters and ion channels. Sex-specific differences have been observed in renal disease incidence and progression, as well as acute kidney injury in response to certain drugs. Although advances have been made in characterizing the molecular components involved in various kidney functions, the molecular mechanisms responsible for sex differences are not well understood. We hypothesized that the basal expression levels of genes involved in various kidney functions throughout the life cycle will influence sex-specific susceptibilities to adverse renal events. Methods Whole genome microarray gene expression analysis was performed on kidney samples collected from untreated male and female Fischer 344 (F344) rats at eight age groups between 2 and 104 weeks of age. Results A combined filtering approach using statistical (ANOVA or pairwise t test, FDR 0.05) and fold-change criteria (>1.5 relative fold change) was used to identify 7,447 unique differentially expressed genes (DEGs). Principal component analysis (PCA) of the 7,447 DEGs revealed sex-related differences in mRNA expression at early (2 weeks), middle (8, 15, and 21 weeks), and late (104 weeks) ages in the rat life cycle. Functional analysis (Ingenuity Pathway Analysis) of these sex-different genes indicated over-representation of specific pathways and networks including renal tubule injury, drug metabolism, and immune cell and inflammatory responses. The mRNAs that code for the qualified urinary protein kidney biomarkers KIM-1, Clu, Tff3, and Lcn2 were also observed to show sex differences. Conclusions These data represent one of the most comprehensive in-life time course studies to be published, assessing sex differences in global gene expression in the F344 rat kidney. PCA and Venn analyses reveal specific periods of sexually dimorphic gene expression which are associated with

  13. Blood pressure, blood flow, and oxygenation in the clipped kidney of chronic 2-kidney, 1-clip rats: effects of tempol and Angiotensin blockade.

    PubMed

    Palm, Fredrik; Onozato, Maristela; Welch, William J; Wilcox, Christopher S

    2010-02-01

    Angiotensin II maintains renal cortical blood flow and renal oxygenation in the clipped kidney of early 2-kidney, 1-clip Goldblatt hypertensive (2K,1C) rats. The involvement of Ang II is believed to decline, whereas oxidative stress increases during the progression of 2K,1C hypertension. We investigated the hypothesis that the acute administration of drugs to inhibit reactive oxygen species (Tempol), angiotensin II type 1 receptors (candesartan), or angiotensin-converting enzyme (enalaprilat) lowers mean arterial pressure and increases kidney blood flow and oxygenation in the clipped kidney of chronic 2K,1C rats in contrast to sham controls. Twelve months after left renal artery clipping or sham, mean arterial pressure, renal cortical blood flow, and renal cortical and medullary oxygen tension were measured after acute administration of Tempol followed by enalaprilat or candesartan followed by enalaprilat. The mean arterial pressure of the 2K,1C rat was reduced by candesartan (-9%) and, more effectively, by Tempol (-35%). All of the applied treatments had similar blood pressure-lowering effects in sham rats (average: -21%). Only Tempol increased cortical blood flow (+35%) and cortical and medullary oxygen tensions (+17% and +94%, respectively) in clipped kidneys of 2K,1C rats. Administration of enalaprilat had no additional effect, except for a modest reduction in cortical blood flow in the clipped kidney of 2K,1C rats when coadministered with candesartan (-10%). In conclusion, acute administration of Tempol is more effective than candesartan in reducing the mean arterial blood pressure and improving renal blood perfusion and oxygenation in the clipped kidney of chronic 2K,1C rats.

  14. Hydrogen sulfide ameliorates the kidney dysfunction and damage in cisplatin-induced nephrotoxicity in rat

    PubMed Central

    Ahangarpour, Akram; Abdollahzade Fard, Amin; Gharibnaseri, Mohammad Kazem; Jalali, Taha; Rashidi, Iran

    2014-01-01

    Hydrogen Sulfide (H2S) prevents and treats a variety of disorders via its cytoprotective effects. However, the effects of H2S on rats with cisplatin (CP) nephrotoxicity are unclear. The aim was to study the effects of H2S on rats with CP nephrotoxicity. Thirty male Sprague-Dawley rats were divided into three groups: control group, nephrotoxic group received single dose of CP (6 mg kg-1) and nephrotoxic groups that received single dose 100 µmol kg-1 NaHS. On fifth day after injection, urine of each rat was collected over a 24-hr period. Animals were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and kidneys were obtained, prepared for light microscopy evaluation, lipid peroxidation content and laboratory analysis. The results showed that plasma urea (226%), creatinine (271%), renal lipid peroxidation content (151%), Na and K fractional excretion, urine protein, volume and kidney weight in CP nephrotoxic rats were significantly higher and urine osmolarity and creatinine clearance lower than in controls. Increases of the proximal tubular cells apoptosis and mesangial matrix in CP nephrotoxicity group rats were observed. Hydrogen sulfide reversed the CP-induced changes in the experimental rats H2S prevented the progression of CP nephrotoxicity in rats possibly through its cytoprotective effects such as antioxidant properties. PMID:25568705

  15. BROMATE-INDUCED TRANSCRIPTIONAL CHANGES IN LONG-EVANS RAT KIDNEYS

    EPA Science Inventory


    Bromate-Induced Transcriptional Changes in Long-Evans Rat Kidneys.

    Ozone disinfection of surface waters containing bromide ion (Br-) results in the oxidation of bromide to bromate, which can be found in finished drinking water as a by-product. Potassium bromate (KBrO3)...

  16. BROMATE-INDUCED TRANSCRIPTIONAL CHANGES IN LONG-EVANS RAT KIDNEYS

    EPA Science Inventory


    Bromate-Induced Transcriptional Changes in Long-Evans Rat Kidneys.

    Ozone disinfection of surface waters containing bromide ion (Br-) results in the oxidation of bromide to bromate, which can be found in finished drinking water as a by-product. Potassium bromate (KBrO3)...

  17. Differential changes in atrial natriuretic peptide and vasopressin receptor bindings in kidney of spontaneously hypertensive rat

    SciTech Connect

    Ogura, T.; Mitsui, T.; Yamamoto, I.; Katayama, E.; Ota, Z.; Ogawa, N.

    1987-01-19

    To elucidate the role of atrial natriuretic peptide (ANP) and vasopressin (VP) in a hypertensive state, ANP and VP receptor bindings in spontaneously hypertensive rat (SHR) kidney were analyzed using the radiolabeled receptor assay (RRA) technique. Systolic blood pressure of SHR aged 12 weeks was statistically higher than that of age-matched Wistar Kyoto (WKY) rats. Maximum binding capacity (Bmax) of (/sup 125/I)-ANP binding to the SHR kidney membrane preparations was statistically lower than that of WKY rats, but dissociation constant (Kd) was not significantly different. On the other hand, Bmax of (/sup 3/H)-VP binding to the SHR kidney membrane preparations was statistically higher than that of WKY rats, but Kd were similar. Since the physiological action of ANP is natriuresis and VP is the most important antidiuretic hormone in mammalia, these opposite changes of ANP and VP receptor bindings in SHR kidney suggested that these peptides may play an important role in the pathophysiology of the hypertensive state, although it has not been confirmed as yet.

  18. Insulin-mediated oxidative stress and DNA damage in LLC-PK1 pig kidney cell line, female rat primary kidney cells, and male ZDF rat kidneys in vivo.

    PubMed

    Othman, Eman Maher; Kreissl, Michael C; Kaiser, Franz R; Arias-Loza, Paula-Anahi; Stopper, Helga

    2013-04-01

    Hyperinsulinemia, a condition with excessively high insulin blood levels, is related to an increased cancer incidence. Diabetes mellitus is the most common of several diseases accompanied by hyperinsulinemia. Because an elevated kidney cancer risk was reported for diabetic patients, we investigated the induction of genomic damage by insulin in LLC-PK1 pig kidney cells, rat primary kidney cells, and ZDF rat kidneys. Insulin at a concentration of 5nM caused a significant increase in DNA damage in vitro. This was associated with the formation of reactive oxygen species (ROS). In the presence of antioxidants, blockers of the insulin, and IGF-I receptors, and a phosphatidylinositol 3-kinase inhibitor, the insulin-mediated DNA damage was reduced. Phosphorylation of protein kinase B (PKB or AKT) was increased and p53 accumulated. Inhibition of the mitochondrial and nicotinamide adenine dinucleotide phosphatase oxidase-related ROS production reduced the insulin-mediated damage. In primary rat cells, insulin also induced genomic damage. In kidneys from healthy, lean ZDF rats, which were infused with insulin to yield normal or high blood insulin levels, while keeping blood glucose levels constant, the amounts of ROS and the tumor protein (p53) were elevated in the high-insulin group compared with the control level group. ROS and p53 were also elevated in diabetic obese ZDF rats. Overall, insulin-induced oxidative stress resulted in genomic damage. If the same mechanisms are active in patients, hyperinsulinemia might cause genomic damage through the induction of ROS contributing to the increased cancer risk, against which the use of antioxidants and/or ROS production inhibitors might exert protective effects.

  19. Cafeteria diet increases prostaglandin E2 levels in rat prostate, kidney and testis.

    PubMed

    Brunetti, L; Leone, S; Chiavaroli, A; Orlando, G; Recinella, L; Ferrante, C; Di Nisio, C; Verratti, V; Vacca, M

    2010-01-01

    Nutrient composition, particularly the omega-6/omega-3 polyunsaturated fatty acids ratio, may differently affect inflammatory mediators production in tissues, which could be causally related to increased cancer incidence in obesity. We evaluated prostaglandin E(2) levels in male Wistar rat prostate, kidney and testicle tissues after 15 days of either a high fat, cafeteria-style diet (5.50 Kcal/g, 30 percent calories from fat, omega-6/omega-3 ratio 2.33) or a standard laboratory chow diet (3.35 Kcal/g, 3 percent calories from fat, omega-6/omega-3 ratio 0.56). In the cafeteria diet compared to standard laboratory diet rats, we found both an increase in weight gain and increased prostaglandin E(2) (PGE(2)) levels in prostate, kidney and testicle tissues. The increased levels of PGE(2) induced by the cafeteria diet could drive an inflammatory process leading to increased incidence of prostate, kidney and testicular cancer in overweight patients.

  20. Thymoquinone ameliorates lead-induced suppression of the antioxidant system in rat kidneys

    PubMed Central

    Mabrouk, Aymen; Cheikh, Hassen Ben

    2016-01-01

    Objective Alteration of the antioxidant status in the kidneys may be related to lead (Pb) intoxication. The present study aimed to investigate the possible beneficial effect of thymoquinone (TQ), the major active ingredient of the volatile oil of Nigella sativa seeds, on Pb-induced renal antioxidant defense system impairment. Methods A total of thirty two healthy adult male Wistar rats were randomly divided into four equal groups as follows: a control group, which received no treatment; a Pb group, which was exposed to 2,000 ppm of Pb acetate in drinking water; a Pb-TQ group, which was cotreated with Pb plus TQ (5 mg/kg/day, per os); and a TQ group receiving only TQ. All treatments were applied for five weeks. Results TQ alone did not induce any significant changes in the antioxidant defense system. By contrast, Pb exposure significantly decreased reduced glutathione level and superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activities in the renal tissue. Interestingly, supplementation with TQ significantly improved the affected antioxidant parameters. Conclusion Our data are the first to provide evidence on the protective effect of TQ against Pb-induced renal antioxidant capacity impairment and suggest that this component might be a clinically promising alternative in Pb nephrotoxicity. PMID:27052350

  1. Transcriptome Analysis in Rat Kidneys: Importance of Genes Involved in Programmed Hypertension

    PubMed Central

    Tain, You-Lin; Huang, Li-Tung; Chan, Julie Y. H.; Lee, Chien-Te

    2015-01-01

    Suboptimal conditions in pregnancy can elicit long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether there are common genes and pathways in the kidney are responsible for generating programmed hypertension among three different models using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received dexamethasone (DEX, 0.1 mg/kg) from gestational day 16 to 22, 60% high-fructose (HF) diet, or NG-nitro-l-arginine-methyester (l-NAME, 60 mg/kg/day) to conduct DEX, HF, or l-NAME model respectively. All three models elicited programmed hypertension in adult male offspring. We observed five shared genes (Bcl6, Dmrtc1c, Egr1, Inmt, and Olr1668) among three different models. The identified differential genes (DEGs) that are related to regulation of blood pressure included Aqp2, Ptgs1, Eph2x, Hba-a2, Apln, Guca2b, Hmox1, and Npy. RNA-Seq identified genes in arachidonic acid metabolism are potentially gatekeeper genes contributing to programmed hypertension. In addition, HF and DEX increased expression and activity of soluble epoxide hydrolase (Ephx2 gene encoding protein). Conclusively, the DEGs in arachidonic acid metabolism are potentially gatekeeper genes in programmed hypertension. The roles of DEGs identified by the RNA-Seq in this study deserve further clarification, to develop the potential interventions in the prevention of programmed hypertension. PMID:25739086

  2. Methylene blue attenuates mitochondrial dysfunction of rat kidney during experimental acute pancreatitis.

    PubMed

    Kuliaviene, Irma; Baniene, Rasa; Virketyte, Simona; Kincius, Marius; Jansen, Eugene; Gulbinas, Antanas; Kupcinskas, Limas; Trumbeckaite, Sonata; Borutaite, Vilmante

    2016-03-01

    The disturbance of mitochondrial functions has been considered as one of the mechanisms of pathogenesis of acute pancreatitis (AP) followed by kidney failure. This study was aimed to investigate the effects of methylene blue (MB) on pancreas and kidney mitochondrial respiratory functions during experimental acute pancreatitis in rats. AP was induced by administrating sodium taurocholate into the pancreatic duct of male Wistar rats. The rats were divided into three groups: the MB group, MB (5 mg/kg) was injected intravenously 10 min prior to AP induction; the AP group, saline solution was injected intravenously 10 min prior to AP induction; and the sham operation group, isotonic sodium chlorine was used instead of sodium taurocholate. The animals were sacrificed after 24 h. The pancreas and kidney were removed for mitochondrial assay by oxygraphic and spectrophotometric methods. Intravenous injection of MB did not prevent AP-induced inhibition of pancreatic mitochondrial respiration; however, MB significantly improved kidney mitochondrial respiratory functions with complex I-dependent substrates glutamate and malate. The activity of complex I of mitochondria isolated from AP-damaged kidney was increased after pretreatment with MB. However, MB did not affect AP-inhibited kidney mitochondrial respiration with succinate. MB had no protective effects on amylase activity or on urea content in serum in AP. The disturbances of kidney mitochondrial energy metabolism in experimental model of severe AP can be ameliorated by MB administration. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  3. Kidney Tissue Targeted Metabolic Profiling of Unilateral Ureteral Obstruction Rats by NMR

    PubMed Central

    Li, Zhenyu; Li, Aiping; Gao, Jining; Li, Hong; Qin, Xuemei

    2016-01-01

    Renal interstitial fibrosis is a common pathological process in the progression of kidney disease. A nuclear magnetic resonance (NMR) based metabolomic approach was used to analyze the kidney tissues of rats with renal interstitial fibrosis (RIF), induced by unilateral ureteral obstruction (UUO). The combination of a variety of statistical methods were used to screen out 14 significantly changed potential metabolites, which are related with multiple biochemical processes including amino acid metabolism, adenine metabolism, energy metabolism, osmolyte change and induced oxidative stress. The exploration of the contralateral kidneys enhanced the understanding of the disease, which was also supported by serum biochemistry and kidney histopathology results. In addition, the pathological parameters (clinical chemistry, histological and immunohistochemistry results) were correlated with the significantly changed differential metabolites related with RIF. This study showed that targeted tissue metabolomic analysis can be used as a useful tool to understand the mechanism of the disease and provide a novel insight in the pathogenesis of RIF. PMID:27695416

  4. Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys.

    PubMed

    Cui, Jing; Shi, Suozhu; Sun, Xuefeng; Cai, Guangyan; Cui, Shaoyuan; Hong, Quan; Chen, Xiangmei; Bai, Xue-Yuan

    2013-01-01

    A high-calorie (HC) diet induces renal injury and promotes aging, and calorie restriction (CR) may ameliorate these responses. However, the effects of long-term HC and CR on renal damage and aging have been not fully determined. Autophagy plays a crucial role in removing protein aggregates and damaged organelles to maintain intracellular homeostasis and function. The role of autophagy in HC-induced renal damage is unknown. We evaluated the expression of LC3/Atg8 as a marker of the autophagosome; p62/SQSTM1; polyubiquitin aggregates as markers of autophagy flux; Ambra1, PINK1, Parkin and Bnip3 as markers of mitophagy; 8-hydroxydeoxyguanosine (8-OHdG) as a marker of DNA oxidative damage; and p16 as a marker of organ aging by western blot and immunohistochemical staining in the kidneys of 24-month-old Fischer 344 rats. We also observed mitochondrial structure and autolysosomes by transmission electron microscopy. Expression of the autophagosome formation marker LC3/Atg8 and markers of mitochondrial autophagy (mitophagy) were markedly decreased in the kidneys of the HC group, and markedly increased in CR kidneys. p62/SQSTM1 and polyubiquitin aggregates increased in HC kidneys, and decreased in CR kidneys. Transmission electron microscopy demonstrated that HC kidneys showed severe abnormal mitochondrial morphology with fewer autolysosomes, while CR kidneys exhibited normal mitochondrial morphology with numerous autolysosomes. The level of 8-hydroxydeoxyguanosine was increased in HC kidneys and decreased in CR kidneys. Markers of aging, such as p16 and senescence-associated-galactosidase, were increased significantly in the HC group and decreased significantly in the CR group. The study firstly suggests that HC diet inhibits renal autophagy and aggravates renal oxidative damage and aging, while CR enhances renal autophagy and ameliorates oxidative damage and aging in the kidneys.

  5. Outcome of single pediatric deceased donor renal transplantation to adult kidney transplant recipients.

    PubMed

    Friedersdorff, Frank; Fuller, Tom Florian; Werthemann, Peter; Cash, Hannes

    2014-01-01

    In times of organ shortage more kidneys were transplanted in 'expanded criteria kidney' programs. This study examines the outcome of adult kidney recipients from pediatric donors. This single-center retrospective analysis evaluated eight adult patients who received a kidney from a deceased pediatric donor (age 5-17) between 06/2000 and 09/2011. The median donor age was 14 years (range 5-17). The median recipient age was 49 years (range 25-57). The median cold ischemia time was 13.3 h (range 4.3-20.1), while the median warm ischemia time was 53 min (range 42-60). The median follow-up was 35.8 months (range 7-142). Acute rejection was observed in 50.0% of cases. The median HLA mismatch was 2.0. The median 1-year creatinine level was 0.95 mg/dl, the uncensored 1-year graft survival was 75.0% and the 3-year graft survival 62.5%, respectively. No recipient died within the follow-up period. As severe surgical complications, one stenosis of the renal artery and one lymphocele needing surgical revision were observed. Renal transplantation of a deceased single pediatric donor to an adult recipient can be performed safely and shows a good outcome. Wherever feasible, single pediatric kidney transplantation can double the number of recipients over an 'en-bloc' transplantation. The price for a single pediatric kidney transplant may be a higher vascular complication rate and a higher rejection risk. Despite the higher risks, transplantation of a single pediatric donor kidney should be performed when accomplishable. 2013 S. Karger AG, Basel.

  6. Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

    PubMed

    Stratta, Robert J; Farney, Alan C; Orlando, Giuseppe; Farooq, Umar; Al-Shraideh, Yousef; Palanisamy, Amudha; Reeves-Daniel, Amber; Doares, William; Kaczmorski, Scott; Gautreaux, Michael D; Iskandar, Samy S; Hairston, Gloria; Brim, Elizabeth; Mangus, Margaret; El-Hennawy, Hany; Khan, Muhammad; Rogers, Jeffrey

    2016-04-01

    The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from

  7. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    PubMed

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  8. Gender differences in adenine-induced chronic kidney disease and cardiovascular complications in rats.

    PubMed

    Diwan, Vishal; Small, David; Kauter, Kate; Gobe, Glenda C; Brown, Lindsay

    2014-12-01

    Gender contributes to differences in incidence and progression of chronic kidney disease (CKD) and associated cardiovascular disease. To induce kidney damage in male and female Wistar rats (n = 12/group), a 0.25% adenine diet for 16 wk was used. Kidney function (blood urea nitrogen, plasma creatinine, proteinuria) and structure (glomerular damage, tubulointerstitial atrophy, fibrosis, inflammation); cardiovascular function (blood pressure, ventricular stiffness, vascular responses, echocardiography) and structure (cardiac fibrosis); plasma testosterone and estrogen concentrations; and protein expression for oxidative stress [heme oxygenase-1, inflammation (TNF-α), fibrosis (transforming growth factor-β), ERK1/2, and estrogen receptor-α (ER-α)] were compared in males and females. Adenine-fed females had less decline in kidney function than adenine-fed males, although kidney atrophy, inflammation, and fibrosis were similar. Plasma estrogen concentrations increased and plasma testosterone concentrations decreased in adenine-fed males, with smaller changes in females. CKD-associated molecular changes in kidneys were more pronounced in males than females except for expression of ER-α in the kidney, which was completely suppressed in adenine-fed males but unchanged in adenine-fed females. Both genders showed increased blood pressure, ventricular stiffness, and cardiac fibrosis with the adenine diet. Cardiovascular changes with adenine were similar in males and females, except males developed concentric, and females eccentric cardiac hypertrophy. In hearts from adenine-fed male and female rats, expression of ER-α and activation of the ERK1/2 pathway were increased, in part explaining changes in cardiac hypertrophy. In summary, adenine-induced kidney damage may be increased in males due to the suppression of ER-α.

  9. Expression of phosphorylated extracellular signal-regulated kinase in rat kidneys exposed to high +Gz

    PubMed Central

    Kim, Hyun-Soo; Kim, Youn Wha

    2012-01-01

    Exposure to high gravitational acceleration forces acting along the body axis from the head to the feet (+Gz) severely reduces blood flow to the visceral organs, including the kidneys. Extracellular signal-regulated kinase (ERK) figures predominantly in mediating kidney cell responses to a wide variety of stress-related stimuli. Though previous studies have shown the activation of ERK in some experimental models, the regulation of ERK associated with +Gz exposure has not yet been investigated. The aim of this study was to examine the effect of high +Gz exposure on ERK activation in the kidneys. Using a small animal centrifuge, eight male Sprague-Dawley rats were exposed to +10Gz or +13Gz three times for 3 minutes each. The bilateral kidneys were obtained from each rat, and the expression levels of phosphorylated ERK (p-ERK) were evaluated using immunohistochemistry. In the control group, the collecting duct epithelium displayed faint cytoplasmic staining with no nuclear staining of p-ERK. By contrast, rats exposed to +10Gz showed strong nuclear staining intensity for p-ERK. In the renal papilla, the epithelial cells of collecting ducts and thin segments of the loop of Henle exhibited strong nuclear immunoreactivity for p-ERK. Rats exposed to +13Gz also showed the same staining intensity and distribution of p-ERK expression as that of rats exposed to +10Gz. This study is the first to describe +Gz exposure-induced alteration in the expression of p-ERK in the kidneys. Our finding suggests that high +Gz exposure leads to the activation of ERK in the renal papilla. PMID:23198944

  10. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  11. Toxicity Evaluation of Graphene Oxide in Kidneys of Sprague-Dawley Rats

    PubMed Central

    Patlolla, Anita K.; Randolph, Jonathan; Kumari, S. Anitha; Tchounwou, Paul B.

    2016-01-01

    Recently, graphene and graphene-related materials have attracted a great deal of attention due their unique physical, chemical, and biocompatibility properties and to their applications in biotechnology and medicine. However, the reports on the potential toxicity of graphene oxide (GO) in biological systems are very few. The present study investigated the response of kidneys in male Sprague-Dawley rats following exposure to 0, 10, 20 and 40 mg/Kg GO for five days. The results showed that administration of GOs significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent manner in the kidneys compared with control group. Serum creatinine and blood urea nitrogen levels were also significantly increased in rats intoxicated with GO compared with the control group. There was a significant elevation in the levels of hydrogen peroxide and lipid hydro peroxide in GOs-treated rats compared to control animals. Histopathological evaluation showed significant morphological alterations of kidneys in GO-treated rats compared to controls. Taken together, the results of this study demonstrate that GO is nephrotoxic and its toxicity may be mediated through oxidative stress. In the present work, however, we only provided preliminary information on toxicity of GO in rats; further experimental verification and mechanistic elucidation are required before GO widely used for biomedical applications. PMID:27043588

  12. Toxicity Evaluation of Graphene Oxide in Kidneys of Sprague-Dawley Rats.

    PubMed

    Patlolla, Anita K; Randolph, Jonathan; Kumari, S Anitha; Tchounwou, Paul B

    2016-03-29

    Recently, graphene and graphene-related materials have attracted a great deal of attention due their unique physical, chemical, and biocompatibility properties and to their applications in biotechnology and medicine. However, the reports on the potential toxicity of graphene oxide (GO) in biological systems are very few. The present study investigated the response of kidneys in male Sprague-Dawley rats following exposure to 0, 10, 20 and 40 mg/Kg GO for five days. The results showed that administration of GOs significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent manner in the kidneys compared with control group. Serum creatinine and blood urea nitrogen levels were also significantly increased in rats intoxicated with GO compared with the control group. There was a significant elevation in the levels of hydrogen peroxide and lipid hydro peroxide in GOs-treated rats compared to control animals. Histopathological evaluation showed significant morphological alterations of kidneys in GO-treated rats compared to controls. Taken together, the results of this study demonstrate that GO is nephrotoxic and its toxicity may be mediated through oxidative stress. In the present work, however, we only provided preliminary information on toxicity of GO in rats; further experimental verification and mechanistic elucidation are required before GO widely used for biomedical applications.

  13. Ultrastructural changes and nestin expression accompanying compensatory renal growth after unilateral nephrectomy in adult rats

    PubMed Central

    Eladl, Mohamed Ahmed; M Elsaed, Wael; Atef, Hoda; El-Sherbiny, Mohamed

    2017-01-01

    Background Several renal disorders affect the glomerular podocytes. Compensatory structural and functional changes have been observed in animals that have undergone unilateral renal ablation. These changes occur as a pliant response to quench the increased functional demand to maintain homeostasis of fluid and solutes. Nestin is an intermediate filament protein present in the glomerular podocytes of the adult kidney and is linked with the maintenance of its foot process structure. Structural changes in the podocytes ultimately restructure the filtration barrier. Very few studies related to the ultrastructural and histopathologic changes of the podocytes are documented. The present study aimed to assess the histopathologic changes at the ultrastructural level in the adapted kidney at different time intervals following unilateral renal ablation in adult rats and its relation with nestin. Methods Forty-eight rats were divided into four groups (n=12 in each group). The animals of Group A were control naïve rats, while the group B, group C and group D animals underwent left unilateral nephrectomy and the remaining right kidney was removed on days 10, 20 and 30, respectively. Each group included four sham-operated rats, which were sacrificed at the same time as the naïve rats. Each nephrectomized sample was weighed and its sections were subjected to hematoxylin and eosin examination, transmission electron microscopic study as well as immunostaining using the intermediate filament protein nestin. Results No difference was found between the kidney sections from the control group and the sham-operated groups. A significant increase in the weight of the right kidneys was noted in groups B, C and D (P<0.001). The ultrastructural adaptive changes seen in the glomeruli of group B were subsequently reduced in groups C and D. This finding corresponded to a similar pattern of nestin expression in the podocytes, which showed significant increase in group B followed by reduced

  14. Economic impact of kidney stones in white male adults.

    PubMed

    Shuster, J; Scheaffer, R L

    1984-10-01

    A large survey of patients hospitalized for kidney stones in the Carolinas and the Rocky Mountain states yielded information that can be translated into conservative estimates of cost of this disease. Hospital costs were estimated by considering number of surgeries, the approximate cost of various types of surgery, number of days hospitalized, and room rates. Work force costs were estimated from information on work days lost and income categories. Estimated recurrence rates for this disease are used to approximate the total cost, due to stones, for the next year for a current stone case. Each incident of stone disease costs, on the average, approximately $2,000, exclusive of recurrences. Hospital stays average four to five days. The average annual cost of recurrence for a current stone case is conservatively estimated to be in the $300 to $400 range. A conservative projection of these costs to the entire national population of white males in the age range of eighteen to sixty years yields an annual cost due to kidney stones approaching $315,000,000.

  15. Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny.

    PubMed

    Garoui, El Mouldi; Troudi, Afef; Fetoui, Hamadi; Soudani, Nejla; Boudawara, Tahia; Zeghal, Najiba

    2012-11-01

    The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl(2) in drinking water; group 3 received 350 ppm CoCl(2) in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity. Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period. Copyright © 2011 Elsevier GmbH. All rights reserved.

  16. Gene expression profiling of kidneys from Sprague-Dawley rats following 12-week inhalation exposure to silver nanoparticles.

    PubMed

    Dong, Mi Sook; Choi, Ji-Yoon; Sung, Jae Hyuck; Kim, Jin Sik; Song, Kyung Seuk; Ryu, Hyun Ryol; Lee, Ji Hyun; Bang, In Seok; An, Kangho; Park, Hyun Min; Song, Nam Woong; Yu, Il Je

    2013-07-01

    The specific properties of silver nanoparticles (AgNPs), such as antimicrobial activity and electrical conductivity, allow them to be used in many fields. However, their expanding application is also raising health, environmental and safety concerns. Previous in vivo AgNP toxicity studies have indicated a gender-different accumulation of silver in the kidneys, with 2-3 times more silver in female kidneys compared to male kidneys. However, no other studies have further addressed this gender difference. Accordingly, the current study investigated the gender-dependent effect of AgNPs on the kidney gene level based on toxicogenomic studies of kidneys obtained from rats exposed to AgNPs via inhalation for 12 weeks. When compared with the fresh air control, the silver nanoparticle-exposed kidneys included 104 genes with a more than 1.3-fold expression increase. For the male rat kidneys exposed to a low or high dose of silver nanoparticles, 96 genes exhibited expression changes, where six genes changed with both the low and high dose; four increased and two decreased. Meanwhile, for the female rat kidneys exposed to a low or high dose of silver nanoparticles, 66 genes exhibited expression changes, where 11 genes changed with both the low and high dose; nine increased and two decreased. Gender-dependent gene expression changes of more than 2-fold were linked to 163 genes, with 79 genes in the male kidneys and 84 genes in the female kidneys, plus gender-dependent gene expression changes of more than 5-fold were linked to 21 genes. However, no genes involved in apoptosis or the cell cycle were activated by the 12-week silver nanoparticle inhalation exposure. Overall, the male rat kidneys showed a higher expression of genes involved in xenobiotic metabolism, while the female rat kidneys showed a higher expression of genes involved in extracellular signaling.

  17. The diabetic rat kidney mediates inosituria and selective urinary partitioning of D-chiro-inositol.

    PubMed

    Chang, Hao-Han; Choong, Bernard; Phillips, Anthony R J; Loomes, Kerry M

    2015-01-01

    Diabetic nephropathy is a serious complication of diabetes mellitus with a pressing need for effective metabolic markers to detect renal impairment. Of potential significance are the inositol compounds, myo-inositol (MI), and the less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at increased levels in the urine in diabetes mellitus, a phenomenon known as inosituria. There is also a selective urinary excretion of DCI compared to MI. As the biological origins of altered inositol metabolism in diabetes mellitus are unknown, the aim of this study was to determine whether the diabetic kidney was directly responsible. Kidneys isolated from four-week streptozotocin-induced diabetic rats were characterized by a 3-fold reduction in glomerular filtration rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed quantities of MI (50 µM) and DCI (5 µM) under normoglycemic conditions (5 mM glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary excretion of DCI was increased by 4-fold. Perfusion conditions replicating hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in DCI urinary excretion compared to MI in diabetic kidneys that was independent of glucose ambience. This increased urinary excretion of DCI and MI in diabetic kidneys occurred despite increased renal expression of the inositol transporters, sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings show that the diabetic kidney primarily mediates inosituria and altered urinary partitioning of MI and DCI. Urinary inositol levels might therefore serve as an indicator of impaired renal function in diabetes mellitus with wider implications for monitoring chronic kidney disease.

  18. Genetic susceptibility to hypertension-induced renal damage in the rat. Evidence based on kidney-specific genome transfer.

    PubMed Central

    Churchill, P C; Churchill, M C; Bidani, A K; Griffin, K A; Picken, M; Pravenec, M; Kren, V; St Lezin, E; Wang, J M; Wang, N; Kurtz, T W

    1997-01-01

    To test the hypothesis that genetic factors can determine susceptibility to hypertension-induced renal damage, we derived an experimental animal model in which two genetically different yet histocompatible kidneys are chronically and simultaneously exposed to the same blood pressure profile and metabolic environment within the same host. Kidneys from normotensive Brown Norway rats were transplanted into unilaterally nephrectomized spontaneously hypertensive rats (SHR-RT1.N strain) that harbor the major histocompatibility complex of the Brown Norway strain. 25 d after the induction of severe hypertension with deoxycorticosterone acetate and salt, proteinuria, impaired glomerular filtration rate, and extensive vascular and glomerular injury were observed in the Brown Norway donor kidneys, but not in the SHR-RT1.N kidneys. Control experiments demonstrated that the strain differences in kidney damage could not be attributed to effects of transplantation-induced renal injury, immunologic rejection phenomena, or preexisting strain differences in blood pressure. These studies (a) demonstrate that the kidney of the normotensive Brown Norway rat is inherently much more susceptible to hypertension-induced damage than is the kidney of the spontaneously hypertensive rat, and (b) establish the feasibility of using organ-specific genome transplants to map genes expressed in the kidney that determine susceptibility to hypertension-induced renal injury in the rat. PMID:9294102

  19. Protective effects of exogenous β-hydroxybutyrate on paraquat toxicity in rat kidney

    SciTech Connect

    Wei, Teng; Tian, Wulin; Liu, Fangning; Xie, Guanghong

    2014-05-16

    Highlights: • β-Hydroxybutyrate inhibits paraquat-induced toxicity in rat kidney. • β-Hydroxybutyrate inhibits lipid peroxidation and caspase-mediated apoptosis. • β-Hydroxybutyrate increases the activities of SOD and CAT. • The study describes a novel finding for the renoprotective ability of β-hydroxybutyrate. - Abstract: In this study, we demonstrated the protective effects of β-hydroxybutyrate (β-HB) against paraquat (PQ)-induced kidney injury and elucidated the underlying molecular mechanisms. By histological examination and renal dysfunction specific markers (serum BUN and creatinine) assay, β-HB could protect the PQ-induced kidney injury in rat. PQ-induced kidney injury is associated with oxidative stress, which was measured by increased lipid peroxidation (MDA) and decreased intracellular anti-oxidative abilities (SOD, CAT and GSH). β-HB pretreatment significantly attenuated that. Caspase-mediated apoptosis pathway contributed importantly to PQ toxicity, as revealed by the activation of caspase-9/-3, cleavage of PARP, and regulation of Bcl-2 and Bax, which were also effectively blocked by β-HB. Moreover, treatment of PQ strongly decreased the nuclear Nrf2 levels. However, pre-treatment with β-HB effectively suppressed this action of PQ. This may imply the important role of β-HB on Nrf2 pathway. Taken together, this study provides a novel finding that β-HB has a renoprotective ability against paraquat-induced kidney injury.

  20. Renal primordia activate kidney regenerative events in a rat model of progressive renal disease.

    PubMed

    Imberti, Barbara; Corna, Daniela; Rizzo, Paola; Xinaris, Christodoulos; Abbate, Mauro; Longaretti, Lorena; Cassis, Paola; Benedetti, Valentina; Benigni, Ariela; Zoja, Carlamaria; Remuzzi, Giuseppe; Morigi, Marina

    2015-01-01

    New intervention tools for severely damaged kidneys are in great demand to provide patients with a valid alternative to whole organ replacement. For repairing or replacing injured tissues, emerging approaches focus on using stem and progenitor cells. Embryonic kidneys represent an interesting option because, when transplanted to sites such as the renal capsule of healthy animals, they originate new renal structures. Here, we studied whether metanephroi possess developmental capacity when transplanted under the kidney capsule of MWF male rats, a model of spontaneous nephropathy. We found that six weeks post-transplantation, renal primordia developed glomeruli and tubuli able to filter blood and to produce urine in cyst-like structures. Newly developed metanephroi were able to initiate a regenerative-like process in host renal tissues adjacent to the graft in MWF male rats as indicated by an increase in cell proliferation and vascular density, accompanied by mRNA and protein upregulation of VEGF, FGF2, HGF, IGF-1 and Pax-2. The expression of SMP30 and NCAM was induced in tubular cells. Oxidative stress and apoptosis markedly decreased. Our study shows that embryonic kidneys generate functional nephrons when transplanted into animals with severe renal disease and at the same time activate events at least partly mimicking those observed in kidney tissues during renal regeneration.

  1. A rat model of chronic kidney disease-mineral bone disorder.

    PubMed

    Moe, Sharon M; Chen, Neal X; Seifert, Mark F; Sinders, Rachel M; Duan, Dana; Chen, Xianming; Liang, Yun; Radcliff, J Scott; White, Kenneth E; Gattone, Vincent H

    2009-01-01

    Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) is a newly defined syndrome encompassing patients with chronic kidney disease that have a triad of biochemical alterations in calcium, phosphorus and parathyroid hormone, vascular calcification, and bone abnormalities. Here we describe a novel Cy/+ rat model of slowly progressive kidney disease spontaneously developing the three components of CKD-MBD when fed a normal phosphorus diet. Since the renal disorder progressed 'naturally' we studied the effect of dietary manipulation during the course of the disease. Animals with early, but established, chronic kidney disease were fed a casein-based or a grain-based protein diet both of which had equivalent total phosphorus contents. The two different sources of dietary protein had profound effects on the progression of CKD-MBD, likely due to differences in intestinal bioavailability of phosphorus. Although both dietary treatments resulted in the same serum phosphorous levels, the casein-fed animals had increased urinary phosphorus excretion and elevated serum FGF23 compared to the grain-fed rats. This model should help identify early changes in the course of chronic kidney disease that may lead to CKD-MBD.

  2. Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models

    PubMed Central

    Li, Shunan; Abedin, Md. Joynal; Noppakun, Kajohnsak; Wang, Lawrence; Kaur, Tarundeep; Najafian, Behzad; Rodrigues, Cecília M. P.

    2012-01-01

    Background Acute kidney injury (AKI) has grave short- and long-term consequences. Often the onset of AKI is predictable, such as following surgery that compromises blood flow to the kidney. Even in such situations, present therapies cannot prevent AKI. As apoptosis is a major form of cell death following AKI, we determined the efficacy and mechanisms of action of tauroursodeoxycholic acid (TUDCA), a molecule with potent anti-apoptotic and pro-survival properties, in prevention of AKI in rat and cell culture models. TUDCA is particularly attractive from a translational standpoint, as it has a proven safety record in animals and humans. Methodology/Principal Findings We chose an ischemia-reperfusion model in rats to simulate AKI in native kidneys, and a human kidney cell culture model to simulate AKI associated with cryopreservation in transplanted kidneys. TUDCA significantly ameliorated AKI in the test models due to inhibition of the mitochondrial pathway of apoptosis and upregulation of survival pathways. Conclusions This study sets the stage for testing TUDCA in future clinical trials for prevention of AKI, an area that needs urgent attention due to lack of effective therapies. PMID:23152827

  3. Ameliorative effects of pine bark extract on cisplatin-induced acute kidney injury in rats.

    PubMed

    Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Shin, Na-Rae; Shin, In-Sik; Kim, Yun-Bae; Kim, Jong-Choon

    2017-11-01

    This study investigated the dose-response effects of pine bark extract (PBE, pycnogenol(®)) on oxidative stress-mediated apoptotic changes induced by cisplatin (Csp) in rats. The ameliorating potential of PBE was evaluated after orally administering PBE at doses of 10 or 20 mg/kg for 10 days. Acute kidney injury was induced by a single intraperitoneal injection of Csp at 7 mg/kg on test day 5. Csp treatment caused acute kidney injury manifested by elevated levels of serum blood urea nitrogen (BUN) and creatinine (CRE) with corresponding histopathological changes, including degeneration of tubular epithelial cells, hyaline casts in the tubular lumen, and inflammatory cell infiltration (interstitial nephritis). Csp also induced significant apoptotic changes in renal tubular cells. In addition, Csp treatment induced high levels of oxidative stress, as evidenced by an increased level of malondialdehyde, depletion of the reduced glutathione (GSH) content, and decreased activities of glutathione S-transferase, superoxide dismutase, and catalase in kidney tissues. On the contrary, PBE treatment lowered BUN and CRE levels and effectively attenuated histopathological alterations and apoptotic changes induced by Csp. Additionally, treatment with PBE suppressed lipid peroxidation, prevented depletion of GSH, and enhanced activities of the antioxidant enzymes in kidney tissue. These results indicate that PBE has a cytoprotective effect against oxidative stress-mediated apoptotic changes caused by Csp in the rat kidney, which may be attributed to both increase of antioxidant enzyme activities and inhibition of lipid peroxidation.

  4. Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury.

    PubMed

    Villa, Luca; Buono, Roberta; Ferrandi, Mara; Molinari, Isabella; Benigni, Fabio; Bettiga, Arianna; Colciago, Giorgia; Ikehata, Masami; Messaggio, Elisabetta; Rastaldi, Maria Pia; Montorsi, Francesco; Salonia, Andrea; Manunta, Paolo

    2016-10-14

    Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2-3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.

  5. Spontaneous Age-related Lesions of the Kidney Fornices in Sprague-Dawley Rats.

    PubMed

    Tomonari, Yuki; Kurotaki, Tetsuro; Sato, Junko; Doi, Takuya; Kokoshima, Hiroko; Kanno, Takeshi; Tsuchitani, Minoru; Seely, John Curtis

    2016-02-01

    The upper portion of the rat kidney pelvis has specialized anatomic structures referred to as fornices. Fornices have a role in urine concentration. Spontaneous lesions including mineralization, epithelial hyperplasia, and inflammatory cell infiltration may occur in the area of the fornices. However, little information regarding specific historical control data or the spontaneous development of these findings in male and female fornices is known. Understanding spontaneous age-related lesions in the area of the fornices versus other portions of the kidney pelvis may be relevant in the identification of test article-induced changes. A retrospective study was conducted of male and female Sprague-Dawley rat kidney fornices over several time points to determine the incidence and severity of mineralization, epithelial hyperplasia, and inflammatory cell infiltration. Based on this investigation, these lesions appeared to increase over time and, in general, occurred earlier and with a greater incidence in females. Regarding those chemicals that may result in lesions of the kidney pelvis, it may be important for pathologists to separately diagnose lesions of the fornices from other portions of the kidney pelvis to help differentiate between any spontaneous age-related and induced changes.

  6. Renal Primordia Activate Kidney Regenerative Events in a Rat Model of Progressive Renal Disease

    PubMed Central

    Imberti, Barbara; Corna, Daniela; Rizzo, Paola; Xinaris, Christodoulos; Abbate, Mauro; Longaretti, Lorena; Cassis, Paola; Benedetti, Valentina; Benigni, Ariela; Zoja, Carlamaria; Remuzzi, Giuseppe; Morigi, Marina

    2015-01-01

    New intervention tools for severely damaged kidneys are in great demand to provide patients with a valid alternative to whole organ replacement. For repairing or replacing injured tissues, emerging approaches focus on using stem and progenitor cells. Embryonic kidneys represent an interesting option because, when transplanted to sites such as the renal capsule of healthy animals, they originate new renal structures. Here, we studied whether metanephroi possess developmental capacity when transplanted under the kidney capsule of MWF male rats, a model of spontaneous nephropathy. We found that six weeks post-transplantation, renal primordia developed glomeruli and tubuli able to filter blood and to produce urine in cyst-like structures. Newly developed metanephroi were able to initiate a regenerative-like process in host renal tissues adjacent to the graft in MWF male rats as indicated by an increase in cell proliferation and vascular density, accompanied by mRNA and protein upregulation of VEGF, FGF2, HGF, IGF-1 and Pax-2. The expression of SMP30 and NCAM was induced in tubular cells. Oxidative stress and apoptosis markedly decreased. Our study shows that embryonic kidneys generate functional nephrons when transplanted into animals with severe renal disease and at the same time activate events at least partly mimicking those observed in kidney tissues during renal regeneration. PMID:25811887

  7. Life cycle analysis of kidney gene expression in male F344 rats.

    PubMed

    Kwekel, Joshua C; Desai, Varsha G; Moland, Carrie L; Vijay, Vikrant; Fuscoe, James C

    2013-01-01

    Age is a predisposing condition for susceptibility to chronic kidney disease and progression as well as acute kidney injury that may arise due to the adverse effects of some drugs. Age-related differences in kidney biology, therefore, are a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of genes expressed in the kidney at various life cycle stages will impact susceptibility to adverse drug reactions. Therefore, establishing changes in baseline expression data between these life stages is the first and necessary step in evaluating this hypothesis. Untreated male F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age. Kidneys were collected for histology and gene expression analysis. Agilent whole-genome rat microarrays were used to query global expression profiles. An ANOVA (p<0.01) coupled with a fold-change>1.5 in relative mRNA expression, was used to identify 3,724 unique differentially expressed genes (DEGs). Principal component analyses of these DEGs revealed three major divisions in life-cycle renal gene expression. K-means cluster analysis identified several groups of genes that shared age-specific patterns of expression. Pathway analysis of these gene groups revealed age-specific gene networks and functions related to renal function and aging, including extracellular matrix turnover, immune cell response, and renal tubular injury. Large age-related changes in expression were also demonstrated for the genes that code for qualified renal injury biomarkers KIM-1, Clu, and Tff3. These results suggest specific groups of genes that may underlie age-specific susceptibilities to adverse drug reactions and disease. This analysis of the basal gene expression patterns of renal genes throughout the life cycle of the rat will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease.

  8. Decreased ornithine decarboxylase activity in the kidneys of Dahl salt-sensitive rats.

    PubMed

    Hayashi, Takeshi; Tsujino, Takeshi; Iwata, Sachiyo; Nonaka, Hidemi; Emoto, Noriaki; Yano, Yoshihisa; Otani, Shuzo; Hayashi, Yoshitake; Itoh, Hiroshi; Yokoyama, Mitsuhiro

    2002-09-01

    To assess the roles of polyamines (putrescine, spermidine, and spermine) and ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, in the development of salt-sensitive hypertension, we evaluated activity and expression of ODC, urinary polyamine excretion, and antizyme (endogenous ODC inhibitor protein) expression in Dahl salt-sensitive (SS) and salt-resistant (SR) rats after they were fed on a low (0.3%) or high (4%) salt diet for 4 weeks. We also examined the effects of spermidine and difluoromethylornithine (DFMO: a specific inhibitor of ODC) on the systolic blood pressure and ODC protein expression in SS rats fed a high salt diet. Renal ODC activity and urinary polyamine excretion in SS rats were lower than those in SR rats after 4 weeks treatment with a low or high salt diet. The renal ODC protein expression of SS rats was paradoxically increased as compared to the SR group. A high salt diet did not alter ODC activity but increased ODC protein only in SS rats. ODC mRNA and antizyme protein expressions were not significantly different among the four groups. Spermidine supplementation attenuated and DFMO exaggerated hypertension in SS rats fed a high salt diet. Spermidine down-regulated and DFMO up-regulated renal ODC protein in SS rats on a high salt diet. ODC activity was decreased but protein was paradoxically increased in kidneys of SS rats. ODC protein was suggested to increase in compensation for the inhibition of its activity. Impaired ODC activity and polyamine production in the kidney may exaggerate salt-sensitive hypertension in SS rats.

  9. A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8

    PubMed Central

    2012-01-01

    Background Nephronophthisis (NPHP) as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK) rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a)- related kinase 8 ( Nek8) gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1)-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins. PMID:22899815

  10. En bloc kidney transplantation from pediatric cadaveric donors to adult recipients.

    PubMed

    Mahdavi, Reza; Arab, Davood; Taghavi, Rahim; Gholamrezaie, Hamid Reza; Yazdani, Mohammad; Simforoosh, Nasser; Tabibi, Ali

    2006-01-01

    The shortage of cadaveric donors for kidney transplantation has led to the expansion of the criteria used for donor selection, such as the use of pediatric cadaveric donors. In this study we reviewed our results of en bloc kidney transplantation of pediatric cadaveric donors to adults. From May 2001 to May 2005, 245 cadaveric kidney transplants have been performed in our hospitals. Seven of these were en bloc kidney transplantations in adult recipients from marginal pediatric donors (age < 5 years, donor weight < 15 kg, high creatinine clearance, or kidney length < 8 cm). We reviewed their records. Follow-up (range, 3 to 24 months) included ultrasonography, dimercaptosuccinic acid renal scintigraphy, and magnetic resonance imaging. Serum levels of creatinine ranged between 0.8 m/dL to 1.9 mg/dL during the follow-up period. One patient died of myocardial infarction 3 months postoperatively. One-year graft and patient survivals were both 85.7%. Complications included acute tubular necrosis in 1 patient (managed by conservative therapy and dialysis for 2 weeks), renal vein thrombosis in 1 (treated by anticoagulation), and subcutaneous hematoma in 1. There were no urologic complications. Median size of the grafts was 7.2 cm preoperatively that reached 9.6 cm, 3 months postoperatively (P = .018). Twelve months following operation, the median size of the grafts reached 11 cm (P = .045). En bloc pediatric kidney transplantation is a safe and suitable alternative for adult recipients. One-year graft and patient survivals are acceptable and complication rate is low.

  11. Constitutive renal Rel/nuclear factor-κB expression in Lewis polycystic kidney disease rats

    PubMed Central

    Ta, Michelle H T; Schwensen, Kristina G; Liuwantara, David; Huso, David L; Watnick, Terry; Rangan, Gopala K

    2016-01-01

    AIM: To determine the temporal expression and pattern of Rel/nuclear factor (NF)-κB proteins in renal tissue in polycystic kidney disease (PKD). METHODS: The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofluorescence and immunoblot analysis in Lewis polycystic kidney rats (LPK, a genetic ortholog of human nephronopthsis-9) from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes (TNFα and CCL2) were determined. NF-κB was also histologically assessed in human PKD tissue. RESULTS: Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation (peaking at weeks 3 and 10 respectively), and progressive interstitial fibrosis (with α smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards). Rel/NF-κB proteins (phosphorylated-p105, p65, p50, c-Rel and RelB) were expressed in cystic epithelial cells (CECs) of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBα protein levels, and TNFα and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identified in the CECs of LPK and human polycystic kidneys. CONCLUSION: Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases. PMID:27458563

  12. Constitutive renal Rel/nuclear factor-κB expression in Lewis polycystic kidney disease rats.

    PubMed

    Ta, Michelle H T; Schwensen, Kristina G; Liuwantara, David; Huso, David L; Watnick, Terry; Rangan, Gopala K

    2016-07-06

    To determine the temporal expression and pattern of Rel/nuclear factor (NF)-κB proteins in renal tissue in polycystic kidney disease (PKD). The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofluorescence and immunoblot analysis in Lewis polycystic kidney rats (LPK, a genetic ortholog of human nephronopthsis-9) from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes (TNFα and CCL2) were determined. NF-κB was also histologically assessed in human PKD tissue. Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation (peaking at weeks 3 and 10 respectively), and progressive interstitial fibrosis (with α smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards). Rel/NF-κB proteins (phosphorylated-p105, p65, p50, c-Rel and RelB) were expressed in cystic epithelial cells (CECs) of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBα protein levels, and TNFα and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identified in the CECs of LPK and human polycystic kidneys. Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.

  13. Hemodynamic and neural responses to renal denervation of the nerve to the clipped kidney by cryoablation in two-kidney, one-clip hypertensive rats.

    PubMed

    Rossi, Noreen F; Pajewski, Russell; Chen, Haiping; Littrup, Peter J; Maliszewska-Scislo, Maria

    2016-01-15

    Renal artery stenosis is increasing in prevalence. Angioplasty plus stenting has not proven to be better than medical management. There has been a reluctance to use available denervation methodologies in this condition. We studied conscious, chronically instrumented, two-kidney, one-clip (2K-1C) Goldblatt rats, a model of renovascular hypertension, to test the hypothesis that renal denervation by cryoablation (cryo-DNX) of the renal nerve to the clipped kidney decreases mean arterial pressure (MAP), plasma and tissue ANG II, and contralateral renal sympathetic nerve activity (RSNA). Five-week-old male Sprague-Dawley rats underwent sham (ShC) or right renal artery clipping (2K-1C), placement of telemetry transmitters, and pair-feeding with a 0.4% NaCl diet. After 6 wk, rats were randomly assigned to cryo-DNX or sham cryotreatment (sham DNX) of the renal nerve to the clipped kidney. MAP was elevated in 2K-1C and decreased significantly in both ShC cryo-DNX and 2K-1C cryo-DNX. Tissue norepinephrine was ∼85% lower in cryo-DNX kidneys. Plasma ANG II was higher in 2K-1C sham DNX but not in 2K-1C cryo-DNX vs ShC. Renal tissue ANG II in the clipped kidney decreased after cryo-DNX. Baseline integrated RSNA of the unclipped kidney was threefold higher in 2K-1C versus ShC and decreased in 2K-1C cryo-DNX to values similar to ShC. Maximum reflex response of RSNA to baroreceptor unloading in 2K-1C was lower after cryo-DNX. Thus, denervation by cryoablation of the renal nerve to the clipped kidney decreases not only MAP but also plasma and renal tissue ANG II levels and RSNA to the contralateral kidney in conscious, freely moving 2K-1C rats.

  14. Increase of peripheral type benzodiazepine binding sites in kidney and olfactory bulb in acutely stressed rats.

    PubMed

    Novas, M L; Medina, J H; Calvo, D; De Robertis, E

    1987-03-17

    Fifteen minutes after the initiation of swimming stress in the rat we observed a 50% increase in the number of [3H]RO 5-4864 binding sites in kidney and a 37% increase in the olfactory bulb, without change in affinity. The binding in heart and cerebral cortex remained unchanged after the stress. These results are discussed in relation to previous work on both the action of an acute stress in central benzodiazepine receptors and the possible modulation of peripheral benzodiazepine receptors of the kidney by adrenocortical hormones.

  15. Sexual dimorphism in thyroid function and type 1 iodothyronine deiodinase activity in pre-pubertal and adult rats.

    PubMed

    Marassi, Michelle P; Fortunato, Rodrigo S; da Silva, Alba C Matos; Pereira, Valmara S; Carvalho, Denise P; Rosenthal, Doris; da Costa, Vânia M Corrêa

    2007-01-01

    Iodothyronine deiodinase activities are regulated by sex steroids; however, the mechanisms underlying the reported sexual dimorphism are poorly defined. In the present report, we aimed to investigate whether type 1 deiodinase (D1) sexual dimorphism exists early in sexual development by studying pre-pubertal male (Pm) and female (Pf) rats, as well as adult controls (C) and gonadectomized male and females rats. Adult male Wistar rats were studied 21 days after orchiectomy (Tex), and adult females were studied 21 days after ovariectomy (Ovx), and after estradiol benzoate (Eb) replacement. Serum total triiodothyronine (T3) was higher in pre-pubertal (P) rats than in the matching adults, with no difference between genders, although in adult males T3 was significantly lower than in females. There were no sex or age differences in serum total T4. Serum TSH in pre-pubertal (P) rats was within the adult female range, and both were significantly lower than in adult males. D1 activity in liver was greater in Pm than in Pf. In adult females, liver D1 activity was lower, while in adult males it was higher than in P rats. The same pattern of D1 activity was found in kidney. In thyroid and pituitary, D1 activity was similar in Pm, Pf, and adult females, which were all significantly lower than in the adult male. There were no differences in serum T3 and T4 between C and Tex males, but serum TSH was significantly decreased in Tex rats. Hepatic and renal D1 activities were lower in Tex than in C, but no changes were detected in thyroid and pituitary. In Ovx females, T3 was significantly lower than in the C group. Serum T4 was significantly decreased by estradiol replacement therapy in Ovx rats, in both doses used, whereas TSH was unchanged. Eb replacement increased liver and thyroid D1 activity, but in the kidney, only the highest estradiol dose promoted a significant D1 increase. In conclusion, in males, hepatic and renal D1 activity appears to be significantly influenced by

  16. Opioid binding sites in the guinea pig and rat kidney: Radioligand homogenate binding and autoradiography

    SciTech Connect

    Dissanayake, V.U.; Hughes, J.; Hunter, J.C. )

    1991-07-01

    The specific binding of the selective {mu}-, {delta}-, and {kappa}-opioid ligands (3H)(D-Ala2,MePhe4,Gly-ol5)enkephalin ((3H) DAGOL), (3H)(D-Pen2,D-Pen5)enkephalin ((3H)DPDPE), and (3H)U69593, respectively, to crude membranes of the guinea pig and rat whole kidney, kidney cortex, and kidney medulla was investigated. In addition, the distribution of specific 3H-opioid binding sites in the guinea pig and rat kidney was visualized by autoradiography. Homogenate binding and autoradiography demonstrated the absence of {mu}- and {kappa}-opioid binding sites in the guinea pig kidney. No opioid binding sites were demonstrable in the rat kidney. In the guinea pig whole kidney, cortex, and medulla, saturation studies demonstrated that (3H)DPDPE bound with high affinity (KD = 2.6-3.5 nM) to an apparently homogeneous population of binding sites (Bmax = 8.4-30 fmol/mg of protein). Competition studies using several opioid compounds confirmed the nature of the {delta}-opioid binding site. Autoradiography experiments demonstrated that specific (3H)DPDPE binding sites were distributed radially in regions of the inner and outer medulla and at the corticomedullary junction of the guinea pig kidney. Computer-assisted image analysis of saturation data yielded KD values (4.5-5.0 nM) that were in good agreement with those obtained from the homogenate binding studies. Further investigation of the {delta}-opioid binding site in medulla homogenates, using agonist ((3H)DPDPE) and antagonist ((3H)diprenorphine) binding in the presence of Na+, Mg2+, and nucleotides, suggested that the {delta}-opioid site is linked to a second messenger system via a GTP-binding protein. Further studies are required to establish the precise localization of the {delta} binding site in the guinea pig kidney and to determine the nature of the second messenger linked to the GTP-binding protein in the medulla.

  17. Elevated BSC-1 and ROMK expression in Dahl salt-sensitive rat kidneys.

    PubMed

    Hoagland, Kimberly M; Flasch, Averia K; Dahly-Vernon, Annette J; dos Santos, Elisabete Alcantara; Knepper, Mark A; Roman, Richard J

    2004-04-01

    This study compared the expression of enzymes and transport and channel proteins involved in the regulation of sodium reabsorption in the kidney of Dahl salt-sensitive (DS) and salt-resistant Brown-Norway (BN) and consomic rats (SS.BN13), in which chromosome 13 from the BN rat has been introgressed into the DS genetic background. The expression of the Na+/K+/2Cl- (BSC-1) cotransporter, Na+/H+ exchanger (NHE3), and Na+-K+-ATPase proteins were similar in the renal cortex of DS, BN, and SS.BN13 rats fed either a low-salt (0.1% NaCl) or a high-salt (8% NaCl) diet. The expression of the BSC-1 and the renal outer medullary K+ channel (ROMK) were higher, whereas the expression of the cytochrome P4504A proteins responsible for the formation of 20-hydroxyeicosatetraenoic (20-HETE) was lower in the outer medulla of the kidney of DS than in BN or SS.BN13 rats fed either a low-salt or a high-salt diet. In addition, the renal formation and excretion of 20-HETE was lower in DS than in BN and SS.BN13 rats. These results suggest that overexpression of ROMK and BSC-1 in the thick ascending limb combined with a deficiency in renal formation of 20-HETE may predispose Dahl S rats fed a high-salt diet to Na+ retention and hypertension.

  18. The kidneys play a central role in the clearance of rhGH in rats.

    PubMed

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads; Fels, Johannes Josef; Lykkesfeldt, Jens; Agersø, Henrik

    2016-04-30

    The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rhGH in non-anesthetized rats, anesthetized rats and in nephrectomized anesthetized rats. Clearance in non-anesthetized rats was 290 ml/h/kg. This was reduced to 185 ml/h/kg by anesthesia and further reduced to 18 ml/h/kg by nephrectomy. As nephrectomy was able to reduce clearance with 90%, we conclude that renal clearance plays a pivotal role in the elimination of rhGH in rats.

  19. Rat Kidney Cancers Determined by Dietary Ochratoxin A in the First Year of Life

    PubMed Central

    2016-01-01

    An experiment to explore renal carcinogenic efficacy of male rat exposure to dietary ochratoxin A (OTA) only in the first year of life has been made in comparison to lifetime exposure. Ten months exposure to OTA at 300 µg/kg b.w. was sufficient to cause high incidence of tumours which became apparent clinically after a latency of up to a year. As a putative model for human kidney cancer, the study shows a silent organ-specific carcinogenic effect through protracted exposure up to middle age and focused probably on very few nephrons. So far, tumourigenesis has not been recognised until in the last quarter of natural rat life, but for OTA, rat renal carcinogenesis requires both long exposure and only during the first year of normal longevity. The present findings offer an experimental framework within which systematic histopathology during tumourigenesis might show whether findings of mechanistic studies in key focal neoplasms can reasonably be applied to OTA as a putative renal carcinogen for idiopathic kidney cancer in humans. Already, the rat tumours mimic those occurring spontaneously in the Eker rat, and there is disparity between the large necessary OTA exposure in the rat and the trace amounts of OTA consumed by humans. In all such complex considerations it is important to adhere rigorously to established principles of disease epidemiology. PMID:28326281

  20. Increased Expression of p-Akt correlates with Chronic Allograft Nephropathy in a Rat Kidney Model.

    PubMed

    Zhou, Li-Na; Wang, Ning; Dong, Yang; Zhang, Yiqin; Zou, Hequn; Li, Qingqin; Shi, Yangling; Chen, Ling; Zhou, Wenying; Han, Conghui; Wang, Yuxin

    2015-04-01

    Chronic allograft nephropathy (CAN) is the most common cause of chronic graft dysfunction leading to graft failure, our study investigates the expression and significance of p-Akt in the pathogenesis of CAN in rats. Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. Phosphorate Akt (p-Akt) protein expression was determined by Western blot and immunohistological assays. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts got severe interstitial infiltration of mononuclear cells at week 4 and week 8, but it was degraded as the time went on after week 16. Allografts markedly presented with severe interstitial fibrosis (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. p-Akt expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and IF. It was concluded that p-Akt overexpression might be the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and IF and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.

  1. Antihypertensive medications and the risk of kidney stones in older adults: a retrospective cohort study.

    PubMed

    Alexander, R Todd; McArthur, Eric; Jandoc, Racquel; Welk, Blayne; Hayward, Jade S; Jain, Arsh K; Braam, Branko; Flockerzi, Veit; Garg, Amit X; Quinn, Robert Ross

    2017-09-01

    Antihypertensives are widely prescribed and could influence kidney stone risk by altering urinary calcium excretion. However, the impact of different classes of antihypertensives on kidney stone risk is unknown. To assess this impact, we conducted a retrospective, population-based cohort study using linked health administrative databases. Individuals aged >65 years who initiated one of the four antihypertensive classes (that is, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), beta-blockers, calcium channel blockers or thiazide diuretics) were included. The participants were followed for the occurrence of a kidney stone event while maintaining continuous usage on their drug class. The association between antihypertensive class and outcome was estimated by Cox regression. Of the 542 581 people included, we observed 4533 kidney stone events (0.83%) over a median follow-up of 368 days (365-729). Compared with beta-blockers, thiazides were associated with a lower risk of kidney stones (hazard ratio (HR) 0.76; 95% confidence interval (CI) 0.68-0.84), ACEis/ARBs with a borderline decreased risk (HR 0.90; 95% CI 0.83-0.98) and calcium channel blockers with a comparable risk (HR 1.02; 95% CI 0.92-1.13). When the risk of requiring an intervention for a kidney stone was examined, the results were consistent with the primary analysis; however, the protective effect of ACEis/ARBs was eliminated (HR 0.96; 95% CI 0.87-1.06). In conclusion, relative to beta-blockers, thiazide diuretics were associated with a decreased risk of kidney stone formation in adults aged >65 years, whereas ACEis/ARBs and calcium channel blockers had a comparable risk of presenting with a kidney stone.

  2. The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats

    PubMed Central

    Li, Guofu; Jia, Jia; Ji, Kaiqiang; Gong, Xiaoying; Wang, Rui; Zhang, Xiaoli; Wang, Haiyuan; Zang, Bin

    2016-01-01

    Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1β, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury. PMID:27430552

  3. Pathophysiological changes in rat kidneys with partial ureteral obstruction since infancy.

    PubMed

    Pettersson, B A; Aperia, A; Elinder, G

    1984-08-01

    A partial ureteral obstruction (PUO) was created in 5-day-old rats by implanting the left ureter in the psoas muscle. The surgical technique was modified to produce mild or severe hydronephrosis [Hn (m) and Hn (s)]. The rats were studied at ages between 45 and 65 days with regard to kidney weight, number of functioning glomeruli, mean arterial blood pressure (MAP), total glomerular filtration rate (GFR), nephron filtration rate (SNGFR), tubular free-flow pressure (PT, and stop-flow pressure (SFP). Total GFR was determined after the release of obstruction. The other studies were performed in the obstructed state. Reference values were obtained from sham-operated and untouched control rats. The number of functioning nephrons was depressed 38% in Hn (m) and 73% in Hn (s). Total GFR was preserved in Hn (m) and depressed 54% in Hn (s). SNGFR in the remaining nephrons was significantly elevated in Hn (m) and normal in Hn (s). SFP was significantly elevated in Hn (s). The Hn (s) rats were hypertensive. The glomerular density was lower in the hydronephrotic than in the contralateral kidneys. This suggests a compensatory growth of the remaining nephrons in the Hn kidneys. We conclude that PUO present since infancy will either destroy the nephrons or elicit an adaptive response that will tend to preserve GFR.

  4. The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats.

    PubMed

    Li, Guofu; Jia, Jia; Ji, Kaiqiang; Gong, Xiaoying; Wang, Rui; Zhang, Xiaoli; Wang, Haiyuan; Zang, Bin

    2016-09-01

    Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor‑α, interleukin-1β, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury.

  5. Motion corrected Cadence CPS ultrasound for quantifying response to vasoactive drugs in a rat kidney model

    PubMed Central

    Pollard, Rachel E.; Dayton, Paul A.; Watson, Katherine D.; Hu, Xiaowen; Guracar, Ismayil M.; Ferrara, Katherine W.

    2009-01-01

    Objective: To establish the ability of contrast enhanced motion corrected Cadence Pulse Sequencing (CPS) to detect changes in renal blood flow induced by vasoactive substances in rats. Methods: Ultrasound contrast media was administered as a constant rate infusion into a phantom at a known rate and CPS data acquired. Rats were anesthetized and pre-drug CPS estimates of replenishment rate were made for the right kidney. Real-time motion correction was applied and parametric images were generated from the CPS data. Group 1 rats (n=7) were administered a vasodilator and Group 2 rats (n=3) were given a vasoconstrictor. CPS imaging of the kidney was repeated following ample time for drug effects to occur. Results: Contrast CPS accurately estimated flow velocity in the phantom model. In addition, CPS defined statistically significant differences between pre and post drug blood flow in the renal medulla (vasodilator, p<0.01; vasoconstrictor, p<0.0001) and cortex (vasoconstrictor, p<0.0001). Conclusions: We conclude that motion corrected CPS ultrasound provides real time quantification of renal blood flow alterations and may prove useful for the assessment of blood flow in transplanted kidneys. PMID:19589583

  6. Increased albumin permeation in eyes, aorta, and kidney of hypertensive rats fed galactose

    SciTech Connect

    Tilton, R.G.; LaRose, L.; Chang, K.; Weigel, C.J.; Williamson, J.R.

    1986-03-01

    These experiments were undertaken to determine whether ingestion of galactose increases albumin permeation in the vasculature of hypertensive rats. 50% dextrin (control) or 50% galactose diets were fed to unilaterally nephrectomized, male Sprague-Dawley rats weighing 200 g. Hypertension (systolic pressure >175 mmHg) was induced by weekly IM injections of 25 mg/kg DOCA and 1% saline drinking water; 3 months later /sup 125/I-albumin permeation was assessed in whole eyes, aorta and kidneys. /sup 125/I-albumin permeation was significantly increased in all 3 tissues of hypertensive rats (n = 9) vs controls (n = 9): aorta (3.30 +/- 0.19 (SD) vs 2.87 +/- 0.14), eye (3.15 +/- 0.14 vs 2.59 +/- 0.11), and kidney (6.58 +/- 0.63 vs 3.85 +/- 0.50). Albumin permeation was increased still further in hypertensive rats fed the galactose diet (n = 8): aorta (3.75 +/- 0.38), eye (3.82 +/- 0.17), and kidney (10.74 +/- 3.13). Hypertension +/- galactose feeding had no effect on albumin permeation in lung, skin, or brain. These findings indicate that: (1) hypertension increases albumin permeation in vessels affected by diabetic vascular diseases, and 2) hypertension-induced increases in albumin permeation are increased still further by galactose ingestion, presumably mediated by imbalances in polyol/insitol metabolism (analogous to those induced by diabetes) independent of hyperglycemia and/or insulinopenia.

  7. Rutin ameliorates kidney interstitial fibrosis in rats with obstructive nephropathy.

    PubMed

    Wang, Bin; Liu, Ding; Zhu, Qiu-Hua; Li, Min; Chen, Hua; Guo, Ying; Fan, Li-Pei; Yue, Liang-Sheng; Li, Liu-Yang; Zhao, Ming

    2016-06-01

    Rutin reportedly conveys many beneficial effects, including renoprotection; however, it has not yet been demonstrated to have a renoprotective effect against obstructive nephropathy. The present study is the first to show a protective effect of rutin against obstructive renal injury induced by unilateral ureteral obstruction (UUO). A total of 24 male Wistar rats were randomly divided into four groups of six rats each, including vehicle- or rutin-treated sham operated groups, and vehicle- or rutin-treated UUO groups. Rats received daily oral gavage of rutin (100mg/kg) for 2weeks. All rats were euthanized on postoperative day 14. Histological findings showed that rutin administration significantly reduced renal interstitial injury and suppressed interstitial collagen deposits in UUO rats. Moreover, rutin decreased macrophage infiltration, proinflammatory cytokine expression and phosphorylation of nuclear factor-κB p65. Furthermore, rutin inhibited extracellular matrix accumulation by reducing expression of type I/III collagen and fibronectin. Rutin also prevented the epithelial-mesenchymal transition processes of renal tubular cells by decreasing α-smooth muscle actin expression and retaining E-cadherin expression. These effects of rutin were in parallel with the reductions in Smad3 activity and pivotal to the fibrogenic potential of TGF-β1. Taken together, the renoprotective effects of rutin in obstructive nephropathy were likely due to anti-inflammatory effects and inhibition of TGF-β1/Smad3 signaling.

  8. Urinary Biomarker Detection of Melamine- and Cyanuric Acid-Induced Kidney Injury in Rats

    PubMed Central

    Goering, Peter L.

    2012-01-01

    Oral coexposure of rats to melamine (MEL) and cyanuric acid (CYA) results in a dose-dependent increase in the formation of MEL-CYA crystals in the kidney. The aim of this study was to determine if urinary biomarkers of acute kidney injury could be used to noninvasively detect renal damage associated with crystal formation in the kidneys of MEL- and CYA-exposed rats. Urine was obtained on days 0 (predose), 2, 4, 14, and 28 from male and female Fischer 344 rats fed a diet supplemented with 0, 120, 180, or 240 ppm each of MEL and CYA. A number of urinary protein biomarkers (kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, osteopontin, albumin, alpha-GST, GST-Yb1, renal papillary antigen 1 [RPA-1], and clusterin) were measured using a multiplex assay system. The results showed that RPA-1 (distal tubule and collecting duct injury biomarker) was elevated on day 28 at the 120 ppm dose and higher in male rats and at the 180 ppm dose and higher in female rats; however, other urinary protein biomarkers were significantly elevated only at the 240 ppm dose. Significant elevation in blood urea nitrogen and serum creatinine levels, and severe renal damage evidenced by histopathology, were observed after 28 days of exposure to the highest dose, despite the fact that MEL-CYA crystals were observable at the 120 and 180 ppm doses. These data indicate that RPA-1 may serve as a noninvasive urinary biomarker for the detection and monitoring of obstructive nephropathy associated with MEL-CYA exposure. PMID:22610612

  9. A gene differentially expressed in the kidney of the spontaneously hypertensive rat cosegregates with increased blood pressure.

    PubMed Central

    Samani, N J; Lodwick, D; Vincent, M; Dubay, C; Kaiser, M A; Kelly, M P; Lo, M; Harris, J; Sassard, J; Lathrop, M

    1993-01-01

    The role of the kidney in initiating hypertension has been much debated. Here we demonstrate that a recently identified gene of yet unknown function, termed SA, which is differentially expressed in the kidney of the spontaneously hypertensive rat, cosegregates with an increase in blood pressure in F2 rats derived from a cross of the spontaneously hypertensive rat with normotensive Wistar-Kyoto rats, accounting for 28 and 21% of the genetic variability in systolic and diastolic blood pressures, respectively. Further, the genotype at this locus appears to determine the level of expression of the gene in the kidney. The findings provide strong evidence for a primary genetic involvement of the kidney in hypertension. Images PMID:8349793

  10. Intrarenal CYP-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats

    PubMed Central

    Walkowska, Agnieszka; Thumová, Monika; Škaroupková, Petra; Husková, Zuzana; Vaňourková, Zdenka; Chábová, Věra Čertíková; Tesař, Vladimír; Kramer, Herbert J.; Falck, John R.; Imig, John D.; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Červenka, Luděk

    2010-01-01

    Objective The contribution of cytochrome P-450 (CYP) metabolites of arachidonic acid: epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) in the regulation of nonclipped kidney function in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats during the phases of initial and stable hypertension (7 or 27 days after clipping, respectively) were investigated. Methods Male Hannover-Sprague Dawley rats had the right renal artery clipped or had a sham-operation. Urinary excretion of EETs, their inactive metabolites (DHETEs), and 20-HETE were measured. Intrarenal CYP protein expression and the activities of epoxygenase, ω-hydroxylase and soluble epoxide hydrolase (sEH) were also determined. The responses of renal hemodynamics and electrolyte excretion of the non-clipped kidney to left renal artery infusions of inhibitors of EETs or 20-HETE formation (MS-PPOH and DDMS, respectively) were measured. Results In 2K1C rats the urinary EETs excretion was lower and 20-HETE excretion was higher than in sham-operated animals. Intrarenal inhibition of EETs significantly decreased renal hemodynamics and sodium excretion in sham-operated but not in 2K1C rats. Intrarenal inhibition of 20-HETE decreased sodium excretion in sham-operated rats but elicited increases in renal hemodynamics and sodium excretion in 2K1C rats. Conclusions The results indicate that the nonclipped kidney of Goldblatt 2K1C rats in the phase of sustained hypertension exhibits decreased intrarenal EETs and elevated 20-HETE levels as compared with the kidney of sham-operated animals. This suggests that altered production and action of CYP-derived metabolites in this phase contributes to the mechanism of Goldblatt 2K1C hypertension. PMID:19940786

  11. The protective role of bee honey against the toxic effect of melamine in the male rat kidney.

    PubMed

    Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Solamy, Suad M

    2015-06-01

    This study aimed to test the protective role of natural bee honey against melamine toxicity in the kidney of male albino rats. The dietary supplementation of melamine at a dose of 20,000 ppm for 28 days induced renal dysfunction, as reflected by a significant increase in kidney function parameters (urea, creatinine, and uric acid) and an increase in potassium levels. In addition, a decrease in catalase and glutathione-S-transferase and an increase in lipid peroxide in the kidney tissue homogenate were also observed. Histological changes in the melamine-treated group revealed hyperplasia and damage in kidney cells and the accumulation of melamine crystals in kidney tissues. Honey treatment for 28 days in rats concurrently administered melamine at a dose of 2.5 g/kg body weight for 28 days improved the kidney function, increased antioxidant enzymes, and decreased lipid peroxide levels. The morphology of the kidney cells of the melamine-fed rats was also improved as a result of honey treatment. In conclusion, this study revealed that natural bee honey protects the kidney against the adverse effects induced by melamine toxicity in male albino rats.

  12. Kidney cancer in Canada: the rapidly increasing incidence of adenocarcinoma in adults and seniors.

    PubMed

    Liu, S; Semenciw, R; Morrison, H; Schanzer, D; Mao, Y

    1997-01-01

    To examine kidney cancer incidence and mortality patterns since 1969 in Canada. Linear regression of the log rates was used to estimate secular trends by age group and sex, and age-period-cohort models were fitted to examine changes in kidney cancer and renal adenocarcinoma incidence rates. A substantial increase in incidence rates was observed among those 35 years and older, with average increases of 2.5% or more annually for both sexes. Age-period-cohort modelling suggested that much of this increase resulted from a period effect. Changes in mortality were much more modest, especially among those aged 0-34, for whom mortality rates actually declined by an average of 4.2% and 5.4% annually for males and females respectively. Kidney cancer incidence rates have increased significantly, especially renal adenocarcinoma among adults and seniors. Diagnostic improvements and increasing levels of obesity in the Canadian population may have contributed to these trends.

  13. Characterization of ascorbic acid uptake by isolated rat kidney cells

    SciTech Connect

    Bowers-Komro, D.M.; McCormick, D.B. )

    1991-01-01

    Isolated kidney cells accumulated L(1-14C)ascorbic acid in a time-dependent manner and reached a steady state after 15 min at 37 degrees C. Initial velocity for uptake was over 300 pmol/mg protein per min when cells were separated from the bathing solution using a density gradient established during centrifugation. The uptake process was saturable with an apparent concentration at half maximal uptake of 36 mumols/L. Ascorbate uptake was reduced by metabolic inhibitors and was temperature dependent. Although ascorbic acid is an acid anion at pH 7.4, uptake did not appear to be inhibited by other acid anions such as p-aminohippurate and probenecid; however, involvement of the ion gradient established by Na+, H(+)-adenosine triphosphatase could not be confirmed. Replacing the sodium ion with other monovalent ions reduced the accumulation of ascorbate significantly. Isoascorbic and dehydroascorbic acids inhibited ascorbate uptake (34 and 13 mmol/L, respectively), whereas high concentrations of glucose showed some stimulation. These findings indicated that ascorbic acid is reabsorbed by the kidney in a sodium-dependent active transport process that is not common to other acid anions and has some specificity for the ascorbic acid structure.

  14. Progression of early phase diabetic nephropathy in streptozotocin-induced diabetic rats: evaluation of various kidney-related parameters.

    PubMed

    Kiran, G; Nandini, C D; Ramesh, H P; Salimath, P V

    2012-02-01

    Diabetic nephropathy (DN) is one of the serious secondary complications of diabetes, which results in end-stage renal failure. Reports on the progressive nature of early phase DN especially with respect to kidney parameters such as kidney weight, type IV collagen excretion, total kidney and urinary glycosaminoglycans (GAGs) are few. This work was undertaken to determine systematically the progression of early phase DN in relation to various kidney-related parameters for a period of four months. Experimentally-induced diabetic rats were grouped based on fasting blood glucose levels. Various basic and kidney-related parameters such as kidney weight, microalbuminuria, urinary excretion of GAGs and type IV collagen, total kidney GAGs, histopathology, glomerular area and glomerular volume were examined in control and diabetic rats. There was a progressive increase in fasting blood sugar, urine sugar, kidney weight, microalbuminuria, urine glycosaminoglycans, urine type IV collagen, glomerular area and glomerular volume but there was a progressive decrease in kidney glycosaminoglycans. Glomerular sclerotic condition was aggravated with the increase in duration of diabetes from 1 to 4 months. Onset of DN in rats begins subtly after one month of diabetes but gets vitiated and more pronounced at the end of four months.

  15. Effects of Aminoguanidine on Lipid and Protein Oxidation in Diabetic Rat Kidneys

    PubMed Central

    Küçükkaya, Belgin; Ersöz, H. önder; Yalçin, A. Süha; Emerk, Kaya; Akalin, Sema

    2002-01-01

    Nonenzymatic glycation of tissue and plasma proteins may stimulate the production of oxidant and carbonyl stress in diabetes. The aim of this study was to evaluate the effects of aminoguanidine (AG) on lipid peroxidation, protein oxidation and nitric oxide (NO) release in diabetic rat kidneys. After induction of diabetes with streptozotocin, female Wistar rats were divided into 2 groups. Group DAG (n=9) rats were given AG hydrogen carbonate (1 g/L) in drinking water and group D (n=8) was diabetic control rats given only tap water. Group H (n=8) was followed as healthy controls. At the end of an 8 week period, NO release, lipid and protein oxidation were determined in kidney tissues. NO release was significantly lower in diabetic rats compared with healthy controls (p<0.05). Lipid peroxidation was significantly high in group D (3.9 ± 0.3 nmol MDA/g tissue) compared with the group DAG (2.6 ± 0.1 nmol MDA/g tissue, p<0.01) and group H (2.4 ± 0.2 nmol MDA/g tissue). Protein oxidation was significantly higher in diabetics than healthy controls (563.8 ± 23.9, 655.8 ± 7.2 , 431.5 ± 8.8 mmol carbonyl / g tissue for group DAG, D and H, respectively, p< 0.05). A positive correlation between albuminuria and thiobarbituric acid reactive substance (TBARS) levels (r= 0.54,p<0.005) and carbonyl content (r=0.70, p<0.0005) in kidney homogenate were observed. Although AG treatment had no effect on NO release, it significantly decreased lipid peroxidation in diabetic rat cortices. Consequently increased lipid peroxidation -as well as- protein oxidation could be involved in the pathogenesis of diabetic albuminuria. PMID:11991200

  16. PHYSICAL ACTIVITY AND RAPID DECLINE IN KIDNEY FUNCTION AMONG OLDER ADULTS

    PubMed Central

    Robinson-Cohen, Cassianne; Katz, Ronit; Mozaffarian, Dariush; Dalrymple, Lorien S; de Boer, Ian; Sarnak, Mark; Shlipak, Mike; Siscovick, David; Kestenbaum, Bryan

    2010-01-01

    BACKGROUND Physical activity promotes diverse metabolic benefits that may moderate the long-term risk of progressive kidney dysfunction. OBJECTIVE To test the hypothesis that greater physical activity is associated with a lower risk of rapid kidney function decline among a general population of older adults. DESIGN Prospective cohort study of community-dwelling older men and women. SETTING Community-based sample in 4 U.S. sites recruited from Medicare eligibility files. PARTICIPANTS A total of 5888 men and women aged 65 years or older participating in the Cardiovascular Health Study. Participants who did not complete at least two measurements of kidney function, those who were unable to complete basic household chores, and those with missing physical activity data were excluded, leaving 4011 participants for analysis. MAIN EXPOSURE MEASURE Physical activity score calculated by summation of leisure-time activity (ordinal score of 1–5 for quintiles of 105, 480, 1012.5, and 2089 kilocalories per week) and walking pace (ordinal score of 1–3 for categories of less than 2, 2–3, and greater than 3 miles per hour). MAIN OUTCOME MEASURE Rapid kidney function decline, defined by the loss of >3.0 mL/min per 1.73 m2 per year in the estimated glomerular filtration rate, calculated using longitudinal serum measurements of cystatin C. RESULTS There were 958 participants (23.9%) with a rapid decline in kidney function, (4.1 events per 100 person-years). The estimated risk of rapid kidney function decline was 16% in the highest physical activity group and 30% in the lowest physical activity group. After full adjustment for demographics, clinical, and subclinical disease characteristics, the two highest physical activity groups were associated with a 28% lower (95% CI: 21% to 41% lower) risk of rapid kidney function decline, compared to the two lowest physical activity groups. Greater kilocalories of leisure time physical activity, walking pace, and exercise intensity were

  17. Acute compensatory adaptation of renal function following contralateral kidney exclusion in Brattleboro rats with diabetes insipidus.

    PubMed Central

    Shirley, D G; Skinner, J

    1978-01-01

    1. The function of the remaining kidney following ligation of a single renal pedicle in anaesthetized rats with hereditary hypothalamic diabetes insipidus (DI) was studied using clearance methods. Values were compared with those obtained in DI rats which had been sham operated. 2. A small increase in the glomerular filtration rate of the remaining kidney was observed, which was statistically significant after 150 min. Increases in effective renal plasma flow were also observed, but these were not statistically significant. 3. The fractional excretion rates of Na and K increased immediately after contralateral kidney ligation; as a result total Na and K excretion rates remained similar to values in sham operated animals with both kidneys intact. 4. Fractional urine flow (V/GFR) increased by approximately 40% after contralateral ligation. It is argued that, since water reabsorption in the diluting segments of the nephron was unlikely to have been reduced, the increase in V/GFR was an indication that fractional fluid reabsorption in the proximal nephron had been inhibited. 5. Clearance determinations showed that the fractional reabsorption of Na in the proximal nephron was similarly reduced after contralateral ligation. However, Na reabsorption in the distal nephron increased, though not by enough to prevent a doubling of fractional sodium excretion. 6. The osmolalities of interstitial fluids obtained from the medulla and papilla of the contralateral kidney 2 hr after unilateral renal pedicle ligation were slightly, but significantly, higher than corresponding values in sham operated rats. This raises the possibility that salt reabsorption in the ascending limb of Henle might be enhanced immediately after contralateral renal exclusion. PMID:722584

  18. Dose-Dependent Effect of Deltamethrin in Testis, Liver, and Kidney of Wistar Rats

    PubMed Central

    Sharma, Poonam; Singh, Rambir; Jan, Mysra

    2014-01-01

    Objectives: Deltamethrin is a synthetic pyrethroid insecticide used worldwide in agriculture, household pest control, protection of foodstuff, and disease vector control. Although initially thought to be least toxic, a number of recent reports showed its toxic effects in mammalian and non-mammalian animal species. The current study was performed to assess the dose-dependent deltamethrin toxicity on testes, liver, and kidney of male Wistar rats. Materials and Methods: Twenty-four rats were divided in four groups of 6 each. Group A served as normal control. Group B, C, and D were administered with different doses (2 or 3 or 6 mg/kg corresponding to 1/30th or 1/20th or 1/10th of LD50, respectively) of deltamethrin for 28 days. Results: Deltamethrin exposure caused a significant reduction in weight of reproductive organs, decrease in sperm count, sperm motility, serum testosterone (T), follicle stimulating hormones (FSH), and luteinizing hormones (LH) in testis. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) were decreased in testis, liver and kidney of exposed rats. Deltamethrin exposure significantly increased sperm abnormalities in testis. Significant increase in lipid peroxidation (LPO) level was observed in testis, liver and kidney. Deltamethrin also caused histological alterations in testes, liver, and kidney. Conclusions: The results indicated that deltamethrin at a dose of 6 mg/kg exerts significant harmful effects on testes, liver and kidney as compare to 2 mg and 3 mg/kg. The study concluded that the system toxicity induced by deltamethrin was dose dependent. PMID:25253921

  19. Kidney injury biomarkers in hypertensive, diabetic, and nephropathy rat models treated with contrast media.

    PubMed

    Rouse, Rodney L; Stewart, Sharron R; Thompson, Karol L; Zhang, Jun

    2013-01-01

    Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to determine the effect of CM administration on kidney injury biomarkers in the face of preexisting kidney injury. Spontaneously hypertensive rats (hypertension), streptozotocin-treated Sprague Dawley rats (diabetes), and Dahl salt-sensitive rats (protein-losing nephropathy) were given single intravenous injections of the nonionic, low osmolar contrast medium, iohexol. Blood urea nitrogen (BUN), serum creatinine (sCr), and urinary biomarkers; albumin, lipocalin 2 (Lcn-2), osteopontin (Opn), kidney injury molecule 1 (Kim-1), renal papillary antigen 1 (Rpa-1), α-glutathione S-transferase (α-Gst), µ-glutathione S-transferase (µ-Gst), and beta-2 microglobulin (β2m) were measured in disease models and appropriate controls to determine the response of these biomarkers to CM administration. Each disease model produced elevated biomarkers of kidney injury without CM. Preexisting histopathology was exacerbated by CM but little or no significant increases in biomarkers were observed. When 1.5-fold or greater sCr increases from pre-CM were used to define true positives, receiver-operating characteristic curve analysis of biomarker performance showed sCr was the best predictor of CIN across disease models. β2m, Lcn-2, and BUN were the best predictors of histopathology defined kidney injury.

  20. Oral nanoparticulate curcumin combating arsenic-induced oxidative damage in kidney and brain of rats.

    PubMed

    Sankar, Palanisamy; Telang, Avinash Gopal; Kalaivanan, Ramya; Karunakaran, Vijayakaran; Suresh, Subramaniyam; Kesavan, Manickam

    2016-03-01

    Arsenic exposure through drinking water causes oxidative stress and tissue damage in the kidney and brain. Curcumin (CUR) is a good antioxidant with limited clinical application because of its hydrophobic nature and limited bioavailability, which can be overcome by the encapsulation of CUR with nanoparticles (NPs). The present study investigates the therapeutic efficacy of free CUR and NP-encapsulated CUR (CUR-NP) against sodium arsenite-induced renal and neuronal oxidative damage in rat. The CUR-NP prepared by emulsion technique and particle size ranged between 120 and 140 nm, with the mean particle size being 130.8 nm. Rats were divided into five groups (groups 1-5) with six animals in each group. Group 1 served as control. Group 2 rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5 were treated with arsenic as in Group 2; however, these animals were also administered with empty NPs, CUR (100 mg/kg body weight), and CUR-NP (100 mg/kg), respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic exposure significantly increased serum urea nitrogen and creatinine levels. Arsenic increased lipid peroxidation (LPO), reduced glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were depleted significantly in both kidney and brain. Treatment with free CUR and CUR-NP decreased the LPO and increased the enzymatic and nonenzymatic antioxidant system in kidney and brain. Histopathological examination showed that kidney and brain injury mediated by arsenic was ameliorated by treatment. However, the amelioration percentage indicates that CUR-NP had marked therapeutic effect on arsenic-induced oxidative damage in kidney and brain tissues.

  1. Identification and Characterization of Phytohemagglutinins from White Kidney Beans (Phaseolus vulgaris L., var. Beldia) in the Rat Small Intestine.

    PubMed

    Nciri, Nader; Cho, Namjun; El Mhamdi, Faiçal; Ben Mansour, Abderraouf; Haj Sassi, Fayçal; Ben Aissa-Fennira, Fatma

    2016-01-01

    Although kidney bean (Phaseolus vulgaris L.) lectin toxicity is widely known, its effects in the gastrointestinal tract require further study. This investigation aimed to identify and characterize phytohemagglutinins (PHAs) in the small intestine and sera of rats following oral challenge with ground white beans. Twenty young, adult male rats were divided randomly into two groups of 10 animals each. The control group underwent gavage with a suspension of 300 mg of rodent pellet flour. The experimental group was administered a 300 mg Beldia bean flour suspension (BBFS). After 10 days of daily treatment, jejunal rinse liquid (JRL) and ileum rinse liquid and secretions, as well as sera, were collected. All biological fluids were screened for lectin reactivity using competitive inhibition ELISA, Ouchterlony double immunodiffusion, and immunoelectrophoresis techniques. The results revealed the presence of immunogenic intraluminal PHAs 3-4 h after the oral intake of the BBFS in the JRLs as well as in the jejunal and ileal secretions; however, no PHA was detectable in the rat sera. Ingestion of raw Beldia beans may lead to interaction between PHAs and the mucosa of the small intestine, potentially resulting in an inflammatory response.

  2. Gestational and postnatal protein deficiency affects postnatal development and histomorphometry of liver, kidneys, and ovaries of female rats' offspring.

    PubMed

    Almeida, Fernanda R C L; Silva, Gerluza A B; Fiúza, Aparecida T L; Chianca, Deoclécio A; Ferreira, Anderson J; Chiarini-Garcia, Hélio

    2012-04-01

    Pre- and postnatal protein deficiency may lead to decreased foetal intra-uterine development and postnatal growth, which is common in developing countries. The present study aimed to investigate the consequences of a low-protein intake during gestation and postnatally on adult female rats' offspring. Female rats were given either a control or a protein-deficient diet throughout the gestation and lactation periods. A subset of females was killed at day 20 of pregnancy for foetal and placental measurements. Another subset of females farrowed and the number, length, and weight of the offspring were measured. After weaning, the offspring received the same diet as their dams until 70 days of age. They were sacrificed, and some organs were weighed and collected for histomorphometrical analyses. Placental weight and size and foetal weight were lower in protein-deficient dams. The weight and length of pups at birth were also lower in the deficient group. The organs to body weight ratio were higher in the deficient animals at 70 days of age. The protein-deficient female offspring had a smaller ovarian area, greater numbers of primordial follicles and developing follicles per square millimetres of ovarian cortex, and no corpora lutea. The liver showed smaller nuclear diameter of the hepatocytes and height of the hepatocytes cords. The kidneys showed smaller cortical area with reduced glomerular number and diameter. These results provide the first evidence of the histomorphological changes of the association between gestational and postnatal protein deficiency in female rats' offspring.

  3. Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats.

    PubMed

    Burukoglu, Dilek; Baycu, Cengiz; Taplamacioglu, Fulya; Sahin, Erhan; Bektur, Ezgi

    2016-06-01

    Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration. © The Author(s) 2014.

  4. Urine Metabolites Reflect Time-Dependent Effects of Cyclosporine and Sirolimus on Rat Kidney Function☆

    PubMed Central

    Klawitter, Jost; Bendrick-Peart, Jamie; Rudolph, Birgit; Beckey, Virginia; Klawitter, Jelena; Haschke, Manuel; Rivard, Christopher; Chan, Laurence; Leibfritz, Dieter; Christians, Uwe; Schmitz, Volker

    2009-01-01

    Background The clinical use of the immunosuppressant calcineurin inhibitor cyclosporine is limited by its nephrotoxicity. This is enhanced when combined with the immunosuppressive mTOR inhibitor sirolimus. Nephrotoxicity of both drugs is not yet fully understood. Methods The goal was to gain more detailed mechanistic insights into the time-dependent effects of cyclosporine and sirolimus on the rat kidney by using a comprehensive approach including metabolic profiling in urine (1H-NMR spectroscopy), kidney histology, kidney function parameters in plasma, measurement of glomerular filtration rates, the oxidative stress marker 15-F2t-isoprostane in urine and immunosuppressant concentrations in blood and kidney. Male Wistar rats were treated with vehicle (controls), cyclosporine (10/25mg/kg/d) and/or sirolimus (1mg/kg/d) by oral gavage once daily for 6 and 28 days. Results Twenty-eight day treatment led to a decrease of glomerular filtration rates (cyclosporine -59%, sirolimus -25%). These were further decreased when both drugs were combined (-86%). Histology revealed tubular damage after treatment with cyclosporine, which was enhanced when sirolimus was added. No other part of the kidney was affected. 1H-NMR spectroscopy analysis of urine (day 6) revealed time-dependent changes of 2-oxoglutarate, citrate and succinate concentrations. In combination with increased urine isoprostane concentrations these changes indicated oxidative stress. After 28 days of cyclosporine treatment, urine metabonomics shifted to patterns typical for proximal tubular damage with reduction of Krebs cycle intermediates and trimethylamine-N-oxide concentrations whereas acetate, lactate, trimethylamine and glucose concentrations increased. Again, sirolimus enhanced these negative effects. Conclusions Our results indicate that cyclosporine and/or sirolimus induce damage of the renal tubular system. This is reflected by urine metabolite patterns, which seem to be more sensitive than currently used

  5. Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

    PubMed

    Ragy, Merhan Mamdouh

    2015-01-01

    Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p < 0.05), while serum catecholamines were insignificantly higher in the exposed rats. These alterations were corrected by withdrawal. In conclusion, electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.

  6. Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.

    PubMed

    Asahina, Makoto; Shimizu, Fumi; Ohta, Masayuki; Takeyama, Michiyasu; Tozawa, Ryuichi

    2015-01-01

    Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.

  7. Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction

    PubMed Central

    ASAHINA, Makoto; SHIMIZU, Fumi; OHTA, Masayuki; TAKEYAMA, Michiyasu; TOZAWA, Ryuichi

    2015-01-01

    Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome. PMID:25912321

  8. Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.

    PubMed

    Sugiura, Takahiro; Kobuchi, Shuhei; Tsutsui, Hidenobu; Takaoka, Masanori; Fujii, Toshihide; Hayashi, Kentaro; Matsumura, Yasuo

    2009-01-28

    The excitation of renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury in rats. Recently, we found that agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the enhanced renal sympathetic nerve activity during renal ischemia and by decreasing the renal venous norepinephrine overflow after reperfusion. In the present study, we investigated preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine on the enhanced renal sympathetic nerve activity during renal ischemia and on the elevated norepinephrine overflow after reperfusion, and eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg, i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine overflow, without affecting the lowering effect of agmatine on renal sympathetic nerve activity. These results indicate that agmatine prevents the ischemic renal injury by sympathoinhibitory effect probably via I(1) receptors in central nervous system and by suppressing the norepinephrine overflow through alpha(2) or I(1) receptors on sympathetic nerve endings.

  9. Indigofera oblongifolia mitigates lead-acetate-induced kidney damage and apoptosis in a rat model.

    PubMed

    Dkhil, Mohamed A; Al-Khalifa, Mohamed S; Al-Quraishy, Saleh; Zrieq, Rafat; Abdel Moneim, Ahmed Esmat

    2016-01-01

    This study was conducted to appraise the protective effect of Indigofera oblongifolia leaf extract on lead acetate (PbAc)-induced nephrotoxicity in rats. PbAc was intraperitoneally injected at a dose of 20 mg/kg body weight for 5 days, either alone or together with the methanol extract of I. oblongifolia (100 mg/kg). Kidney lead (Pb) concentration; oxidative stress markers including lipid peroxidation, nitrite/nitrate, and glutathione (GSH); and antioxidant enzyme activities, namely superoxide dismutase, catalase, GSH peroxidase, and GSH reductase were all determined. The PbAc injection elicited a marked elevation in Pb concentration, lipid peroxidation, and nitrite/nitrate, with a concomitant depletion in GSH content compared with the control and a remarkable decrease in antioxidant enzymes. Oxidant/antioxidant imbalance, Pb accumulation, and histological changes in the kidneys were successfully prevented by the pre-administration of I. oblongifolia extract. In addition, the elevated expression of proapoptotic protein, Bax, in the kidneys of the PbAc-injected rats was reduced as a result of I. oblongifolia pre-administration, while the hitherto reduced expression of the anti-apoptotic protein Bcl-2 was elevated. Based on the current findings, it can be concluded that I. oblongifolia successfully minimizes the deleterious effects in kidney function and histological coherence associated with nephrotoxicity by strengthening the antioxidant defense system, suppressing oxidative stress, and mitigating apoptosis.

  10. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia.

    PubMed

    Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Bronze-da-Rocha, Elsa; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

    2015-12-25

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy.

  11. Expression and immunolocalization of AQP6 in intercalated cells of the rat kidney collecting duct.

    PubMed

    Ohshiro, K; Yaoita, E; Yoshida, Y; Fujinaka, H; Matsuki, A; Kamiie, J; Kovalenko, P; Yamamoto, T

    2001-08-01

    The expression and localization of AQP6 were examined in rat kidneys. In the kidney compartments, the expression was more intense in the outer medulla than in the cortex or inner medulla, and was negative in the glomerulus. During development, the AQP6 mRNA expression in the kidney was not detected in the fetus, but was recognized at birth, increased gradually by 4 weeks of age, and was unchanged thereafter. In situ hybridization demonstrated significant signals for AQP6 mRNA along the outer and inner medullary collecting ducts. Since the localization of the AQP6 mRNA-expressing cells was comparable to that of immunoreactive H+ ATPase-bearing cells in the collecting duct, they were identified as intercalated cells. No AQP6 mRNA signals were recognizable in other cells in the kidneys, including glomerular cells. No glomerular expression of AQP6 mRNA was confirmed by RT-PCR using total RNA extracted from the glomeruli. Immunohistochemistry using an antibody raised against recombinant rat AQP6 protein could localize the immunoreactivity in a population of collecting duct cells. Serial section observations indicated that the AQP6-immunoreactive cells corresponded to H+ ATPase bearing intercalated cells.

  12. Effect of spent turmeric on kidney glycoconjugates in streptozotocin-induced diabetic rats

    PubMed Central

    2014-01-01

    Background Curcumin known to have number of medicinal use and masked the fiber containing ukonan like active polysaccharide in turmeric and its pharmacological effect will be addressed on diabetic nephropathy particularly the glycoconjugates of extracellular components viz., glycoproteins and glycosaminoglycans - heparan sulfate (HS). Methods Male Wistar rats were maintained on AIN-76 diet containing 10% spent turmeric and were grouped into control and STZ induced diabetes SFC/TFC and SFD/TFD, respectively. Diabetic status was monitored using blood and urine, and at the end, harvested kidneys were used to study the amelioration of glycoprotiens (collagen) and HS by enzymatic digestion, spectrophotometric, hydroxyproline and agarose electrophoretic methods. Results In the present study spent turmeric (10%) fed diabetic rats showed improved glomerular filtration rate (50%), kidney enlargement (60%) and other glycoconjugate metabolism in kidney. Increased collagen content in diabetic group was observed by hydroxyproline estimation (24%) and periodic acid-Schiff’s (PAS) staining. Furthermore, elevated activities of enzymes involved in the synthesis and degradation of glycosaminoglycans (GAGs) were significantly lowered in spent turmeric fed diabetic group. Improvement in total GAGs (43%) and sulfate content (18%) followed by fractionation of GAGs using specific enzymes led to HS (28%) in the spent turmeric fed diabetic group, when compared to starch fed diabetic group and was further confirmed by electrophoresis of GAG. Conclusion These results clearly indicate beneficial role of spent turmeric in controlling glycoconjugates such as glycoproteins and heparan sulfate related kidney complications during diabetes. PMID:26413492

  13. Uranium XAFS analysis of kidney from rats exposed to uranium

    PubMed Central

    Kitahara, Keisuke; Numako, Chiya; Terada, Yasuko; Nitta, Kiyohumi; Homma-Takeda, Shino

    2017-01-01

    The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U L III-edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate. PMID:28244440

  14. Uranium XAFS analysis of kidney from rats exposed to uranium.

    PubMed

    Kitahara, Keisuke; Numako, Chiya; Terada, Yasuko; Nitta, Kiyohumi; Shimada, Yoshiya; Homma-Takeda, Shino

    2017-03-01

    The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U LIII-edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate.

  15. Indigofera oblongifolia mitigates lead-acetate-induced kidney damage and apoptosis in a rat model

    PubMed Central

    Dkhil, Mohamed A; Al-Khalifa, Mohamed S; Al-Quraishy, Saleh; Zrieq, Rafat; Abdel Moneim, Ahmed Esmat

    2016-01-01

    This study was conducted to appraise the protective effect of Indigofera oblongifolia leaf extract on lead acetate (PbAc)-induced nephrotoxicity in rats. PbAc was intraperitoneally injected at a dose of 20 mg/kg body weight for 5 days, either alone or together with the methanol extract of I. oblongifolia (100 mg/kg). Kidney lead (Pb) concentration; oxidative stress markers including lipid peroxidation, nitrite/nitrate, and glutathione (GSH); and antioxidant enzyme activities, namely superoxide dismutase, catalase, GSH peroxidase, and GSH reductase were all determined. The PbAc injection elicited a marked elevation in Pb concentration, lipid peroxidation, and nitrite/nitrate, with a concomitant depletion in GSH content compared with the control and a remarkable decrease in antioxidant enzymes. Oxidant/antioxidant imbalance, Pb accumulation, and histological changes in the kidneys were successfully prevented by the pre-administration of I. oblongifolia extract. In addition, the elevated expression of proapoptotic protein, Bax, in the kidneys of the PbAc-injected rats was reduced as a result of I. oblongifolia pre-administration, while the hitherto reduced expression of the anti-apoptotic protein Bcl-2 was elevated. Based on the current findings, it can be concluded that I. oblongifolia successfully minimizes the deleterious effects in kidney function and histological coherence associated with nephrotoxicity by strengthening the antioxidant defense system, suppressing oxidative stress, and mitigating apoptosis. PMID:27330278

  16. Protective effect of propolis on methotrexate-induced kidney injury in the rat.

    PubMed

    Ulusoy, Hasan Basri; Öztürk, İsmet; Sönmez, Mehmet Fatih

    2016-06-01

    Objectives Propolis is a potent antioxidant and a free radical scavenger. Pharmacological induction of heat shock proteins (HSPs) has been investigated for restoring normal cellular function following an injury. In this study, effect of propolis on HSP-70 expression in methotrexate-induced nephrotoxicity and direct preventive effect of propolis in this toxicity were investigated. Material and methods A total of 40 male Wistar albino rats were divided into four groups: Group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20 mg/kg. Groups 3 and 4 received 100 mg/kg/day propolis (by oral gavage) for 15 d by the first day of the experimental protocol. Then the rats were decapitated under ketamine esthesia and their kidney tissues were removed. HSP-70 expression, apoptosis, and histopathological damage scores were then compared. Results MTX caused epithelial desquamation into the lumen of the tubules, dilatation, and congestion of the peritubular vessels and renal corpuscles with obscure Bowman's space. The number of apoptotic cells (p = 0.000) and HSP-70 (p = 0.002) expression were increased in group 2. Propolis prevented the rise in number of apoptotic cells (p = 0.017), HSP-70 (p = 0.000) expression, and improved kidney morphology. Conclusions It was found that methotrexate gives rise to serious damage in the kidney and propolis is a potent antioxidant agent in preventing kidney injury.

  17. Epoxyeicosatrienoic acid analogue mitigates kidney injury in a rat model of radiation nephropathy.

    PubMed

    Hye Khan, Md Abdul; Fish, Brian; Wahl, Geneva; Sharma, Amit; Falck, John R; Paudyal, Mahesh P; Moulder, John E; Imig, John D; Cohen, Eric P

    2016-04-01

    Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by CYP epoxygenases, and EETs are kidney protective in multiple pathologies. We determined the ability of an EET analogue, EET-A, to mitigate experimental radiation nephropathy. The kidney expression of the EET producing enzyme CYP2C11 was lower in rats that received total body irradiation (TBI rat) compared with non-irradiated control. At 12 weeks after TBI, the rats had higher systolic blood pressure and impaired renal afferent arteriolar function compared with control, and EET-A or captopril mitigated these abnormalities. The TBI rats had 3-fold higher blood urea nitrogen (BUN) compared with control, and EET-A or captopril decreased BUN by 40-60%. The urine albumin/creatinine ratio was increased 94-fold in TBI rats, and EET-A or captopril attenuated that increase by 60-90%. In TBI rats, nephrinuria was elevated 30-fold and EET-A or captopril decreased it by 50-90%. Renal interstitial fibrosis, tubular and glomerular injury were present in the TBI rats, and each was decreased by EET-A or captopril. We further demonstrated elevated renal parenchymal apoptosis in TBI rats, which was mitigated by EET-A or captopril. Additional studies revealed that captopril or EET-A mitigated renal apoptosis by acting on the p53/Fas/FasL (Fas ligand) apoptotic pathway. The present study demonstrates a novel EET analogue-based strategy for mitigation of experimental radiation nephropathy by improving renal afferent arteriolar function and by decreasing renal apoptosis.

  18. EPOXYEICOSATRIENOIC ACID ANALOG MITIGATES KIDNEY INJURY IN A RAT MODEL OF RADIATION NEPHROPATHY

    PubMed Central

    Khan, Abdul Hye; Fish, Brian; Wahl, Geneva; Sharma, Amit; Falck, John R.; Paudyal, Mahesh P.; Moulder, John E.; Imig, John D.; Cohen, Eric P.

    2016-01-01

    Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by CYP-epoxygenases, and EETs are kidney protective in multiple pathologies. We determined the ability of an EET analog, EET-A, to mitigate experimental radiation nephropathy. The kidney expression of the EET producing enzyme CYP2C11 was lower in rats that received total body irradiation (TBI rat) compared to non-irradiated control. At 12 weeks after TBI, the rats had higher systolic blood pressure and impaired renal afferent arteriolar function compared to control, and EET-A or captopril mitigated these abnormalities. The TBI rats had 3-fold higher blood urea nitrogen compared to control, and EET-A or captopril decreased BUN by 40–60%. The urine albumin/creatinine ratio was increased 94-fold in TBI rats, and EET-A or captopril attenuated that increase by 60–90%. In TBI rats, nephrinuria was elevated 30-fold and EET-A or captopril decreased it by 50–90%. Renal interstitial fibrosis, tubular, and glomerular injury were present in the TBI rats, and each was decreased by EET-A or captopril. We further demonstrated elevated renal parenchymal apoptosis in TBI rats, which EET-A or captopril mitigated. Additional studies revealed that captopril or EET-A mitigated renal apoptosis by acting on p53/Fas/FasL apoptotic pathway. Overall, this study demonstrates a novel EET-analog based strategy for mitigation of experimental radiation nephropathy by improving renal afferent arteriolar function and by decreasing renal apoptosis. PMID:26772189

  19. Destructive and regenerative changes in the albino rat kidney during mercuric chloride necrotizing nephrosis

    SciTech Connect

    Andreev, V.P.

    1985-08-01

    This paper describes the results of a morphological analysis of destructive and regenerative changes observed during a study of serial semithin sections of the kidneys of albino rats with mercuric chloride necrotizing nephrosis. The results of this investigation indicate that injury to the epithelium of the urinary tubules by mercuric chloride is heterogenous in depth, and this has a substantial influence on the viability of the animals and on the subsequent process of repair of the damage.

  20. T lymphocytes mediate hypertension and kidney damage in Dahl salt-sensitive rats.

    PubMed

    De Miguel, Carmen; Das, Satarupa; Lund, Hayley; Mattson, David L

    2010-04-01

    This study examined mechanisms by which immune cells participate in the development of hypertension and renal disease in Dahl salt-sensitive (SS) rats. Increasing dietary salt from 0.4% to 4.0% NaCl significantly increased renal infiltration of T lymphocytes from 8.8 +/- 1.2 x 10(5) to 14.4 +/- 2.0 x 10(5) cells/2 kidneys, increased arterial blood pressure from 131 +/- 2 to 165 +/- 6 mmHg, increased albumin excretion rate from 17 +/- 3 to 129 +/- 20 mg/day, and resulted in renal glomerular and tubular damage. Furthermore, renal tissue ANG II was not suppressed in the kidneys of SS rats fed 4.0% NaCl. Administration of the immunosuppressive agent mycophenolate mofetil (MMF; 20 mg.kg(-1).day(-1)) prevented the infiltration of T lymphocytes and attenuated Dahl SS hypertension and renal disease. In contrast to vehicle-treated rats, Dahl SS rats administered MMF demonstrated a suppression of renal tissue ANG II from 163 +/- 26 to 88 +/- 9 pg/g of tissue when fed high salt. Finally, it was demonstrated that the T lymphocytes isolated from the kidney possess renin and angiotensin-converting enzyme activity. These data indicate that infiltrating T cells are capable of participating in the production of ANG II and are associated with increased intrarenal ANG II, hypertension, and renal disease. The suppression of T-cell infiltration decreased intrarenal ANG II and prevented Dahl SS hypertension and kidney damage. As such, infiltrating cells are capable of participating in the established phase of Dahl SS hypertension.

  1. A high affinity kidney targeting by chitobionic acid-conjugated polysorbitol gene transporter alleviates unilateral ureteral obstruction in rats.

    PubMed

    Islam, Mohammad Ariful; Kim, Sanghwa; Firdous, Jannatul; Lee, Ah-Young; Hong, Seong-Ho; Seo, Min Kyeong; Park, Tae-Eun; Yun, Cheol-Heui; Choi, Yun-Jaie; Chae, Chanhee; Cho, Chong-Su; Cho, Myung-Haing

    2016-09-01

    Aside from kidney transplantation - a procedure which is exceedingly dependent on donor-match and availability leading to excessive costs - there are currently no permanent treatments available which reverse kidney injury and failure. However, kidney-specific targeted gene therapy has outstanding potential to treat kidney-related dysfunction. Herein we report a novel kidney-specific targeted gene delivery system developed through the conjugation of chitobionic acid (CBA) to a polysorbitol gene transporter (PSGT) synthesized from sorbitol diacrylate and low molecular weight polyethylenimine (PEI) carrying hepatocyte growth factor (HGF) gene to alleviate unilateral ureteral obstruction (UUO) in rats. CBA-PSGT performed exceptionally well for targeted delivery of HGF to kidney tissues compared to its non-targeted counterparts (P < 0.001) after systemic tail-vein injection and significantly reduced the UUO symptoms, returning the UUO rats to a normal health status. The kidney-targeted CBA-PSGT-delivered HGF also strikingly reduced various pathologic and molecular markers in vivo such as the level of collagens (type I and II), blood urea nitrogen (BUN), creatinine, and the expressions of ICAM-1, TIMP-1 and α-SMA which play a critical role in obstructive kidney functions. Therefore, CBA-PSGT should be further investigated because of its potential to alleviate UUO and kidney-related diseases using high affinity kidney targeting.

  2. Epidemiology of chronic kidney disease in adults of Salvadoran agricultural communities.

    PubMed

    Orantes, Carlos M; Herrera, Raúl; Almaguer, Miguel; Brizuela, Elsy G; Núñez, Lilian; Alvarado, Nelly P; Fuentes, E Jackeline; Bayarre, Héctor D; Amaya, Juan Carlos; Calero, Denis J; Vela, Xavier F; Zelaya, Susana M; Granados, Delmy V; Orellana, Patricia

    2014-04-01

    In El Salvador, chronic kidney disease is a serious and growing public health problem. Chronic renal failure was the first cause of hospital deaths in men and the fifth in women in 2011. Determine prevalence of CKD, CKD risk factors (traditional and nontraditional) and renal damage markers in the adult population of specific rural areas in El Salvador; measure population distribution of renal function; and identify associated risk factors in CKD patients detected. A cross-sectional analytical epidemiological study was conducted based on active screening for chronic kidney disease and risk factors in persons aged ≥18 years during 2009-2011. Epidemiological and clinical data were gathered through personal history, as well as urinalysis for renal and vascular damage markers, determinations of serum creatinine and glucose, and estimation of glomerular filtration rates. Chronic kidney disease cases were confirmed at three months. Multiple logistical regression was used for statistical analysis. Prevalence of chronic kidney disease was 18% (23.9% for men and 13.9% for women) in 2388 persons: 976 men and 1412 women from 1306 families studied. Chronic kidney disease with neither diabetes nor hypertension nor proteinuria ≥1 g/L (51.9%) predominated. Prevalence of chronic renal failure was 11% (17.1% in men and 6.8% in women). Prevalence of renal damage markers was 12.5% (higher in men): microalbuminuria, 6.9%; proteinuria (0.3 g/L), 1.7%; proteinuria (1g/L), 0.6%; proteinuria (2 g/L), 0.4 %; and hematuria, 1.5%. Prevalence of chronic kidney disease risk factors was: diabetes mellitus, 9%; hypertension, 20.9%; family history of chronic kidney disease, 16.5%; family history of diabetes mellitus, 18.5%; family history of hypertension, 30.6%; obesity, 21%; central obesity, 24.9%; NSAID use, 84.2%; smoking, 9.9%; alcohol use, 15%; agricultural occupation, 31.2%; and contact with agrochemicals, 46.7%. Chronic kidney disease was significantly associated with male sex, older

  3. Alkalosis and renal excretion of ammonia by rat kidney.

    PubMed

    Solomon, S

    1988-05-15

    Upon sulfate administration, UpH falls more in alkalotic rats than in controls. Alkalosis can lead to a reduction in UNH3 V at highly acidic urine. The significance of this process is doubtful at UpH ranging from about 6 to 7. At lower UpH less NH3 would be excreted, thereby less H+ would be trapped in urine and some acid would be conserved.

  4. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy

    PubMed Central

    Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  5. Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

    PubMed Central

    Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

    2017-01-01

    Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

  6. Untargeted plasma and tissue metabolomics in rats with chronic kidney disease given AST-120

    PubMed Central

    Velenosi, Thomas J.; Hennop, Anzel; Feere, David A.; Tieu, Alvin; Kucey, Andrew S.; Kyriacou, Polydoros; McCuaig, Laura E.; Nevison, Stephanie E.; Kerr, Michael A.; Urquhart, Bradley L.

    2016-01-01

    Chronic kidney disease (CKD) results in the accumulation of metabolic waste products that are normally cleared by the kidney, known as uremia. Many of these waste products are from bacteria metabolites in the gut. Accumulation of uremic toxins in plasma and tissue, as well as the gut-plasma-tissue metabolic axis are important for understanding pathophysiological mechanisms of comorbidities in CKD. In this study, an untargeted metabolomics approach was used to determine uremic toxin accumulation in plasma, liver, heart and kidney tissue in rats with adenine-induced CKD. Rats with CKD were also given AST-120, a spherical carbon adsorbent, to assess metabolic changes in plasma and tissues with the removal of gut-derived uremic toxins. AST-120 decreased >55% of metabolites that were increased in plasma, liver and heart tissue of rats with CKD. CKD was primarily defined by 8 gut-derived uremic toxins, which were significantly increased in plasma and all tissues. These metabolites were derived from aromatic amino acids and soy protein including: indoxyl sulfate, p-cresyl sulfate, hippuric acid, phenyl sulfate, pyrocatechol sulfate, 4-ethylphenyl sulfate, p-cresol glucuronide and equol 7-glucuronide. Our results highlight the importance of diet and gut-derived metabolites in the accumulation of uremic toxins and define the gut-plasma-tissue metabolic axis in CKD. PMID:26932318

  7. Effect of Eclipta prostrata on 11Beta-Hydroxysteroid Dehydrogenase in Rat Liver and Kidney.

    PubMed

    Xu, Chenshu; Wei, Binghua; Fu, Xiaohua; Luo, Meijuan; Liu, Shidai; Li, Ruiming; Ren, Bin; Tang, Lei

    2014-01-01

    Eclipta prostrata (EP) is often prescribed in combination with glucocorticoid to treat glomerular nephritis, nephrotic syndrome, and IgA nephropathy in clinical practice of Traditional Chinese Medicine. Previous studies from our laboratory revealed that coadministration of EP significantly increased the plasma concentration of prednisolone while decreased the level of cotreated prednisone in rats. However, the underlying mechanism remains unclear. 11 β -Hydroxysteroid dehydrogenase (11 β -HSD) belongs to the family of oxidoreductases that catalyze the interconversion of prednisone to active prednisolone. Therefore, the current study aimed to investigate the effects of EP on the activity and expression of 11 β -HSD in rat liver and kidney. The results showed that oral administration of EP significantly increased the activity of 11 β -HSD I in the liver and 11 β -HSD II in the kidney by employing the microsomal incubation system. Moreover, gene and protein expressions of 11 β -HSD I and 11 β -HSD II were also increased in rat liver and kidney, respectively. These results suggest that the effects of EP on 11 β -HSD may attribute to the mechanism that administration of EP improves the efficacy and reduces adverse drug reactions of glucocorticoid in patients undergoing combinational therapy.

  8. Effect of Eclipta prostrata on 11Beta-Hydroxysteroid Dehydrogenase in Rat Liver and Kidney

    PubMed Central

    Xu, Chenshu; Wei, Binghua; Fu, Xiaohua; Luo, Meijuan; Liu, Shidai; Li, Ruiming; Ren, Bin; Tang, Lei

    2014-01-01

    Eclipta prostrata (EP) is often prescribed in combination with glucocorticoid to treat glomerular nephritis, nephrotic syndrome, and IgA nephropathy in clinical practice of Traditional Chinese Medicine. Previous studies from our laboratory revealed that coadministration of EP significantly increased the plasma concentration of prednisolone while decreased the level of cotreated prednisone in rats. However, the underlying mechanism remains unclear. 11β-Hydroxysteroid dehydrogenase (11β-HSD) belongs to the family of oxidoreductases that catalyze the interconversion of prednisone to active prednisolone. Therefore, the current study aimed to investigate the effects of EP on the activity and expression of 11β-HSD in rat liver and kidney. The results showed that oral administration of EP significantly increased the activity of 11β-HSD I in the liver and 11β-HSD II in the kidney by employing the microsomal incubation system. Moreover, gene and protein expressions of 11β-HSD I and 11β-HSD II were also increased in rat liver and kidney, respectively. These results suggest that the effects of EP on 11β-HSD may attribute to the mechanism that administration of EP improves the efficacy and reduces adverse drug reactions of glucocorticoid in patients undergoing combinational therapy. PMID:24876875

  9. Kidney and lung injury in irradiated rats protected from acute death by partial-body shielding

    SciTech Connect

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.; Michieli, B.M. )

    1990-04-01

    Ninety-six CD-1 male rats were exposed to gamma-ray doses (0-25 Gy) in increments of 5 Gy. One femur, the surgically exteriorized GI tract, and the oral cavity were shielded during irradiation to protect against acute mortality from injury to the hematopoietic system, small intestine, and oral cavity. In addition, the thoraxes of half of the animals from each dose group were shielded. At approximately monthly intervals from 2 to 10 months after irradiation the hematocrit, plasma urea nitrogen (PUN), and {sup 51}Cr-EDTA clearance were measured. During the study 20 thorax-shielded and 19 thorax-irradiated animals died. All rats whose thoraxes received 25 Gy irradiation and three out of seven rats whose thoraxes received 20 Gy died 1 to 3 months postirradiation with massive pleural fluid accumulation. Shielding the thoraxes prevented this mode of death at these doses. Kidney injury was judged to be the primary cause of death of all thorax-shielded animals and 15- and 20-Gy thorax-irradiated animals. Animals with kidney damage had elevated PUN and reduced {sup 51}Cr-EDTA clearance and hematocrits. The relative merits of each of these end points in assessing radiation-induced kidney injury after total-body exposure are discussed.

  10. Ameliorative Effect of Chrysin on Adenine-Induced Chronic Kidney Disease in Rats

    PubMed Central

    Ali, Badreldin H.; Adham, Sirin A.; Al Za’abi, Mohammed; Waly, Mostafa I.; Yasin, Javed; Nemmar, Abderrahim; Schupp, Nicole

    2015-01-01

    Chrysin (5, 7- dihydroxyflavone) is a flavonoid with several pharmacological properties that include antioxidant, anti-inflammatory and antiapoptotic activities. in this work, we investigated some effects of three graded oral doses of chrysin (10, 50 and 250 mg/kg) on kidney structure and function in rats with experimental chronic renal disease (CKD) induced by adenine (0.25% w/w in feed for 35 days), which is known to involve inflammation and oxidative stress. Using several indices in plasma, urine and kidney homogenates, adenine was found to impair kidney function as it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and N-Acetyl-beta-D-glucosaminidase activity. Furthermore, it raised plasma concentrations of the uremic toxin indoxyl sulfate, some inflammatory cytokines and urinary albumin concentration. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine – induced actions were moderately and dose -dependently mitigated by chrysin, especially at the highest dose. Chrysin did not cause any overt adverse effect on the treated rats. The results suggest that different doses of chrysin produce variable salutary effects against adenine-induced CKD in rats, and that, pending further pharmacological and toxicological studies, its usability as a possible ameliorative agent in human CKD should be considered. PMID:25909514

  11. Ameliorative effect of chrysin on adenine-induced chronic kidney disease in rats.

    PubMed

    Ali, Badreldin H; Adham, Sirin A; Al Za'abi, Mohammed; Waly, Mostafa I; Yasin, Javed; Nemmar, Abderrahim; Schupp, Nicole

    2015-01-01

    Chrysin (5, 7- dihydroxyflavone) is a flavonoid with several pharmacological properties that include antioxidant, anti-inflammatory and antiapoptotic activities. in this work, we investigated some effects of three graded oral doses of chrysin (10, 50 and 250 mg/kg) on kidney structure and function in rats with experimental chronic renal disease (CKD) induced by adenine (0.25% w/w in feed for 35 days), which is known to involve inflammation and oxidative stress. Using several indices in plasma, urine and kidney homogenates, adenine was found to impair kidney function as it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and N-Acetyl-beta-D-glucosaminidase activity. Furthermore, it raised plasma concentrations of the uremic toxin indoxyl sulfate, some inflammatory cytokines and urinary albumin concentration. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine - induced actions were moderately and dose -dependently mitigated by chrysin, especially at the highest dose. Chrysin did not cause any overt adverse effect on the treated rats. The results suggest that different doses of chrysin produce variable salutary effects against adenine-induced CKD in rats, and that, pending further pharmacological and toxicological studies, its usability as a possible ameliorative agent in human CKD should be considered.

  12. Protective effects of thymoquinone against apoptosis and oxidative stress by arsenic in rat kidney.

    PubMed

    Sener, Umit; Uygur, Ramazan; Aktas, Cevat; Uygur, Emine; Erboga, Mustafa; Balkas, Gulseren; Caglar, Veli; Kumral, Bahadir; Gurel, Ahmet; Erdogan, Hasan

    2016-01-01

    We aimed to investigate the protective role of thymoquinone (TQ) by targeting its antiapoptotic and antioxidant properties against kidney damage induced by arsenic in rats. We have used the 24 male Sprague-Dawley rats. Rats were divided into three groups. Physiological serum in 10 mL/kg dose as intragastric was given to the control group. Sodium arsenite (10 mg/kg, intragastric by gavage for fifteen days) was given to the arsenic group. Sodium arsenite (10 mg/kg, intragastric by gavage for fifteen days) and TQ (10 mg/kg, intragastric by gavage for 15 days) was given to the arsenic + TQ group. After 15 days, the animals' kidneys were taken theirs, then we have performed histological and apoptotic assessment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) enzyme activities and malondialdehyde (MDA) levels have examined as the oxidative stress parameters. We have determined the levels of arsenic. Increased renal injury and apoptotic cells have been detected in the arsenic group. Degenerative changes in the arsenic + TQ group were diminished. Although the MDA levels were augmented in the arsenic group, SOD, CAT and GSH-Px enzyme activities were lessened than the other groups. Our findings suggest that TQ may impede the oxidative stress, the cells have been damaged and also the generation of apoptotic cells arisen from arsenic. TQ plays a protective role against arsenic-induced toxicity in kidney and may potentially be used as a remedial agent.

  13. Hypertension, kidney disease, HIV and antiretroviral therapy among Tanzanian adults: a cross-sectional study.

    PubMed

    Peck, Robert N; Shedafa, Rehema; Kalluvya, Samuel; Downs, Jennifer A; Todd, Jim; Suthanthiran, Manikkam; Fitzgerald, Daniel W; Kataraihya, Johannes B

    2014-07-29

    The epidemics of HIV and hypertension are converging in sub-Saharan Africa. Due to antiretroviral therapy (ART), more HIV-infected adults are living longer and gaining weight, putting them at greater risk for hypertension and kidney disease. The relationship between hypertension, kidney disease and long-term ART among African adults, though, remains poorly defined. Therefore, we determined the prevalences of hypertension and kidney disease in HIV-infected adults (ART-naive and on ART >2 years) compared to HIV-negative adults. We hypothesized that there would be a higher hypertension prevalence among HIV-infected adults on ART, even after adjusting for age and adiposity. In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years old) attending an HIV clinic in Tanzania were enrolled in three groups: 1) HIV-negative controls, 2) HIV-infected, ART-naive, and 3) HIV-infected on ART for >2 years. The main study outcomes were hypertension and kidney disease (both defined by international guidelines). We compared hypertension prevalence between each HIV group versus the control group by Fisher's exact test. Logistic regression was used to determine if differences in hypertension prevalence were fully explained by confounding. Among HIV-negative adults, 25/153 (16.3%) had hypertension (similar to recent community survey data). HIV-infected adults on ART had a higher prevalence of hypertension (43/150 (28.7%), P = 0.01) and a higher odds of hypertension even after adjustment (odds ratio (OR) = 2.19 (1.18 to 4.05), P = 0.01 in the best model). HIV-infected, ART-naive adults had a lower prevalence of hypertension (8/151 (5.3%), P = 0.003) and a lower odds of hypertension after adjustment (OR= 0.35 (0.15 to 0.84), P = 0.02 in the best model). Awareness of hypertension was ≤ 25% among hypertensive adults in all three groups. Kidney disease was common in all three groups (25.6% to 41.3%) and strongly associated with

  14. Iron-restricted pair-feeding affects renal damage in rats with chronic kidney disease

    PubMed Central

    Naito, Yoshiro; Senchi, Aya; Sawada, Hisashi; Oboshi, Makiko; Horimatsu, Tetsuo; Okuno, Keisuke; Yasumura, Seiki; Ishihara, Masaharu; Masuyama, Tohru

    2017-01-01

    Background We have previously shown that dietary iron restriction prevents the development of renal damage in a rat model of chronic kidney disease (CKD). However, iron deficiency is associated with appetite loss. In addition, calorie restriction is reported to prevent the development of end-stage renal pathology in CKD rats. Thus, the beneficial effect of iron restriction on renal damage may depend on calorie restriction. Here, we investigate the effect of pair-feeding iron restriction on renal damage in a rat model of CKD. Methods First, to determine the amount of food intake, Sprague-Dawley (SD) rats were randomly given an ad libitum normal diet or an iron-restricted diet, and the food intake was measured. Second, CKD was induced by a 5/6 nephrectomy in SD rats, and CKD rats were given either a pair-feeding normal or iron-restricted diet. Results Food intake was reduced in the iron-restricted diet group compared to the normal diet group of SD rats for 16 weeks (mean food intake; normal diet group and iron-restricted diet group: 25 and 20 g/day, respectively). Based on the initial experiments, CKD rats received either a pair-feeding normal or iron-restricted diet (20 g/day) for 16 weeks. Importantly, pair-feeding iron restriction prevented the development of proteinuria, glomerulosclerosis, and tubulointerstitial damage in CKD rats. Interestingly, pair-feeding iron restriction attenuated renal expression of nuclear mineralocorticoid receptor in CKD rats. Conclusions Pair-feeding iron restriction affected renal damage in a rat model of CKD. PMID:28196143

  15. Candesartan augments compensatory changes in medullary transport proteins in the diabetic rat kidney

    PubMed Central

    Blount, Mitsi A.; Sands, Jeff M.; Kent, Kimilia J.; Smith, Tekla D.; Price, S. Russ; Klein, Janet D.

    2008-01-01

    Volume depletion due to persistent glucosuria-induced osmotic diuresis is a significant problem in uncontrolled diabetes mellitus (DM). Angiotensin II receptor blockers (ARBs), such as candesartan, slow the progression of chronic kidney disease in patients with DM. However, mice with genetic knockout of components of the renin-angiotensin system have urine concentrating defects, suggesting that ARBs may exacerbate the volume depletion. Therefore, the effect of candesartan on UT-A1, UT-A3, NKCC2, and aquaporin-2 (AQP2) protein abundances was determined in control and 3-wk DM rats. Aldosterone levels in control rats (0.36 ± 0.06 nM) and candesartan-treated rats (0.34 ± 0.14 nM) were the same. DM rats had higher aldosterone levels (1.48 ± 0.37 nM) that were decreased by candesartan (0.97 ± 0.26 nM). Western analysis showed that UT-A1 expression was increased in DM rats compared with controls in inner medullary (IM) tip (158 ± 13%) and base (120 ± 25%). UT-A3 abundance was increased in IM tip (123 ± 11%) and base (146 ± 17%) of DM rats vs. controls. UT-A3 was unchanged in candesartan-treated control rats. In candesartan-treated DM rats, UT-A3 increased in IM tip (160 ± 14%) and base (210 ± 19%). Candesartan-treated DM rats had slightly higher AQP2 in IM (46%, P < 0.05) vs. control rats. NKCC2/BSC1 was increased 145 ± 10% in outer medulla of DM vs. control rats. We conclude that candesartan augments compensatory changes in medullary transport proteins, reducing the losses of solute and water during uncontrolled DM. These changes may represent a previously unrecognized beneficial effect of type 1 ARBs in DM. PMID:18417538

  16. Uptake of grape anthocyanins into the rat kidney and the involvement of bilitranslocase.

    PubMed

    Vanzo, Andreja; Terdoslavich, Michela; Brandoni, Anabel; Torres, Adriana M; Vrhovsek, Urska; Passamonti, Sabina

    2008-10-01

    Anthocyanins are among the most common flavonoids in the human diet. In spite of their very low bioavailability, anthocyanins are indicated as active in preventing the progress of cardiovascular and neurodegenerative diseases, obesity, inflammation, and cancer. Any piece of knowledge concerning absorption, tissue distribution, metabolism, and excretion of dietary anthocyanins is expected to help understanding the apparent paradox between their low concentrations in cells and their bioactivity. The aim of this work was to investigate the renal uptake of dietary anthocyanins and the underlying molecular mechanism. A solution containing anthocyanins extracted from grape (Vitis vinifera) was introduced into the isolated stomach of anesthetized rats; after both 10 and 30 min, plasma, liver, and kidney were analyzed for their anthocyanin contents. While anthocyanins in the liver were at apparent equilibrium with plasma both after 10 and 30 min, kidney anthocyanins were 3- and 2.3-fold higher than in plasma, after 10 and 30 min, respectively. Since the transport activity of the bilitranslocase in kidney basolateral membrane vesicles was competitively inhibited by malvidin 3-glucoside (K(i) = 4.8 +/- 0.2 microM), the anthocyanin uptake from blood into kidney tubular cells is likely to be mediated by the kidney isoform of this organic anion membrane transporter.

  17. Regulation of elongation factor-1 expression by vitamin E in diabetic rat kidneys.

    PubMed

    Al-Maghrebi, May; Cojocel, Constantin; Thompson, Mary S

    2005-05-01

    Translation elongation factor-1 (EF-1) forms a primary site of regulation of protein synthesis and has been implicated amongst others in tumorigenesis, diabetes and cell death. To investigate whether diabetes-induced oxidative stress affects EF-1 gene expression, we used a free radical scavenger, vitamin E. The following groups of rats (5/group) were studied: control, vitamin E control, diabetic and diabetic treated with vitamin E. Markers of hyperglycemia, kidney function, oxidative stress, and kidney hypertrophy were elevated in diabetic rats. Increased urinary protein excretion indicated early signs of glomerular and tubular dysfunction. The mRNA and protein levels of the three EF-1 subunits (A, Balpha, and Bgamma) were determined in renal cortex extracts using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), northern blot analysis and western blotting. EF-1A mRNA expression in renal cortex extracts was significantly increased by at least 2-fold (p < 0.002) in diabetic rats; however, there was no change in the mRNA levels of EF-1Balpha and EF-1Bgamma subunits. Similar results were observed at the protein level. Treatment of diabetic rats with vitamin E for 10 days suppressed both glycemic and oxidative stresses in renal cortex and kidney hypertrophy. EF-1A mRNA and protein levels were also reduced to control levels. In conclusion, EF-1A but not EF-1Balpha and EF-1Bgamma gene expression is significantly enhanced in the renal cortex of diabetic rats. Normalization of enhanced EF-1A expression by vitamin E treatment suggests a role for EF-1A during diabetes-induced oxidative stress.

  18. Daily Intake of Grape Powder Prevents the Progression of Kidney Disease in Obese Type 2 Diabetic ZSF1 Rats.

    PubMed

    Almomen, Salwa M K; Guan, Qiunong; Liang, Peihe; Yang, Kaidi; Sidiqi, Ahmad M; Levin, Adeera; Du, Caigan

    2017-03-31

    Individuals living with metabolic syndrome (MetS) such as diabetes and obesity are at high risk for developing chronic kidney disease (CKD). This study investigated the beneficial effect of whole grape powder (WGP) diet on MetS-associated CKD. Obese diabetic ZSF1 rats, a kidney disease model with MetS, were fed WGP (5%, w/w) diet for six months. Kidney disease was determined using blood and urine chemical analyses, and histology. When compared to Vehicle controls, WGP intake did not change the rat bodyweight, but lowered their kidney, liver and spleen weight, which were in parallel with the lower serum glucose and the higher albumin or albumin/globin ratio. More importantly, WGP intake improved the renal function as urination and proteinuria decreased, or it prevented kidney tissue damage in these diabetic rats. The renal protection of WGP diet was associated with up-regulation of antioxidants (Dhcr24, Gstk1, Prdx2, Sod2, Gpx1 and Gpx4) and downregulation of Txnip (for ROS production) in the kidneys. Furthermore, addition of grape extract reduced H₂O₂-induced cell death of cultured podocytes. In conclusion, daily intake of WGP reduces the progression of kidney disease in obese diabetic rats, suggesting a protective function of antioxidant-rich grape diet against CKD in the setting of MetS.

  19. Early postnatal ibuprofen and indomethacin effects in suckling and weanling rat kidneys.

    PubMed

    Hasan, Jamal; Beharry, Kay D; Gharraee, Zahra; Stavitsky, Yuri; Abad-Santos, Patricia; Abad-Santos, Matthew; Aranda, Jacob V; Modanlou, Houchang D

    2008-03-01

    The use of indomethacin in preterm newborn infants with symptomatic patent ductus arteriosus is associated with compromised renal function. Ibuprofen has been shown to be as effective as indomethacin with fewer renal side effects. We examined the hypothesis that early postnatal ibuprofen has less adverse effects on neonatal rat renal prostanoids, COX-2 expression, and angiotensin II than indomethacin. Newborn rats received IP injections of human therapeutic doses of ibuprofen or indomethacin on the first 3 days of life. Control rats were treated with equivalent volume saline. Kidneys were assessed in suckling and weanling rats for prostanoids, COX-2 expression, and angiotensin II. In suckling rats, indomethacin suppressed PGE(2) and COX-2 expression, and increased PGF(2alpha), whereas ibuprofen increased COX-2 and angiotensin II. Although both NSAIDs suppressed 6-ketoPGF(1alpha) and TxB(2) levels in suckling rats, the effect was sustained in weanling rats with indomethacin. Our findings demonstrate that indomethacin exhibits more potent suppressive effects on renal COX-2 and vasodilator prostanoids which are important regulators of renal development and function. These long-term, sustained effects may explain in part, why indomethacin exerts more severe adverse renal effects than ibuprofen, when administered during early postnatal life.

  20. Medication safety and chronic kidney disease in older adults prescribed metformin: a cross-sectional analysis

    PubMed Central

    2014-01-01

    Background Medication safety in patients with chronic kidney disease (CKD) is a growing concern. This is particularly relevant in older adults due to underlying CKD. Metformin use is contraindicated in patients with abnormal kidney function; however, many patients are potentially prescribed metformin inappropriately. We evaluated the prevalence of CKD among older adults prescribed metformin for type 2 diabetes mellitus using available equations to estimate kidney function and examined demographic characteristics of patients who were potentially inappropriately prescribed metformin. Methods We conducted a cross-sectional analysis of older adults aged ≥65 years prescribed metformin from March 2008-March 2009 at an urban tertiary-care facility in Seattle, Washington, USA. CKD was defined using National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Creatinine clearance was calculated using the Cockcroft-Gault equation; estimated glomerular filtration rate was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology (EPI) Collaboration equations. Regression analyses were used to determine the associations between demographic characteristics and prevalent CKD. Results Among 356 subjects (median age 69 years, 52.5% female, 39.4% non-Hispanic black), prevalence of stage 3 or greater CKD calculated by any of the equations was 31.4%. The Cockcroft-Gault equation identified more subjects as having CKD (23.7%) than the abbreviated MDRD (21.1%) or CKD-EPI (21.7%) equations (P < 0.001). Older age (OR = 1.13, 95% CI 1.08-1.19) and female sex (OR = 2.51, 95% CI 1.44-4.38) were associated with increased odds of potentially inappropriate metformin prescription due to CKD; non-Hispanic black race was associated with decreased odds of potentially inappropriate metformin prescription due to CKD (OR = 0.41, 95% CI 0.23-0.71). Conclusions CKD is common in older adults prescribed metformin for type 2

  1. Effect of bumetanide, frusemide and prostaglandin E2 on the isolated perfused kidney of rat and rabbit.

    PubMed Central

    Foy, J. M.; Nuhu, S. Z.

    1984-01-01

    Rat and rabbit kidneys were isolated, perfused via the renal artery with Krebs solution and perfusion pressure monitored. Dose-response curves to noradrenaline administered as bolus doses or frequency-response curves from transmural arterial electrical stimulation were obtained. A 1 h continuous infusion of bumetanide (0.1 micrograms ml-1) increased the sensitivity of rat kidney vessels to noradrenaline, an effect also seen when bumetanide and flurbiprofen (6 micrograms ml-1) were simultaneously perfused. In the rabbit there was a decreased sensitivity to both electrical stimulation and noradrenaline. A 1 h continuous infusion of frusemide (6 micrograms ml-1) only altered the effects of electrical stimulation. An increased sensitivity in the rat (abolished by flurbiprofen) and a decreased sensitivity in the rabbit kidney was observed. A 1 h continuous infusion of prostaglandin (PG)E2 (2 ng ml-1) increased the sensitivity of rat kidney to both types of stimuli but caused a reduction in the responsiveness of the rabbit kidney to electrical stimuli only. Addition of flurbiprofen only slightly modified these results. The results emphasize and confirm the fundamental difference in reactivity of the rat and rabbit kidney. Bumetanide and frusemide, two ostensibly similar loop diuretics, show significantly different effects on these preparations suggesting that any modification by non-steroidal anti-inflammatory drugs cannot wholly be explained by similar PGE2 induced haemodynamic changes. PMID:6587927

  2. Effects of lovastatin treatment on the metabolic distributions in the Han:SPRD rat model of polycystic kidney disease.

    PubMed

    Klawitter, Jelena; Zafar, Iram; Klawitter, Jost; Pennington, Alexander T; Klepacki, Jacek; Gitomer, Berenice Y; Schrier, Robert W; Christians, Uwe; Edelstein, Charles L

    2013-07-31

    We previously demonstrated that lovastatin decreases cyst volume and improves kidney function in the Han:SPRD (Cy/+) rat model of ADPKD. Since endothelial dysfunction and inflammatory activity are evident in patients with ADPKD, we investigated whether lovastatin reduces the inflammation and vascular dysfunction and improves kidney cell energy metabolism of Cy/+ rats. Cy/+ and normal littermate control animals (+/+) were treated with either lovastatin (4 mg/kg/day) or vehicle (ethanol) from 3-8 weeks of age. 1H-NMR analysis was performed on water-soluble and lipid kidney fractions following perchloric acid extraction. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to assess endothelial dysfunction, oxidative stress and inflammation markers in plasma and kidney tissue extracts. Cy/+ rats showed perturbations in fatty acid metabolism and increased synthesis of pro-inflammatory lipoxygenases-produced bioactive lipids was observed. Lovastatin decreased inflammatory markers, specifically 13-HODE, 12-HETE and leukotriene B4. In Cy/+ rats, lovastatin reduced the elevated homocysteine and allantoin plasma levels and increased arginine, that is known to positively affect NO production. As previously described, lovastatin was able to decrease kidney weight and cyst volume density in Cy/+ rats. The decrease in cyst volume was accompanied by a reduction in arachidonic acid-mediated inflammation markers, the normalization of metabolism of NO precursors and the improvement of kidney energy cell metabolism.

  3. Antioxidant effects of damiana (Turnera diffusa Willd. ex Schult.) in kidney mitochondria from streptozotocin-diabetic rats.

    PubMed

    Edgar Romualdo, Esquivel-Gutiérrez; Lilia, Alcaraz-Meléndez; Rafael, Salgado-Garciglia; Alfredo, Saavedra-Molina

    2017-09-26

    The antioxidant effects of water-ethanol extract (WEE) from Turnera diffusa (damiana) in kidney mitochondria from experimental streptozotocin-induced diabetes mellitus (STZ-DM) rats was evaluated. STZ-DM rats were orally treated during three and five weeks. After experimental periods, kidney mitochondria were isolated and malondialdehyde (MDA), nitric oxide (NO•) and protein nitrosylation levels were measured. Also, blood glucose (BG) and body weight (BW) were recorded. Damiana significantly reduced the MDA and NO• levels in kidney mitochondria, although no changes in protein nitrosylation were observed and it did not have the potential to reverse the hyperglycaemia. In conclusion, WEE of T. diffusa have antioxidant properties that may prevent damage induced by mitochondrial oxidative stress in kidneys of STZ-DM rats.

  4. Sodium regulation of angiotensinogen mRNA expression in rat kidney cortex and medulla.

    PubMed Central

    Ingelfinger, J R; Pratt, R E; Ellison, K; Dzau, V J

    1986-01-01

    Rat liver angiotensinogen cDNA (pRang 3) and mouse renin cDNA (pDD-1D2) were used to identify angiotensinogen and renin mRNA sequences in rat kidney cortex and medulla in rats on high and low salt diet. Angiotensinogen mRNA sequences were present in renal cortex and medulla in apparently equal proportions, whereas renin mRNA sequences were found primarily in renal cortex. Average relative signal of rat liver to whole kidney angiotensinogen mRNA was 100:3. Densitometric analysis of Northern blots demonstrated that renal cortical angiotensinogen mRNA concentrations increased 3.5-fold (P less than 0.001) and medulla, 1.5-fold (P less than 0.005) on low sodium compared with high sodium diet, whereas renal cortex renin mRNA levels increased 6.8-fold (P less than 0.0005). Dietary sodium did not significantly influence liver angiotensinogen mRNA levels. These findings provide evidence for sodium regulation of renal renin and angiotensinogen mRNA expressions, which supports potential existence of an intrarenally regulated RAS and suggest that different factors regulate renal and hepatic angiotensinogen. Images PMID:3533999

  5. Effect of diesel exhaust particles on renal vascular responses in rats with chronic kidney disease.

    PubMed

    Al Suleimani, Y M; Al Mahruqi, A S; Al Za'abi, M; Shalaby, A; Ashique, M; Nemmar, A; Ali, B H

    2017-02-01

    Several recent studies have indicated the possible association between exposure to particulate air pollution and the increased rate of morbidity and mortality in patients with kidney diseases. The link of this observation to vascular damage has not been adequately addressed. Therefore, this study aims to investigate possible vascular damage that might be associated with exposure to diesel exhaust particles (DP) in adenine (AD)-induced chronic kidney disease (CKD) in rats, and the possible ameliorative effect of gum acacia (GA). CKD was induced by feeding AD (0.75%, w/w), and DP (0.5 mg/kg) was instilled intratracheally every second day and GA was given concomitantly in the drinking water at a dose of 15% w/v. All treatments were given concomitantly for 28 days. Changes in renal blood flow (RBF) and systolic and diastolic blood pressure were monitored in these animals after anesthesia, together with several other endpoints. Exposure to DP significantly reduced RBF and this was significantly potentiated in AD-treated rats. Phenylephrine-induced decreases in RBF and increases in systolic and diastolic blood pressure were severely potentiated in rats exposed to DP, and these actions were significantly augmented in AD-treated rats. GA did not significantly affect the vascular impairment induced by AD and DP given together. This study provides experimental evidence that exposure to particulate air pollution can exacerbate the vascular damage seen in patients with CKD. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 541-549, 2017.

  6. Mouse stem cells seeded into decellularized rat kidney scaffolds endothelialize and remodel basement membranes

    PubMed Central

    Ross, Edward A.; Abrahamson, Dale R.; St. John, Patricia; Clapp, William L.; Williams, Matthew J.; Terada, Naohiro; Hamazaki, Takashi; Ellison, Gary W.; Batich, Christopher D.

    2012-01-01

    Introduction To address transplant organ shortage, a promising strategy is to decellularize kidneys in a manner that the scaffold retains signals for seeded pluripotent precursor cells to differentiate and recapitulate native structures: matrix-to-cell signaling followed by cell-cell and cell-matrix interactions, thereby remodeling and replacing the original matrix. This would reduce scaffold antigenicity and enable xeno-allografts. Results DAPI-labeled cells in arterial vessels and glomeruli were positive for both endothelial lineage markers, BsLB4 and VEGFR2. Rat scaffold’s basement membrane demonstrated immunolabeling with anti-mouse laminin β1. Labeling intensified over time with 14 day incubations. Conclusion We provide new evidence for matrix-to-cell signaling in acellular whole organ scaffolds that induces differentiation of pluripotent precursor cells to endothelial lineage. Production of mouse basement membrane supports remodeling of host (rat)-derived scaffolds and thereby warrants further investigation as a promising approach for xenotransplantation. Methods We previously showed that murine embryonic stem cells arterially seeded into acellular rat whole kidney scaffolds multiply and demonstrate morphologic, immunohistochemical and gene expression evidence for differentiation. Vascular cell endothelialization was now further tested by endothelial specific BsLB4 lectin and anti-VEGFR2 (Flk1) antibodies. Remodeling of the matrix basement membranes from rat to mouse (“murinization”) was assessed by a monoclonal antibody specific for mouse laminin β1 chain. PMID:22692231

  7. Angiotensin 2 type 1 receptor blockade different affects postishemic kidney injury in normotensive and hypertensive rats.

    PubMed

    Miloradović, Zoran; Ivanov, Milan; Jovović, Đurđica; Karanović, Danijela; Vajić, Una Jovana; Marković-Lipkovski, Jasmina; Mihailović-Stanojević, Nevena; Milanović, Jelica Grujić

    2016-12-01

    Many studies demonstrated that angiotensin 2 type 1 receptor (AT1R) blockade accelerates renal recovery in post-ischaemic kidney but there are many controversies related to its net effect on kidney structure and function. During the past years, our research group was trying to define the pathophysiological significance of the renin-angiotensin system on post-ischemic acute renal failure (ARF) development in normotensive Wistar as well as hypertensive rats (SHR). This review mostly summarizes our experience in that field. Our previous studies in normotensive rats revealed that AT1R blockade, except slightly renal vascular resistance improvement, had no other obvious beneficial effects, and therefore implies angiotensin 2 (Ang-2) overexpression as non-dominant on kidney reperfusion injuries development. Similarly it was observed in Wistar rats with induced mild (L-NAME, 3 mg/kg b.w.) nitric oxide (NO) deficiency. Expectably, in strong induced (L-NAME, 10 mg/kg b.w.) NO deficiency associated with ARF, massive tubular injuries indicate harmful effects of AT1R blockade, implying strongly disturbed glomerular filtration and suggesting special precaution related to AT1R blockers usage. Opposite to previous, by our opinion, AT1R antagonism promises new advance in treatment of essentially hypertensive subjects who develop ARF. Increased glomerular filtration, diminished oxidative stress, and most importantly improved tubular structure in postishemic SHR treated with AT1R blocker losartan, implicate Ang-2 over production as potently agent in the kidney ischemic injury, partly trough generation of reactive oxygen species. These data contribute understanding the pathogenesis of this devastating illness in hypertensive surroundings.

  8. An observational study of health literacy and medication adherence in adult kidney transplant recipients

    PubMed Central

    Demian, Maryam N.; Shapiro, R. Jean

    2016-01-01

    Background There is a high prevalence of non-adherence to immunosuppressants in kidney transplant recipients. Although limited health literacy is common in kidney recipients and is linked to adverse outcomes in other medical populations, its effect on medication adherence in kidney transplant recipients remains poorly understood. The objective was to investigate the effect of lower health literacy on immunosuppressant adherence. Methods Kidney recipients who were at least 6 months post-transplant and outpatients of Vancouver General Hospital in B.C., Canada were recruited through invitation letters. A total of 96 recipients completed the Health Literacy Questionnaire, which provides a multifactorial profile of self-reported health literacy and the Transplant Effects Questionnaire-Adherence subscale measuring self-reported immunosuppressant adherence. Hierarchical linear regression was used to analyze the association between health literacy and adherence after controlling for identified risk factors of non-adherence. Results Our sample was on average 53 years old, 56% male and 9 years post-transplant. Kidney recipients reported low levels of health literacy on scales measuring active health management and critical appraisal of information and 75% reported non-perfect adherence. Worse adherence was associated with poorer overall health literacy (ΔR2 = 0.08, P = 0.004) and lower scores on six of nine of the health literacy factors. Conclusions Poorer health literacy is associated with lower immunosuppressant adherence in adult kidney transplant recipients suggesting the importance of considering a recipient's level of health literacy in research and clinical contexts. Medication adherence interventions can target the six factors of health literacy identified as being risk factors for lower medication adherence. PMID:27994867

  9. An observational study of health literacy and medication adherence in adult kidney transplant recipients.

    PubMed

    Demian, Maryam N; Shapiro, R Jean; Thornton, Wendy Loken

    2016-12-01

    There is a high prevalence of non-adherence to immunosuppressants in kidney transplant recipients. Although limited health literacy is common in kidney recipients and is linked to adverse outcomes in other medical populations, its effect on medication adherence in kidney transplant recipients remains poorly understood. The objective was to investigate the effect of lower health literacy on immunosuppressant adherence. Kidney recipients who were at least 6 months post-transplant and outpatients of Vancouver General Hospital in B.C., Canada were recruited through invitation letters. A total of 96 recipients completed the Health Literacy Questionnaire, which provides a multifactorial profile of self-reported health literacy and the Transplant Effects Questionnaire-Adherence subscale measuring self-reported immunosuppressant adherence. Hierarchical linear regression was used to analyze the association between health literacy and adherence after controlling for identified risk factors of non-adherence. Our sample was on average 53 years old, 56% male and 9 years post-transplant. Kidney recipients reported low levels of health literacy on scales measuring active health management and critical appraisal of information and 75% reported non-perfect adherence. Worse adherence was associated with poorer overall health literacy (ΔR(2) = 0.08, P = 0.004) and lower scores on six of nine of the health literacy factors. Poorer health literacy is associated with lower immunosuppressant adherence in adult kidney transplant recipients suggesting the importance of considering a recipient's level of health literacy in research and clinical contexts. Medication adherence interventions can target the six factors of health literacy identified as being risk factors for lower medication adherence.

  10. Effect of TCDD on ACARAT activity and vitamin A accumulation in the kidney of male Sprague-Dawley rats

    SciTech Connect

    Jurek, M.A.; Powers, R.H.; Gilbert, L.C.; Aust, S.D.

    1987-05-01

    Previous studies have shown that rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit symptoms of vitamin A deficiency, including hypophagia, failure of normal growth, loss of hepatic vitamin A and accumulation of vitamin A in the kidney. They observed that male Sprague-Dawley rats treated with a single dose of TCDD gained less weight than control rats over a 12 day period. Treated rats showed a progressive loss of hepatic retinyl esters to levels 55% that of control rats. Treated rats accumulated renal vitamin A, with retinyl palmitate levels reaching 5.2x that of control animals, while retinol levels were elevated to 1.5x that of control rats. The ratio of retinyl palmitate to retinol was significantly greater in treated rats than in the control rats. Acyl CoA:Retinol Acyl Transferase (ACARART) activity was 2x greater in kidneys from treated rats, and positively correlated with retinyl palmitate concentrations. They suggest that accumulation of retinyl esters in the kidney occurs as a result of retinol esterification, in response to the TCDD-induced vitamin A deficiency.

  11. Jejunal ultrastructural changes induced by kidney bean (Phaseolus vulgaris) lectins in rats.

    PubMed Central

    Rossi, M. A.; Mancini Filho, J.; Lajolo, F. M.

    1984-01-01

    Rats maintained for a period of 5 days on a diet containing purified lectins extracted from a Brazilian variety (called 'Jalo') of white kidney beans (Phaseolus vulgaris) developed marked ultrastructural changes in the epithelium of the proximal jejunum, while both pair-fed and ad-libitum-fed controls did not. The jejunal absorptive cells of rats fed a diet containing lectins exhibited conspicuous abnormalities of the microvilli. They were shorter, slightly thicker, irregular and more sparse; some were bi- or tri-furcated, sharing a common base of implantation. A slightly disorganized terminal web was present below the brush border. The supranuclear cytoplasm of a great number of cells exhibited large cytolysosomes. Comparison with the results of pair-feeding suggests that purified bean lectins have a direct causative role in the pathogenesis of absorptive cell changes in the jejunal villi of rats. The possible pathogenic mechanism of these lesions is discussed. Images Fig. 1 Fig. 2 Fig. 3 PMID:6696828

  12. Water and exchangeable sodium in Goldblatt two-kidney, two-clip hypertensive rats

    SciTech Connect

    Mac Cormack, W.P.; Roson, M.I.; Maquieira, M.K.; Mendez, M.A.; Santoro, F.M.; Morera, S.; de la Riva, I.J.

    1986-01-01

    Exchangeable /sup 22/Na (ExNa), total body water (TBW) and the inulin space (InSp) were determined in two-kidney, two-clip (2K-2C) hypertensive and sham operated (normotensive) control rats 6-8 weeks after surgery. TBW (ml/kg lean body weight) was the same in hypertensive and sham rats. In contrast, ExNa (mEq/kglbw) and InSp (ml/kglbw) significantly increased (p less than 0.01) in rats whose hypertension did not exceed 170 mmHg. Consequently, sham, moderate hypertensive (less than 170 mmHg) and severe hypertensive (less than 170 mmHg) animals showed equal TBW but differed in body water distribution in that moderately hypertensive animals displayed a redistribution of water in favor of the extracellular space.

  13. Jejunal ultrastructural changes induced by kidney bean (Phaseolus vulgaris) lectins in rats.

    PubMed

    Rossi, M A; Mancini Filho, J; Lajolo, F M

    1984-02-01

    Rats maintained for a period of 5 days on a diet containing purified lectins extracted from a Brazilian variety (called 'Jalo') of white kidney beans (Phaseolus vulgaris) developed marked ultrastructural changes in the epithelium of the proximal jejunum, while both pair-fed and ad-libitum-fed controls did not. The jejunal absorptive cells of rats fed a diet containing lectins exhibited conspicuous abnormalities of the microvilli. They were shorter, slightly thicker, irregular and more sparse; some were bi- or tri-furcated, sharing a common base of implantation. A slightly disorganized terminal web was present below the brush border. The supranuclear cytoplasm of a great number of cells exhibited large cytolysosomes. Comparison with the results of pair-feeding suggests that purified bean lectins have a direct causative role in the pathogenesis of absorptive cell changes in the jejunal villi of rats. The possible pathogenic mechanism of these lesions is discussed.

  14. Reactive oxygen species mediate compensatory glomerular hypertrophy in rat uninephrectomized kidney.

    PubMed

    Ozeki, Masahito; Nagasu, Hajime; Satoh, Minoru; Namikoshi, Tamehachi; Haruna, Yoshisuke; Tomita, Naruya; Sasaki, Tamaki; Kashihara, Naoki

    2009-09-01

    Hyperfiltration in glomeruli is the most common pathway to progressive renal dysfunction. Moreover, reduction of renal mass by unilateral nephrectomy results in an immediate increase in glomerular flow to the remnant kidney, followed by compensatory glomerular hypertrophy. Reactive oxygen species (ROS) are involved in renal hypertrophic responses; however, the role of ROS in compensatory glomerular hypertrophy remains unclear. Therefore, this role was investigated in the present study. Wistar rats were randomly placed into two groups: uninephrectomized rats (Nx) and uninephrectomized rats treated with tempol (Nx + TP). The glomerular volume increased in the Nx 1 week after surgery, but was significantly suppressed in the Nx + TP. Levels of phospho-Akt and phospho-ribosomal protein S6, which are critical for cell growth and hypertrophy, were markedly increased in the glomeruli of the Nx, while tempol treatment almost abolished the activation of these proteins. These results suggest that ROS have important roles in compensatory hypertrophy in glomeruli.

  15. Donor preconditioning with a calcineurin inhibitor improves outcome in rat syngeneic kidney transplantation.

    PubMed

    Shihab, Fuad S; Bennett, William M; Andoh, Takeshi F

    2009-02-15

    Ischemia-reperfusion injury (IRI) in the early posttransplant period affects immediate graft function and late allograft dysfunction. This study determines the influence of pharmacologic preconditioning with a calcineurin inhibitor on IRI in a syngeneic F344 rat kidney transplant model. Donor rats were pretreated with one dose of cyclosporine (10 mg/kg) or tacrolimus (1 mg/kg) administered at 24 hr or 7 days before being subjected to 2 hr of cold ischemia and then transplanted. Pharmacologic preconditioning significantly improved renal function, as assessed by serum creatinine and inulin clearance, and histologic score versus vehicle-treated rats. There were no differences between cyclosporine and tacrolimus in the measured outcomes. This renoprotective effect, although not complete, was seen with only one dose of calcineurin inhibitor, and the effect was sustained for at least 7 days before IRI. This approach may represent a viable pharmacologic intervention to decrease IRI at the time of organ transplantation.

  16. Inflammatory Kidney and Liver Tissue Response to Different Hydroxyethylstarch (HES) Preparations in a Rat Model of Early Sepsis

    PubMed Central

    Schimmer, Ralph C.; Urner, Martin; Voigtsberger, Stefanie; Booy, Christa; Roth Z’Graggen, Birgit; Beck-Schimmer, Beatrice; Schläpfer, Martin

    2016-01-01

    Background Tissue hypoperfusion and inflammation in sepsis can lead to organ failure including kidney and liver. In sepsis, mortality of acute kidney injury increases by more than 50%. Which type of volume replacement should be used is still an ongoing debate. We investigated the effect of different volume strategies on inflammatory mediators in kidney and liver in an early sepsis model. Material and Methods Adult male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP) and assigned to three fluid replenishment groups. Animals received 30mL/kg of Ringer’s lactate (RL) for 2h, thereafter RL (75mL/kg), hydroxyethyl starch (HES) balanced (25mL/kg), containing malate and acetate, or HES saline (25mL/kg) for another 2h. Kidney and liver tissue was assessed for inflammation. In vitro rat endothelial cells were exposed to RL, HES balanced or HES saline for 2h, followed by stimulation with tumor necrosis factor-α (TNF-α) for another 4h. Alternatively, cells were exposed to malate, acetate or a mixture of malate and acetate, reflecting the according concentration of these substances in HES balanced. Pro-inflammatory cytokines were determined in cell supernatants. Results Cytokine mRNA in kidney and liver was increased in CLP animals treated with HES balanced compared to RL, but not after application of HES saline. MCP-1 was 3.5fold (95% CI: 1.3, 5.6) (p<0.01) and TNF-α 2.3fold (95% CI: 1.2, 3.3) (p<0.001) upregulated in the kidney. Corresponding results were seen in liver tissue. TNF-α-stimulated endothelial cells co-exposed to RL expressed 3529±1040pg/mL MCP-1 and 59±23pg/mL CINC-1 protein. These cytokines increased by 2358pg/mL (95% CI: 1511, 3204) (p<0.001) and 29pg/ml (95% CI: 14, 45) (p<0.01) respectively when exposed to HES balanced instead. However, no further upregulation was observed with HES saline. PBS supplemented with acetate increased MCP-1 by 1325pg/mL (95% CI: 741, 1909) (p<0.001) and CINC-1 by 24pg/mL (95% CI: 9, 38) (p<0

  17. Protective effects of propofol on endotoxemia-induced acute kidney injury in rats.

    PubMed

    Cui, Wen-Yao; Tian, A-Yong; Bai, Tao

    2011-11-01

    1. Animal studies suggest that propofol protects against endotoxaemia-induced lung and kidney injury. Upregulation of aquaporin expression in lung tissue mediates these effects, but the mechanism of action in the kidney is unclear. The present study examined the protective effects of propofol on endotoxaemia-induced acute kidney injury in rats. 2. A rat model of endotoxaemia was established using lipopolysaccharide (LPS). We determined the effects of 10% propofol administration 1 h before, during and 1 h after LPS-induced endotoxaemia on expression of aquaporin (AQP)-2, tumour necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, caspase 3, Bcl-2 and Bax using reverse transcription-polymerase chain reaction, western blotting and immunocytochemistry. Renal morphology, superstructure, apoptosis and function were also assessed. 3. Normal renal tubular structure was seen in the propofol pretreated group, but LPS treatment resulted in changes to renal tissue morphology. Propofol treatment improved renal function in LPS-treated rats. Pretreatment with propofol 1 h before LPS normalized urine and serum osmolality, serum creatinine and blood urea nitrogen to control levels. Lipopolysaccharide downregulated expression of AQP-2 and downregulated the expression of ICAM-1 and TNF-α. These effects were reversed by propofol treatment. Lipopolysaccharide reduced the Bcl2 : Bax ratio and induced renal cell apoptosis and these effects were reduced by propofol treatment. Overall, propofol pretreatment had greater effects than concurrent treatment or propofol administration after LPS induction of endotoxaemia. 4. In conclusion, propofol pretreatment protected renal function in a rat model of endotoxaemia. Further studies are necessary to confirm this effect in other experimental models and in humans.

  18. Effect of thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat kidney

    PubMed Central

    Altuner, Durdu; Cetin, Nihal; Suleyman, Bahadir; Aslan, Zeynep; Hacimuftuoglu, Ahmet; Gulaboglu, Mine; Isaoglu, Neslihan; Demiryilmaz, Ismail; Suleyman, Halis

    2013-01-01

    Objectives: The biochemical effects of thiamine pyrophosphate on ischemia-reperfusion (IR) induced oxidative damage and DNA mutation in rat kidney tissue were investigated, and compared to thiamine. Materials and Methods: Rats were divided into four groups: Renal ischemia-reperfusion (RIR); thiamine pyrophosphate + RIR (TPRIR); thiamine + RIR (TRIR); and sham group (SG). Results: The results of biochemical experiments have shown that malondialdehyde (MDA) levels in rat kidney tissue after TRIR and TPRIR treatment were 7.2 ± 0.5 (P > 0.05) and 3.3 ± 0.3 (P < 0.0001) μmol/g protein, respectively. The MDA levels in the SG rat kidney tissue and in RIR group were 3.6 ± 0.2 (P < 0.0001) and 7.6 ± 0.6 μmol/g protein, respectively. Total glutathione (tGSH) levels in TRIR, TPRIR, SG, and RIR animal groups were 2.2 ± 0.3 (P > 0.05), 5.8 ± 0.4 (P < 0.0001), 6.2 ± 0.2 (P < 0.0001), and 1.7 ± 0.2 nmol/g protein, respectively. In the TRIR, TPRIR, SG, and RIR animal groups; 8-hydroxyguanine (8-OHGua)/Gua levels, which indicate mutagenic DNA, were 1.75 ± 0.12 (P > 0.05), 0.93 ± 0.1 (P < 0.0001), 0.85 ± 0.08 (P < 0.0001), and 1.93 ± 0.24 pmol/L, respectively. Conclusions: It has been shown that thiamine pyrophosphate prevents increase in mutagenic DNA in IR induced oxidative damage, whereas thiamine does not have this effect. PMID:24014907

  19. Comparative expression of the extracellular calcium-sensing receptor in the mouse, rat, and human kidney.

    PubMed

    Graca, J A Z; Schepelmann, M; Brennan, S C; Reens, J; Chang, W; Yan, P; Toka, H; Riccardi, D; Price, S A

    2016-03-15

    The calcium-sensing receptor (CaSR) was cloned over 20 years ago and functionally demonstrated to regulate circulating levels of parathyroid hormone by maintaining physiological serum ionized calcium concentration ([Ca(2+)]). The receptor is highly expressed in the kidney; however, intrarenal and intraspecies distribution remains controversial. Recently, additional functions of the CaSR receptor in the kidney have emerged, including parathyroid hormone-independent effects. It is therefore critical to establish unequivocally the localization of the CaSR in the kidney to relate this to its proposed physiological roles. In this study, we determined CaSR expression in mouse, rat, and human kidneys using in situ hybridization, immunohistochemistry (using 8 different commercially available and custom-made antibodies), and proximity ligation assays. Negative results in mice with kidney-specific CaSR ablation confirmed the specificity of the immunohistochemistry signal. Both in situ hybridization and immunohistochemistry showed CaSR expression in the thick ascending limb, distal tubule, and collecting duct of all species, with the thick ascending limb showing the highest levels. Within the collecting ducts, there was significant heterogeneity of expression between cell types. In the proximal tubule, lower levels of immunoreactivity were detected by immunohistochemistry and proximity ligation assays. Proximity ligation assays were the only technique to demonstrate expression within glomeruli. This study demonstrated CaSR expression throughout the kidney with minimal discrepancy between species but with significant variation in the levels of expression between cell and tubule types. These findings clarify the intrarenal distribution of the CaSR and enable elucidation of the full physiological roles of the receptor within this organ.

  20. Pyrimethamine inhibits adult polycystic kidney disease by modulating STAT signaling pathways

    PubMed Central

    Takakura, Ayumi; Nelson, Erik A.; Haque, Nadeem; Humphreys, Benjamin D.; Zandi-Nejad, Kambiz; Frank, David A.; Zhou, Jing

    2011-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited disorder mostly caused by mutations in PKD1, encoding polycystin-1 (PC1). The disease is characterized by development and growth of epithelium-lined cyst in both kidneys, often leading to renal failure. There is no specific treatment for this disease. Here, we report a sustained activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) in ischemic injured and uninjured Pkd1 knockout polycystic kidneys and in human ADPKD kidneys. Through a chemical library screen, we identified the anti-parasitic compound pyrimethamine as an inhibitor of STAT3 function. Treatment with pyrimethamine decreases cell proliferation in human ADPKD cells and blocks renal cyst formation in an adult and a neonatal PKD mouse model. Moreover, we demonstrated that a specific STAT3 inhibitor, S3I-201, reduces cyst formation and growth in a neonatal PKD mouse model. Our results suggest that PC1 acts as a negative regulator of STAT3 and that blocking STAT3 signaling with pyrimethamine or similar drugs may be an attractive therapy for human ADPKD. PMID:21821671

  1. Chronic caffeine consumption exacerbates hypertension in rats with polycystic kidney disease.

    PubMed

    Tanner, G A; Tanner, J A

    2001-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder frequently associated with renal failure, hypertension, and other abnormalities. The present study determined whether chronic caffeine intake in an animal model of this disease would affect renal structure and function and blood pressure. Heterozygous male Han:Sprague-Dawley rats with ADPKD and normal littermates were provided with either tap water or solutions of caffeine to drink, starting at 1 month of age. When rats were aged 6 months, glomerular filtration rate (GFR) and mean arterial blood pressure (MAP) were measured under Inactin (Byk Gulden, Konstanz, Germany) anesthesia. Caffeine intake had no effect on GFR or cyst development in rats with PKD. MAP was greater in rats with PKD than normal rats and was increased more by caffeine. The hypertensive effect of chronic caffeine intake could not be ascribed to direct pressor effects of angiotensin II. Based on our finding that caffeine exacerbates hypertension in rats with PKD, it may be prudent for patients with ADPKD to limit coffee consumption to four or fewer cups of caffeinated coffee per day, pending studies of humans.

  2. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1

    PubMed Central

    Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

    2016-01-01

    Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

  3. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    PubMed

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. [Nucleoside-5'-triphosphate hydrolysis in the liver and kidney of rats with chronic alloxan diabetes].

    PubMed

    Rusina, I M; Makarchikov, A F; Makar, E A; Kubyshin, V L

    2006-01-01

    Activity and some properties of a soluble enzyme hydrolyzing nucleoside-5'-triphosphates were studied in the liver and kidney of normal and diabetic rats. The enzyme activity was shown to be reduced by 34% (p < 0.01) in the liver extracts of diabetic animals, while no difference was observed in the kidney. When ITP was used as substrate, the apparent Michaelis constant of the enzyme was significantly lower in the liver of controls as compared to experimental rats (32.3 +/- 1.3 microM and 54.3 +/- 1.0 microM, respectively, p < 0.01). The KM values of the enzyme in the kidney were not distinguishable in both groups. NTPase exhibits maximal activity at pH 7.0 and has a broad substrate specificity with respect to different nucleoside-5'-tri- and diphosphates. Molecular mass of the enzyme was estimated by gel filtration to be 63.7 +/- 0.9 kD.

  5. Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats.

    PubMed

    Awodele, Olufunsho; Adeneye, Adejuwon Adewale; Aiyeola, Sheriff Aboyade; Benebo, Adokiye Senibo

    2015-12-01

    There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl(-), HCO3(-)), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (p<0.05) increases in serum Na+, K+, Cl(-), urea and creatinine. CCl4 also caused significant (p<0.05) decreases in renal tissue SOD, CAT and GSH and significant (p<0.05) increases in MDA. The oral MIASE treatment (125-500 mg/kg) was found to significantly (p<0.05) attenuate the increase in serum electrolytes, urea and creatinine. Similarly, MIASE significantly (p<0.05) attenuated the decrease in SOD, CAT and GSH levels and correspondingly attenuated increases in MDA. Mangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology.

  6. Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats

    PubMed Central

    Adeneye, Adejuwon Adewale; Aiyeola, Sheriff Aboyade; Benebo, Adokiye Senibo

    2015-01-01

    There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl−, HCO3−), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (p<0.05) increases in serum Na+, K+, Cl−, urea and creatinine. CCl4 also caused significant (p<0.05) decreases in renal tissue SOD, CAT and GSH and significant (p<0.05) increases in MDA. The oral MIASE treatment (125-500 mg/kg) was found to significantly (p<0.05) attenuate the increase in serum electrolytes, urea and creatinine. Similarly, MIASE significantly (p<0.05) attenuated the decrease in SOD, CAT and GSH levels and correspondingly attenuated increases in MDA. Mangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology. PMID:27486379

  7. Effect of Eisenia foetida Extract against Cisplatin-Induced Kidney Injury in Rats.

    PubMed

    Jamshidzadeh, Akram; Heidari, Reza; Golzar, Tahereh; Derakhshanfar, Amin

    2016-01-01

    Kidney injury is a deleterious side effect accompanied by therapeutic uses of cisplatin as an antineoplastic agent. However, no therapeutic option is available against this complication. This study was designed to evaluate the protective role of a glycoprotein extract obtained from Eisenia foetida against cisplatin-induced nephrotoxicity. Rats were treated with cisplatin (7.5 mg/kg, intraperitoneally, i.p.) and Eisenia foetida extract (300 and 500 mg/kg, i.p. and/or oral). Serum creatinine (Cr) and blood urea nitrogen (BUN) were significantly elevated in cisplatin-treated rats. A significant amount of lipid peroxidation was detected in drug-treated animals. Furthermore, kidney histopathological findings revealed acute tubular necrosis and hyaline cast formation caused by cisplatin. Eisenia foetida extract administration (300 and 500 mg/kg, i.p.) significantly reduced serum BUN and creatinine and lipid peroxidation in kidney tissue. Moreover, cisplatin-induced histopathological lesions were alleviated by Eisenia foetida extract. This investigation concluded that Eisenia foetida extract ameliorated cisplatin-induced nephrotoxicity. This protection might be mediated by preventing cisplatin-induced oxidative stress.

  8. Small RNAs induce the activation of the pro-inflammatory TLR7 signaling pathway in aged rat kidney.

    PubMed

    Lee, Eun Kyeong; Chung, Ki Wung; Kim, Ye Ra; Ha, Sugyeong; Kim, Sung Dae; Kim, Dae Hyun; Jung, Kyung Jin; Lee, Bonggi; Im, Eunok; Yu, Byung Pal; Chung, Hae Young

    2017-10-01

    We have recently reported that TLR-related genes, including TLR7, are upregulated during aging. However, the role of TLR7 and its endogenous ligand in inflammation related to aging is not well defined. Here, we established that small RNAs trigger age-related renal inflammation via TLR7 signaling pathway. We first investigated the expression changes of nine different TLRs in kidney of 6-month-old young rats and 20-month-old aged rats. The results revealed that the expression of TLR7 was the highest among nine TLRs in kidney of old rats compared to the young aged rats. Next, to assess the role of cellular RNA as a TLR7 ligand, we treated a renal tubular epithelial cell line with total RNA isolated from the kidney of young and old rats. The results showed that RNA isolated from old rats showed higher expression of TLR7, IL1β, and TNFα compared to that from young rats. Furthermore, RNA isolated from old rats induced IKKα/β/JNK/NF-κB activation. To identify RNA that activates TLR7, we isolated small and large RNAs from old rat kidney and found that small RNAs increased TLR7 expression in cells. Finally, to investigate the local inflammatory response by small RNA, C57B/L6 mice were intraperitoneally injected with small RNAs isolated from young and old rats; thereby, RNA isolated from old rats induced higher inflammatory responses. Our study demonstrates that renal small RNAs from aged rats induce pro-inflammatory processes via the activation of the TLR7/IKKα/β/JNK/NF-κB signaling pathway, and highlights its causative role as a possible therapeutic target in age-related chronic renal inflammation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  9. Adverse prenatal environment and kidney development: implications for programing of adult disease.

    PubMed

    Dorey, Emily S; Pantaleon, Marie; Weir, Kristy A; Moritz, Karen M

    2014-06-01

    The 'developmental origins of health and disease' hypothesis suggests that many adult-onset diseases can be attributed to altered growth and development during early life. Perturbations during gestation can be detrimental and lead to an increased risk of developing renal, cardiovascular, metabolic, and neurocognitive dysfunction in adulthood. The kidney has emerged as being especially vulnerable to insult at almost any stage of development resulting in a reduction in nephron endowment. In both humans and animal models, a reduction in nephron endowment is strongly associated with an increased risk of hypertension. The focus of this review is twofold: i) to determine the importance of specific periods during development on long-term programing and ii) to examine the effects of maternal perturbations on the developing kidney and how this may program adult-onset disease. Recent evidence has suggested that insults occurring around the time of conception also have the capacity to influence long-term health. Although epigenetic mechanisms are implicated in mediating these outcomes, it is unclear as to how these may impact on kidney development. This presents exciting new challenges and areas for research. © 2014 Society for Reproduction and Fertility.

  10. Identification of adult nephron progenitors capable of kidney regeneration in zebrafish.

    PubMed

    Diep, Cuong Q; Ma, Dongdong; Deo, Rahul C; Holm, Teresa M; Naylor, Richard W; Arora, Natasha; Wingert, Rebecca A; Bollig, Frank; Djordjevic, Gordana; Lichman, Benjamin; Zhu, Hao; Ikenaga, Takanori; Ono, Fumihito; Englert, Christoph; Cowan, Chad A; Hukriede, Neil A; Handin, Robert I; Davidson, Alan J

    2011-02-03

    Loss of kidney function underlies many renal diseases. Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones. By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury, providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10-30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.

  11. Identification of adult nephron progenitors capable of kidney regeneration in zebrafish

    PubMed Central

    Diep, Cuong Q.; Ma, Dongdong; Deo, Rahul C.; Holm, Teresa M.; Naylor, Richard W.; Arora, Natasha; Wingert, Rebecca A.; Bollig, Frank; Djordjevic, Gordana; Lichman, Benjamin; Zhu, Hao; Ikenaga, Takanori; Ono, Fumihito; Englert, Christoph; Cowan, Chad A.; Hukriede, Neil A.; Handin, Robert I.; Davidson, Alan J.

    2011-01-01

    Loss of kidney function underlies many renal diseases1. Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones2,3. By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury4,5, providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10–30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies. PMID:21270795

  12. Thiazide diuretic drug receptors in rat kidney: Identification with ( sup 3 H)metolazone

    SciTech Connect

    Beaumont, K.; Vaughn, D.A.; Fanestil, D.D. )

    1988-04-01

    Thiazides and related diuretics inhibit NaCl reabsorption in the distal tubule through an unknown mechanism. The authors report here that ({sup 3}H)metolazone, a diuretic with a thiazide-like mechanism of action, labels a site in rat kidney membranes that has characteristics of the thiazide-sensitive ion transporter. ({sup 3}H)Metolazone bound with high affinity to a site with a density of 0.717 pmol/mg of protein in kidney membranes. The binding site was localized to the renal cortex, with little or not binding in other kidney regions and 11 other tissues. The affinities of thiazide-type diuretics for this binding site were significantly correlated with their clinical potency. Halide anions specifically inhibited high-affinity binding of ({sup 3}H)metolazone to this site. ({sup 3})Metolazone also bound with lower affinity to sites present in kidney as well as in liver, testis, lung, brain, heart, and other tissues. Calcium antagonists and certain smooth muscle relaxants had K{sub i} values of 0.6-10 {mu}M for these low-affinity sites, which were not inhibited by most of the thiazide diuretics tested. Properties of the high-affinity ({sup 3}H)metolazone binding site are consistent with its identity as the receptor for thiazide-type diuretics.

  13. Evolution of pyruvate carboxylase and other biotin containing enzymes in developing rat liver and kidney.

    PubMed

    Salto, R; Girón, M D; del Mar Sola, M; Vargas, A M

    1999-10-01

    The evolution of pyruvate carboxylase has been studied in rat liver and kidney during perinatal development. The pyruvate carboxylase activity, amount of enzyme and mRNA levels have been assayed from 2 days before delivery to weaning. In liver, there is a peak of activity and amount of enzyme 24 h before delivery and 2 peaks, at 12 h and 6 days, after parturition. The transcription of the enzyme gene followed a similar pattern, with mRNA peaks preceding those of activity and amount of enzyme. However, in kidney, pyruvate carboxylase activity, amount and mRNA remain low until weaning. These results confirm the limited role of renal gluconeogenesis during the perinatal development. Since all carboxylases contain biotin as prosthetic group, the biotinylation of pyruvate carboxylase during the perinatal period was investigated by western-blot using streptavidin-biotin peroxidase. In the mitochondrial samples from liver and kidney, all the pyruvate carboxylase detected was fully biotinylated, indicating an early development of the holocarboxylase synthetase activity in the perinatal period. This Western-blot technique also allowed us the detection of other biotin-enzymes based on their molecular weight. In liver, during the perinatal development propionyl-coA and 3-methyl-crotonyl-coA carboxylases followed a pattern of induction similar to pyruvate carboxylase. In kidney, the expression of mitochondrial carboxylases was lower compared to liver and propionyl-coA carboxylase was not detected during the studied period.

  14. The effect of angiotensin, noradrenaline and vasopressin on blood flow distribution in the rat kidney

    PubMed Central

    Finberg, J. P. M.; Peart, W. S.

    1972-01-01

    1. The effect of val5-angiotensin II amide, noradrenaline and vasopressin, on kidney volume and intrarenal distribution of carbon particles and thioflavine S was examined in the rat. 2. Angiotensin produced a dose-dependent shrinkage of the kidney coinciding with the rise in systemic blood pressure. Noradrenaline and vasopressin, however, produced reduction in kidney volume only in much higher doses than were necessary to produce a pressor effect. 3. An intravenous infusion of angiotensin sufficient to produce a diuretic response resulted in a striking increase in glomerular content of injected carbon particles, and a marked reduction in filling of the capillary plexuses of the subcortex and outer medulla. The reduction in outer medullary filling was also observed using the thioflavine S technique. 4. Noradrenaline infused in amounts sufficient to produce diuresis, aortic constriction above the kidney and vasopressin injection produced no measurable change in carbon particle distribution. 5. The reduction in capillary blood flow produced by angiotensin may result in impaired tubular reabsorptive capacity by reducing peritubular removal of reabsorbate, or by reducing oxygen availability. Thus the vasoconstrictor effects of angiotensin may explain its diuretic action. ImagesPlate 1Plate 2 PMID:4333828

  15. Protective effects of exogenous β-hydroxybutyrate on paraquat toxicity in rat kidney.

    PubMed

    Wei, Teng; Tian, Wulin; Liu, Fangning; Xie, Guanghong

    2014-05-16

    In this study, we demonstrated the protective effects of β-hydroxybutyrate (β-HB) against paraquat (PQ)-induced kidney injury and elucidated the underlying molecular mechanisms. By histological examination and renal dysfunction specific markers (serum BUN and creatinine) assay, β-HB could protect the PQ-induced kidney injury in rat. PQ-induced kidney injury is associated with oxidative stress, which was measured by increased lipid peroxidation (MDA) and decreased intracellular anti-oxidative abilities (SOD, CAT and GSH). β-HB pretreatment significantly attenuated that. Caspase-mediated apoptosis pathway contributed importantly to PQ toxicity, as revealed by the activation of caspase-9/-3, cleavage of PARP, and regulation of Bcl-2 and Bax, which were also effectively blocked by β-HB. Moreover, treatment of PQ strongly decreased the nuclear Nrf2 levels. However, pre-treatment with β-HB effectively suppressed this action of PQ. This may imply the important role of β-HB on Nrf2 pathway. Taken together, this study provides a novel finding that β-HB has a renoprotective ability against paraquat-induced kidney injury. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Alterations in the metabolomics of sulfur-containing substances in rat kidney by betaine.

    PubMed

    Kim, Young Chul; Kwon, Do Young; Kim, Ji Hyun

    2014-04-01

    Earlier studies have shown that betaine administration may modulate the metabolism of sulfur amino acids in the liver. In this study, we determined the changes in the metabolomics of sulfur-containing substances induced by betaine in the kidney, the other major organ actively involved in the transsulfuration reactions. Male rats received betaine (1%) in drinking water for 2 weeks before killing. Betaine intake did not affect betaine-homocysteine methyltransferase activity or its protein expression in the renal tissue. Expression of methionine synthase was also unchanged. However, methionine levels were increased significantly both in plasma and kidney. Renal methionine adenosyltransferase activity and S-adenosylmethionine concentrations were increased, but there were no changes in S-adenosylhomocysteine, homocysteine, cysteine levels or cystathionine β-synthase expression. γ-Glutamylcysteine synthetase expression or glutathione levels were not altered, but cysteine dioxygenase and taurine levels were decreased significantly. In contrast, betaine administration induced cysteine sulfinate decarboxylase and its metabolic product, hypotaurine. These results indicate that the metabolomics of sulfur-containing substances in the kidney is altered extensively by betaine, although the renal capacity for methionine synthesis is unresponsive to this substance unlike that of the liver. It is suggested that the increased methionine availability due to an enhancement of its uptake from plasma may account for the alterations in the metabolomics of sulfur-containing substances in the kidney. Further studies need to be conducted to clarify the physiological/pharmacological significance of these findings.

  17. Potassium depletion downregulates chloride-absorbing transporters in rat kidney.

    PubMed Central

    Amlal, H; Wang, Z; Soleimani, M

    1998-01-01

    Potassium depletion (KD) causes renal chloride wasting, suggesting defect(s) in Cl- reabsorption in renal tubules. To determine whether alterations in expression of the major Cl- transporter genes might contribute to the chloride wasting, we analyzed their expression in renal cortex and medulla of animals placed on KD diet. Feeding KD diet to rats resulted in significant hypokalemia at 14 d but not at 6 d. Northern hybridization revealed that mRNA levels for the apical Na-K-2Cl cotransporter in the medulla decreased by 56 and 51% at 6 and 14 d of KD diet, respectively. Functional studies in tubular suspensions from medullary thick ascending limb demonstrated that the Na-K-2Cl cotransporter activity decreased by approximately 45 and approximately 37% at 6 and 14 d of KD diet, respectively. mRNA levels for the thiazide-sensitive Na-Cl cotransporter decreased by 57 and 64% at 6 and 14 d of KD diet. Decreased expression of the apical Na-Cl and the Na-K-2Cl cotransporters became evident at 48 and 72 h of KD, respectively. Urinary chloride excretion increased at 48 h and further increased at 72 h of KD, correlating with suppression of the Na-Cl and the Na-K-2Cl transporters. Our results indicate that increased urinary chloride loss in KD results from suppression of the chloride-absorbing transporters. Downregulation of chloride transporters in KD is an early event and can lead to hypochloremia and subsequently hypovolemia and decreased glomerular filtration rate. PMID:9486975

  18. Clinical Manifestations of Kidney Disease Among US Adults With Diabetes, 1988-2014.

    PubMed

    Afkarian, Maryam; Zelnick, Leila R; Hall, Yoshio N; Heagerty, Patrick J; Tuttle, Katherine; Weiss, Noel S; de Boer, Ian H

    2016-08-09

    Diabetic kidney disease is the leading cause of chronic and end-stage kidney disease in the United States and worldwide. Changes in demographics and treatments may affect the prevalence and clinical manifestations of diabetic kidney disease. To characterize the clinical manifestations of kidney disease among US adults with diabetes over time. Serial cross-sectional studies of adults aged 20 years or older with diabetes mellitus participating in National Health and Nutrition Examination Surveys from 1988 through 2014. Diabetes was defined as hemoglobin A1c greater than 6.5% or use of glucose-lowering medications. Albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), macroalbuminuria (urine albumin-to-creatinine ratio ≥300 mg/g), reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2), and severely reduced eGFR (<30 mL/min/1.73 m2), incorporating data on biological variability to estimate the prevalence of persistent abnormalities. There were 6251 adults with diabetes included (1431 from 1988-1994, 1443 from 1999-2004, 1280 from 2005-2008, and 2097 from 2009-2014). The prevalence of any diabetic kidney disease, defined as persistent albuminuria, persistent reduced eGFR, or both, did not significantly change over time from 28.4% (95% CI, 23.8%-32.9%) in 1988-1994 to 26.2% (95% CI, 22.6%-29.9%) in 2009-2014 (prevalence ratio, 0.95 [95% CI, 0.86-1.06] adjusting for age, sex, and race/ethnicity; P = .39 for trend). However, the prevalence of albuminuria decreased progressively over time from 20.8% (95% CI, 16.3%-25.3%) in 1988-1994 to 15.9% (95% CI, 12.7%-19.0%) in 2009-2014 (adjusted prevalence ratio, 0.76 [95% CI, 0.65-0.89]; P < .001 for trend). In contrast, the prevalence of reduced eGFR increased from 9.2% (95% CI, 6.2%-12.2%) in 1988-1994 to 14.1% (95% CI, 11.3%-17.0%) in 2009-2014 (adjusted prevalence ratio, 1.61 [95% CI, 1.33-1.95] comparing 2009-2014 with 1988-1994; P < .001 for trend), with a similar pattern for severely

  19. Synthesis of bile acid monosulphates by the isolated perfused rat kidney.

    PubMed Central

    Summerfield, J A; Gollan, J L; Billing, B H

    1976-01-01

    Perfusion of an isolated rat kidney with labelled bile acids, in a protein-free medium, resulted in the urinary excretion of the labelled bile acid, 3% being converted into polar metabolities in 1h. These metabolities were neither glycine nor taurine conjugates, nor bile acid glucuronides, and on solovolysis yielded the free bile acid. On t.l.c. the metabolite of [24-14C]lithocholic acid had the mobility of lithocholate 3-sulphate. The principal metabolite of [24-14C]chenodeoxycholic acid had the mobility of chenodeoxycholate 7-sulphate; trace amounts appeared as chenodeoxycholate 3-sulphate. [35S]sulphate was incorporated in chenodeoxycholic acid by the kidney, resulting in a similar pattern of sulphation. No disulphate salt of chenodeoxycholic acid was detected. These findings lend support to the hypothesis that renal synthesis may account for some of the bile acid sulphates present in urine in the cholestatic syndrome in man. PMID:942413

  20. The isolated perfused rat kidney model: a useful tool for drug discovery and development.

    PubMed

    Taft, David R

    2004-01-01

    Over the past three decades, the Isolated Perfused Rat Kidney (IPK) has been used to study numerous aspects of renal drug disposition. Among the available ex-vivo methods to study renal transport, the IPK allows for elucidation of the overall contributions of renal transport mechanisms on drug excretion. Therefore, IPK studies can provide a bridge between in vitro findings and in vivo disposition. This review paper begins with a detailed overview of IPK methodology (system components, surgical procedure, study design). Various applications of the IPK are then presented. These applications include characterizing renal excretion mechanisms, screening for clinically significant drug interactions, studying renal drug metabolism, and correlating renal drug disposition with drug-induced changes in kidney function. Lastly, the role of IPK studies in drug development is discussed. Demonstrated correlations between IPK data and clinical outcomes make the IPK model a potentially useful tool for drug discovery and evaluation.

  1. Effect of dimethylaminoethanol, an inhibitor of betaine production, on the disposition of choline in the rat kidney

    SciTech Connect

    Lohr, J.; Acara, M. )

    1990-01-01

    The choline metabolite betaine has been shown to be an important organic osmoregulatory solute in the kidney. The isolated perfused rat kidney and kidney slice incubations were used to investigate the effect of 2-dimethylaminoethanol (DMAE), a choline oxidase inhibitor, on the renal excretion and metabolism of choline. In the isolated perfused kidney, ({sup 14}C)choline, at an initial perfusate concentration of 300 microM, was effectively removed from the perfusate over 25 min, with nearly all the {sup 14}C in the perfusate accounted for by betaine during the remainder of the 90-min perfusion. DMAE at concentrations of 3.0 or 5.0 mM significantly decreased the rate of removal of ({sup 14}C)choline from the perfusate and the rate of addition of ({sup 14}C)betaine to the perfusate, yet (14C)betaine remained the only metabolite of choline in perfusate and urine. In kidney tissue slice experiments, conversion of ({sup 14}C)choline to ({sup 14}C)betaine was found in cortical, outer medullary and inner medullary regions of rat kidney. DMAE at 5.0 mM significantly inhibited ({sup 14}C)betaine production in each of the three regions studied. These data show that DMAE is an effective inhibitor of betaine production by the kidney and, as such, may be an important agent for the study of osmoregulation by the kidney.

  2. Age-related change of endocytic receptors megalin and cubilin in the kidney in rats.

    PubMed

    Odera, Keiko; Goto, Sataro; Takahashi, Ryoya

    2007-10-01

    Megalin and cubilin are the major endocytic receptors responsible for resorption of glomerular filtrate proteins, particularly albumin, in the renal proximal tubule. In order to better understand the mechanism of the development of albuminuria with age in rats, we investigated age-related change of the amount and cellular localization of both receptors in the kidney. Immunoblot analysis of the kidney extracts showed that the amount of megalin significantly decreased with age. Although there was no age-related change in the amount of intact cubilin, the amount of cubilin fragments increased with age. Immunohistochemical study revealed that megalin and cubilin were predominantly localized in brush border membrane of proximal tubular cells in young rats, but the receptors tended to diffuse into the cytoplasm in the old rats. Interestingly, low but significant amounts of megalin and cubilin were present in the glomerular cells in addition to the proximal tubular cells. The quantity of receptors progressively increased in the glomerulus with age. This age-related increase might be to compensate for the age-related defect of the uptake of albumin by the proximal tubules. Thus, although it is unclear whether megalin and cubilin in the glomerulus contribute to the uptake of albumin in primary urine, the age-related increase in the amount of albumin in urine might at least partly be due to quantitative and qualitative alterations of both receptors in the proximal tubule.

  3. The protective effect of Malva sylvestris on rat kidney damaged by vanadium

    PubMed Central

    2011-01-01

    Background The protective effect of the common mallow (Malva sylvestris) decoction on renal damages in rats induced by ammonium metavanadate poisoning was evaluated. On the one hand, vanadium toxicity is associated to the production of reactive oxygen species, causing a lipid peroxidation and an alteration in the enzymatic antioxidant defence. On the other hand, many medicinal plants are known to possess antioxidant and radical scavenging properties, thanks to the presence of flavonoids. These properties were confirmed in Malva sylvestris by two separate methods; namely, the Diphenyl-2-picrylhydrazyl assay and the Nitroblue Tetrazolium reduction assay. Results In 80 rats exposed to ammonium metavanadate (0.24 mmol/kg body weight in drinking water) for 90 days, lipid peroxidation levels and superoxide dismutase, catalase and glutathione peroxidase activities were measured in kidney. A significant increase in the formation of free radicals and antioxidant enzyme activities was noticed. In addition, a histological examination of kidney revealed a structural deterioration of the renal cortical capsules and a shrinking of the Bowman space. In animals intoxicated by metavanadate but also given a Malva sylvestris decoction (0.2 g dry mallow/kg body weight), no such pathologic features were observed: lipid peroxidation levels, antioxidant enzyme activities and histological features appeared normal as compared to control rats. Conclusion Malva sylvestris is proved to have a high antioxidative potential thanks to its richness in phenolic compounds. PMID:21513564

  4. The protective effect of Malva sylvestris on rat kidney damaged by vanadium.

    PubMed

    Marouane, Wafa; Soussi, Ahlem; Murat, Jean-Claude; Bezzine, Sofiane; El Feki, Abdelfattah

    2011-04-23

    The protective effect of the common mallow (Malva sylvestris) decoction on renal damages in rats induced by ammonium metavanadate poisoning was evaluated. On the one hand, vanadium toxicity is associated to the production of reactive oxygen species, causing a lipid peroxidation and an alteration in the enzymatic antioxidant defence. On the other hand, many medicinal plants are known to possess antioxidant and radical scavenging properties, thanks to the presence of flavonoids. These properties were confirmed in Malva sylvestris by two separate methods; namely, the Diphenyl-2-picrylhydrazyl assay and the Nitroblue Tetrazolium reduction assay. In 80 rats exposed to ammonium metavanadate (0.24 mmol/kg body weight in drinking water) for 90 days, lipid peroxidation levels and superoxide dismutase, catalase and glutathione peroxidase activities were measured in kidney. A significant increase in the formation of free radicals and antioxidant enzyme activities was noticed. In addition, a histological examination of kidney revealed a structural deterioration of the renal cortical capsules and a shrinking of the Bowman space. In animals intoxicated by metavanadate but also given a Malva sylvestris decoction (0.2 g dry mallow/kg body weight), no such pathologic features were observed: lipid peroxidation levels, antioxidant enzyme activities and histological features appeared normal as compared to control rats. Malva sylvestris is proved to have a high antioxidative potential thanks to its richness in phenolic compounds.

  5. Localization and induction by dehydration of ClC-K chloride channels in the rat kidney.

    PubMed

    Vandewalle, A; Cluzeaud, F; Bens, M; Kieferle, S; Steinmeyer, K; Jentsch, T J

    1997-05-01

    We investigate the intrarenal expression of two recently cloned chloride channels, rClC-K1 and rClC-K2, by reverse transcriptase-polymerase chain reaction on single microdissected tubules from the rat kidney and by immunohistochemistry using a polyclonal antibody that recognizes both highly homologous channels. Both rClC-K1 and rClC-K2 mRNAs were detected in outer medullary late proximal tubules (S3), papillary ascending thin limbs (ATL), and outer medullary (MTAL) and cortical (CTAL) thick ascending limbs, distal tubules (DCT), and cortical, outer medullary, and inner medullary collecting ducts. Indirect immunofluorescence studies demonstrated that the rClC-K proteins were restricted to the basolateral membranes from ATL, DCT, and collecting ducts cells, whereas CTAL and MTAL exhibited a more diffuse basal staining. When rats were dehydrated, a condition which increased the expression of rClC-K1 in cortex and medulla, a weak cytoplasmic staining was found in late proximal tubule cells. Thus these results demonstrate that rat kidney ClC-K channels are predominantly located in the basolateral membranes from cells of the late segments of the renal tubule where most of chloride reabsorption takes place.

  6. SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model

    PubMed Central

    Xu, Siqi; Wei, Siwei; Dai, Xingui

    2016-01-01

    Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI. PMID:28003866

  7. Rosuvastatin Treatment Prevents Progressive Kidney Inflammation and Fibrosis in Stroke-Prone Rats

    PubMed Central

    Gianella, Anita; Nobili, Elena; Abbate, Mauro; Zoja, Carla; Gelosa, Paolo; Mussoni, Luciana; Bellosta, Stefano; Canavesi, Monica; Rottoli, Daniela; Guerrini, Uliano; Brioschi, Maura; Banfi, Cristina; Tremoli, Elena; Remuzzi, Giuseppe; Sironi, Luigi

    2007-01-01

    Salt-loaded, spontaneously hypertensive stroke-prone rats show progressive increases in blood pressure and proteinuria and accumulate acute-phase proteins in body fluids, modeling events during renal damage. The aim of this study was to assess the pathological events occurring in the kidney of spontaneously hypertensive stroke-prone rats over time and evaluate the effects of statin treatment, which is known to improve renal and cardiovascular outcomes. Kidneys of male spontaneously hypertensive stroke-prone rats euthanized at different stages of proteinuria showed progressive inflammatory cell infiltration, the accumulation of α-smooth muscle actin-positive cells, degenerative changes in podocytes, and severe fibrosis. These were accompanied by an imbalance in the plasminogen/plasmin and metalloprotease systems characterized by the increased renal expression of plasminogen activator inhibitor-1, tissue plasminogen activator, and urokinase plasminogen activator; the net result was an increase in plasmin and matrix metalloproteinase (MMP)-2 and a reduction in MMP-9 activity. Chronic treatment with the hydrophilic rosuvastatin had renoprotective effects in terms of morphology and inflammation and prevented the changes in plasmin, MMP-2, and MMP-9 activity. These effects were independent of the changes in blood pressure and plasma lipid levels. Treatment with the lipophilic simvastatin was not renoprotective. These data suggest that rosuvastatin may have potential utility as a therapeutic option in renal diseases that are characterized by inflammation and fibrosis. PMID:17392157

  8. Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

    NASA Astrophysics Data System (ADS)

    Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael; Motta, Mariana H.; Ribeiro, Roseane F.; dos S. Hausen, Bruna; Moresco, Rafael N.; Garcia, Solange C.; da Silva, Cristiane B.; Burger, Marilise E.

    2015-04-01

    Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups ( n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

  9. Predicting Major Adverse Kidney Events among Critically Ill Adults Using the Electronic Health Record.

    PubMed

    McKown, Andrew C; Wang, Li; Wanderer, Jonathan P; Ehrenfeld, Jesse; Rice, Todd W; Bernard, Gordon R; Semler, Matthew W

    2017-08-31

    Prediction of major adverse kidney events in critically ill patients may help target therapy, allow risk adjustment, and facilitate the conduct of clinical trials. In a cohort comprised of all critically ill adults admitted to five intensive care units at a single tertiary care center over one year, we developed a logistic regression model for the outcome of Major Adverse Kidney Events within 30 days (MAKE30), the composite of persistent renal dysfunction, new renal replacement therapy (RRT), and in-hospital mortality. Proposed risk factors for the MAKE30 outcome were selected a priori and included age, race, gender, University Health System Consortium (UHC) expected mortality, baseline creatinine, volume of isotonic crystalloid fluid received in the prior 24 h, admission service, intensive care unit (ICU), source of admission, mechanical ventilation or receipt of vasopressors within 24 h of ICU admission, renal replacement therapy prior to ICU admission, acute kidney injury, chronic kidney disease as defined by baseline creatinine value, and renal failure as defined by the Elixhauser index. Among 10,983 patients in the study population, 1489 patients (13.6%) met the MAKE30 endpoint. The strongest independent predictors of MAKE30 were UHC expected mortality (OR 2.32 [95%CI 2.06-2.61]) and presence of acute kidney injury at ICU admission (OR 4.98 [95%CI 4.12-6.03]). The model had strong predictive properties including excellent discrimination with a bootstrap-corrected area-under-the-curve (AUC) of 0.903, and high precision of calibration with a mean absolute error prediction of 1.7%. The MAKE30 composite outcome can be reliably predicted from factors present within 24 h of ICU admission using data derived from the electronic health record.

  10. Cellular engineering of ventricular adult rat cardiomyocytes.

    PubMed

    Weikert, Christian; Eppenberger-Eberhardt, Monika; Eppenberger, Hans M

    2003-10-01

    Preparation of viable cultured adult cardiomyocytes (vARCs) is a prerequisite for cell-based transplantation and tissue engineering. Ectopic gene expression is important in this context. Here, we present an in vitro cell replating strategy using Accutase for cultured vARCs, allowing ectopic gene expression. Cultured vARCs from 6- to 8-week-old rats were used. Transfections with EGFP (enhanced green fluorescent protein) constructs, Mlc-3f-EGFP or alpha-actinin-EGFP were performed using adenovirus-enhanced transferrin-mediated infection (AVET). Accutase (PAA Laboratories, Linz, Austria) was used for the detachment of cultured cells. Immunohistochemical analysis, together with confocal laser microscopy was used for structural analysis of the cells. Cultured vARCs could be detached with a high yield (40 to 60%) from primary cultures using Accutase. The cultivation period plays an important role in the yield of viable cells. Resultant replated vARCs (rep-vARCs) rapidly (1-2 h) acquired a rounded up shape without degradation of their contractile apparatus, which is in contrast to the rod-shaped freshly isolated vARCs (fi-vARCs). The detached cells survived passage through a narrow syringe needle. After seeding, detached cells rapidly attached to various substrates, increased their content of the contractile apparatus, and formed cell-cell contacts within 3 days after reseeding. The detached cells survived passage through a narrow syringe needle. The high recovery of cells after replating enabled the use of the AVET system for gene delivery. AVET is free of infectious particles and does not lead to expression of viral proteins. Transfection of vARCs prior to detachment had a small effect on cell recovery and ectopically synthesized proteins were properly localized after replating. Detachment of cultured vARCs using Accutase is well compatible with ectopic gene expression and yields a viable transgenic population of vARCs that eventually may be suitable as transgenic

  11. Effects of benidipine and candesartan on kidney and vascular function in hypertensive Dahl rats.

    PubMed

    Yao, Kozo; Sato, Hitoshi; Sonoda, Rie; Ina, Yasuhiro; Suzuki, Kazuo; Ohno, Tetsuji

    2003-07-01

    We examined the effect of the dihydropyridine calcium channel blocker (CCB) benidipine, the angiotensin II type 1 receptor blocker (ARB) candesartan, and the combination of these drugs on blood pressure and kidney and vascular function in rats with salt-induced hypertension. Dahl salt-sensitive (DS) rats were fed with a high-salt (8% NaCl) diet from 7 weeks of age. Benidipine (1, 3 mg/kg), candesartan (1, 3 mg/kg), benidipine (3 mg/kg) combined with candesartan (3 mg/kg), or vehicle was administered orally after the start of the feeding. Relaxant responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) were measured to examine the vascular function. DS rats fed the high-salt diet showed an increase in systolic blood pressure (SBP), which was accompanied by glomerular sclerosis and an increase in urinary albumin excretion. Relaxant responses to acetylcholine and sodium nitroprusside were impaired in superior mesenteric arterial rings from the hypertensive DS rats. SBP was significantly lower in all of the drug-treated groups than in the vehicle-treated group. The antihypertensive effect of benidipine at 3 mg/kg was more potent than that of candesartan at 3 mg/kg. The albuminuria was significantly decreased in the benidipine and benidipine plus candesartan groups, but not in the candesartan group. The level of SBP in the benidipine plus candesartan group was lower than that by either drug alone. In addition, benidipine alone and benidipine plus candesartan inhibited the glomerular sclerosis and the impairment of relaxant responses in the arteries. These results demonstrate that benidipine is more effective than candesartan in lowering blood pressure and preventing the impairment of kidney and vascular function in salt-sensitive hypertensive rats. In addition, the results suggest that combination therapy with benidipine and an ARB decreases blood pressure more effectively than either drug alone

  12. NFAT5 Is Activated by Hypoxia: Role in Ischemia and Reperfusion in the Rat Kidney

    PubMed Central

    Villanueva, Sandra; Suazo, Cristian; Santapau, Daniela; Pérez, Francisco; Quiroz, Mariana; Carreño, Juan E.; Illanes, Sebastián; Lavandero, Sergio; Michea, Luis; Irarrazabal, Carlos E.

    2012-01-01

    The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting in cell protection. Additionally, the renal medulla is hypoxic (10–18 mmHg); however there is no information about the effect of hypoxia on NFAT5. Using in vivo and in vitro models, we evaluated the effect of reducing the partial pressure of oxygen (PO2) on NFAT5 activity. We found that 1) Anoxia increased NFAT5 expression and nuclear translocation in primary cultures of IMCD cells from rat kidney. 2) Anoxia increased transcriptional activity and nuclear translocation of NFAT5 in HEK293 cells. 3) The dose-response curve demonstrated that HIF-1α peaked at 2.5% and NFAT5 at 1% of O2. 4) At 2.5% of O2, the time-course curve of hypoxia demonstrated earlier induction of HIF-1α gene expression than NFAT5. 5) siRNA knockdown of NFAT5 increased the hypoxia-induced cell death. 6) siRNA knockdown of HIF-1α did not affect the NFAT5 induction by hypoxia. Additionally, HIF-1α was still induced by hypoxia even when NFAT5 was knocked down. 7) NFAT5 and HIF-1α expression were increased in kidney (cortex and medulla) from rats subjected to an experimental model of ischemia and reperfusion (I/R). 7) Experimental I/R increased the NFAT5-target gene aldose reductase (AR). 8) NFAT5 activators (ATM and PI3K) were induced in vitro (HEK293 cells) and in vivo (I/R kidneys) with the same timing of NFAT5. 8) Wortmannin, which inhibits ATM and PI3K, reduces hypoxia-induced NFAT5 transcriptional activation in HEK293 cells. These results demonstrate for the first time that NFAT5 is induced by hypoxia and could be a protective factor against ischemic damage. PMID:22768306

  13. The chloride-bicarbonate exchanger pendrin is increased in the kidney of the pregnant rat.

    PubMed

    West, Crystal A; Verlander, Jill W; Wall, Susan M; Baylis, Chris

    2015-10-01

    What is the central question of this study? Pregnancy requires a robust plasma volume expansion driven by renal sodium retention. In the late-pregnant kidney, the aldosterone-responsive epithelial Na(+) channel is increased, whereas the sodium-chloride cotransporter is decreased. Pendrin has been shown to support sodium reabsorption in the distal nephron and compensate for loss of the sodium-chloride cotransporter. We investigated the expression and abundance of pendrin in the pregnant kidney. What is the main finding and its importance? Pendrin protein, apical localization and thiazide sensitivity are increased in pregnancy. This implicates a possible role for pendrin in supporting the renal sodium chloride reabsorption and plasma volume expansion of pregnancy. Pregnancy is characterized by cumulative plasma volume expansion as a result of renal sodium retention, driven by activation of aldosterone. We previously reported that the abundance and activity of the aldosterone-responsive epithelial Na(+) channel is increased, whereas the sodium-chloride cotransporter (NCC) is decreased in the kidney of the late-pregnant rat. The chloride-bicarbonate exchanger pendrin is also aldosterone responsive and has been shown to support activity of the aldosterone-responsive epithelial Na(+) channel and compensate for the loss of NCC. Additionally, pendrin coupled to the sodium-dependent chloride-bicarbonate exchanger (NDCBE) mediates thiazide-sensitive sodium reabsorption in the cortical collecting duct. In this study, we investigated pendrin and NDCBE transcript expression, pendrin protein abundance, pendrin cellular localization and thiazide sensitivity in virgin, mid-pregnant and late-pregnant rats to test the hypothesis that increased pendrin activity might occur in pregnancy. By RT-PCR, NDCBE and pendrin mRNA expression was unchanged from virgins, whereas pendrin protein abundance determined by Western blotting was increased in both mid- and late-pregnant rats. The apical

  14. Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

    SciTech Connect

    Liu, Chan-Min; Ma, Jie-Qiong; Sun, Yun-Zhi

    2012-02-01

    Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against lead (Pb) induced injury in kidney have not been clarified. The aim of the present study was to investigate the effects of puerarin on renal oxidative stress and apoptosis in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water (500 mg Pb/l) with or without puerarin co-administration (100, 200, 300 and 400 mg PU/kg intragastrically once daily) for 75 days. Our data showed that puerarin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of kidney damage (serum urea, uric acid and creatinine) and histopathological analysis. Moreover, Pb-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of intracellular reduced glutathione (GSH) level in kidney, were suppressed by treatment with puerarin. Furthermore, TUNEL assay showed that Pb-induced apoptosis in rat kidney was significantly inhibited by puerarin. In exploring the underlying mechanisms of puerarin action, we found that activities of caspase-3 were markedly inhibited by the treatment of puerarin in the kidney of Pb-treated rats. Puerarin increased phosphorylated Akt, phosphorylated eNOS and NO levels in kidney, which in turn inactivated pro-apoptotic signaling events including inhibition of mitochondria cytochrome c release and restoration of the balance between pro- and anti-apoptotic Bcl-2 proteins in kidney of Pb-treated rats. In conclusion, these results suggested that the inhibition of Pb-induced apoptosis by puerarin is due at least in part to its antioxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway. Highlights: ► Puerarin prevented lead-induced nephrototoxicity. ► Puerarin reduced lead-induced increase in ROS and TBARS production

  15. Effects of salt restriction on renal growth and glomerular injury in rats with remnant kidneys.

    PubMed

    Lax, D S; Benstein, J A; Tolbert, E; Dworkin, L D

    1992-06-01

    Male Munich-Wistar rats underwent right nephrectomy and infarction of two thirds of the left kidney. Rats were randomly assigned to ingest standard chow (REM) or a moderately salt restricted chow (LS). A third group of rats were fed the low salt diet and were injected with an androgen (LSA). Eight weeks after ablation, glomerular volume and glomerular capillary radius were markedly increased in REM. This increase was prevented by the low salt diet, however, the antihypertrophic effect of the diet was overcome by androgen. Values for glomerular volume and capillary radius were similar in LSA and REM. Morphologic studies revealed that approximately 25% of glomeruli were abnormal in REM. Much less injury was observed in salt restricted rats, however, the protective effect of the low salt diet was significantly abrogated when renal growth was stimulated in salt restricted rats by androgen. Micropuncture studies revealed that glomerular pressure was elevated in all three groups and not affected by diet or androgen. Serum cholesterol was also similar in the three groups. These findings indicate that renal and glomerular hypertrophy are correlated with the development of glomerular injury after reduction in renal mass and suggest that dietary salt restriction lessens renal damage, at least in part, by inhibiting compensatory renal growth.

  16. Protective effect of green tea extract against proline-induced oxidative damage in the rat kidney.

    PubMed

    Delwing-Dal Magro, Débora; Roecker, Roberto; Junges, Gustavo M; Rodrigues, André F; Delwing-de Lima, Daniela; da Cruz, José G P; Wyse, Angela T S; Pitz, Heloisa S; Zeni, Ana L B

    2016-10-01

    We investigated, in vivo (acute and chronic), the effects of proline on thiobarbituric acid-reactive substances (TBA-RS) and on the activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in renal tissues (cortex and medulla) of rats. For acute administration, 29-day-old rats received a single subcutaneous injection of proline (18.2μmol/g body weight) or an equivalent volume of 0.9% saline solution and were sacrificed 1h later. For chronic treatment, proline was injected subcutaneously in the rats twice a day from the 6th to the 28th day of age, and the animals were killed 12h after the last injection. The results showed that acute administration of proline enhanced CAT, SOD and GSH-Px activities, as well as, TBARS in the cortex and decreased CAT activity in the medulla, while chronic treatment increased the activities of SOD in the cortex and increased CAT, SOD and GSH-Px in the medulla of rats. Furthermore, the green tea extract treatment for one week or from the 6th to the 28th day of age prevented the alterations caused by acute and chronic, respectively, proline administration. Herein, we demonstrated that proline alters antioxidant defenses and induces lipid peroxidation in the kidney of rats and the green tea extract was capable to counteract the proline-induced alterations.

  17. Effects of fluid resuscitation with 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis*.

    PubMed

    Zhou, Feihu; Peng, Zhi-Yong; Bishop, Jeffery V; Cove, Matthew E; Singbartl, Kai; Kellum, John A

    2014-04-01

    To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Controlled laboratory experiment. University laboratory. Sixty adult, male Sprague-Dawley rats. We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals. Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury. Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short-term survival when compared with 0.9% saline in this experimental animal model of sepsis.

  18. Effects of Fluid Resuscitation With 0.9% Saline Versus a Balanced Electrolyte Solution on Acute Kidney Injury in a Rat Model of Sepsis*

    PubMed Central

    Zhou, Feihu; Peng, Zhi-Yong; Bishop, Jeffery V.; Cove, Matthew E.; Singbartl, Kai; Kellum, John A.

    2014-01-01

    Objective To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Design Controlled laboratory experiment. Setting University laboratory. Subjects Sixty adult, male Sprague-Dawley rats. Interventions We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals. Measurements and Main Results Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury. Conclusion Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short

  19. Glomerulonephritis-Induced Changes in Urinary and Kidney MicroRNA Profiles in Rats.

    PubMed

    Pavkovic, Mira; Riefke, Björn; Frisk, Anna-Lena; Gröticke, Ina; Ellinger-Ziegelbauer, Heidrun

    2015-06-01

    MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and thus are involved in various physiological and pathological states. Due to their stability in biofluids miRNAs have also been proposed as biomarkers (BMs) for tissue injury. We investigated the usefulness of urinary miRNAs for detection of site-specific renal damage in an antiglomerular basement membrane glomerulonephritis (GN) model in rats by comparing GN-induced urinary miRNAs profiles to traditional and newer protein BMs, and to proximal tubular injury-induced urinary miRNA profiles observed previously after cisplatin (Cp) treatment. Male Wistar Kyoto and Sprague Dawley rats were dosed once with 1, 2.5, and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days. Although serum creatinine and BUN were not changed, several protein BMs and 74 urinary miRNAs were found to be increased 8 and 14 days after NTS administration. Of these 74 miRNAs, 5 were identified as increased after NTS but not after Cp treatment. Using in situ hybridization two of them, miR-10 b and -100, were found to be localized in distal segments of the nephron, potentially reflecting the tubular injury in those regions. Furthermore, evaluation of both miRNA and mRNA expression in the kidney revealed possible miRNA-mRNA interactions mostly associated with fibrotic and transforming growth factor β signaling. In conclusion, our investigations support the potential of urinary miRNAs as specific BMs for kidney injury, and suggest a role of miRNAs in pathological processes during GN in the kidney.

  20. Allicin ameliorates kidney function and urinary bladder sensitivity in cyclosporine A-treated rats.

    PubMed

    El-Kashef, D H; El-Kenawi, A E; Suddek, G M; Salem, H A

    2016-09-05

    Cyclosporine-A (CsA) is an immunosuppressive drug which has been used to prevent rejection after organ transplantation and to treat certain autoimmune diseases. However, its therapeutic use is limited by nephrotoxicity. In this study, the modulator effect of allicin on the oxidative nephrotoxicity of CsA in rats was investigated. Furthermore, the effect of allicin on CsA-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was estimated. Rats were divided into three groups, control, CsA (15 mg/kg, subcutaneously), and CsA/allicin (50 mg/kg, orally). At the end of the study, all rats were killed and then blood, urine samples, and kidneys were taken. CsA administration caused a severe nephrotoxicity which was evidenced by elevated kidney/body weight ratio, serum creatinine (Cr), blood urea nitrogen, lactate dehydrogenase, and urinary protein with a concomitant reduction in serum albumin and Cr clearance as compared with control. A significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione, superoxide dismutase activities, and nitric oxide (NOx) content was detected upon CsA administration. Exposure to CsA increased the sensitivity of isolated urinary bladder rings to ACh. Histological analysis revealed that CsA caused tubular necrosis and moderate diffuse tubular atrophy. Allicin protected kidney tissue against the oxidative damage and the nephrotoxic effect of CsA and significantly reduced the responses of isolated bladder rings to ACh. Our study indicates that allicin administration has the potential to protect against CsA-induced renal injury by reducing oxidative stress and inflammation and restoring NOx level.

  1. Urate excretion by the isolated perfused rat kidney and modification by drugs.

    PubMed

    MacDougall, M L; Wiegmann, T B

    1989-12-01

    Urate excretion in the isolated perfused rat kidney was studied over a wide range of perfusate urate concentrations (13.9-376.8 microM). Fractional excretion of urate (FEurate) averaged 57.9 +/- 2.0% (range, 58.5-59.6%), showed marked interanimal variability, but was not dependent on the perfusate-free urate concentration. In paired experiments, the effects of five drugs (probenecid, pyrazinoate, furosemide, salicylate, and oxonate) on FEurate were evaluated. A low concentration of pyrazinoate (0.2 mM) decreased FEurate (62.0 +/- 1.9 vs 53.8 +/- 2.4%, P less than 0.05), as did 0.8 mM pyrazinoate (59.5 +/- 2.4 vs 48.4 +/- 2.7%, P less than 0.05). Probenecid (1 mM) decreased FEurate (59.3 +/- 3.1 vs 52.0 +/- 2.5%, P less than 0.05) but 2.5 mM probenecid did not alter FEurate (48.0 +/- 6.3 vs 47.8 +/- 6.9%). Oxonate (0.1 mM) also decreased FEurate (75.8 +/- 4.2 vs 67.1 +/- 2.1%, P less than 0.05) while 0.2 mM oxonate had no effect (66.4 +/- 3.5 vs 61.5 +/- 4.6%). Neither salicylate nor furosemide affected FEurate, although both drugs caused a saliuresis and diuresis. Thus, urate transport in rat kidneys in vitro is not dependent on urate concentration, unlike man. Some drugs known to affect urate excretion in humans and rats did not have similar effects in isolated kidneys. Isolated organ studies provide additional information is understanding renal urate handling.

  2. Strain differences in urinary factors that promote calcium oxalate crystal formation in the kidneys of ethylene glycol-treated rats.

    PubMed

    Li, Yan; McMartin, Kenneth E

    2009-05-01

    Ethylene glycol (EG)-induced hyperoxaluria is the most commonly employed experimental regimen as an animal model of calcium oxalate (CaOx) stone formation. The variant sensitivity to CaOx among different rat strains has not been fully explored, although the Wistar rat is known to accumulate more CaOx in kidney tissue after low-dose EG exposure than in the Fischer 344 (F344) rats. Supersaturation of CaOx in tubular fluid contributes to the amount of CaOx crystal formation in the kidney. We hypothesized that the urinary supersaturation of CaOx in Wistar rats is higher than that of F344 rats, thereby allowing for greater CaOx crystal deposition in the Wistar rat. Age-matched male Wistar and F344 rats were treated with 0.75% EG or drinking water for 8 wk. Twenty-four-hour urine was collected at 0, 2, 4, 6, and 8 wk for analysis of key electrolytes to calculate the CaOx supersaturation. Plasma oxalate level was also measured. Our data confirmed the different sensitivity to renal toxicity from EG between the two rat strains (Wistar > F344). After EG treatment, the plasma oxalate level and urine oxalate excretion were markedly greater in the Wistar rats than in the F344 rats, while urine calcium was slightly decreased in Wistars. Thus, the CaOx supersaturation in urine of Wistar rats was higher, which led to a greater crystal deposition in kidney in Wistar rats. These studies suggest that during EG treatment, changes in urine electrolytes and in CaOx supersaturation occur to a greater extent in the Wistar rat, in agreement with its greater sensitivity to EG toxicity.

  3. A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis123

    PubMed Central

    Grigereit, Laura; Pickel, James

    2016-01-01

    Abstract The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells. Upon treating TK rats with the antiviral drug valganciclovir, granule cell neurogenesis can be completely inhibited in adulthood, in both the hippocampus and olfactory bulb. Interestingly, neurogenesis in the glomerular and external plexiform layers of the olfactory bulb was only partially inhibited, suggesting that some adult-born neurons in these regions derive from a distinct precursor population that does not express GFAP. Within the hippocampus, blockade of neurogenesis was rapid and nearly complete within 1 week of starting treatment. Preliminary behavioral analyses indicate that general anxiety levels and patterns of exploration are generally unaffected in neurogenesis-deficient rats. However, neurogenesis-deficient TK rats showed reduced sucrose preference, suggesting deficits in reward-related behaviors. We expect that TK rats will facilitate structural, physiological, and behavioral studies that complement those possible in existing models, broadly enhancing understanding of the function of adult neurogenesis. PMID:27257630

  4. Effect of ageing and oxidative stress on antioxidant enzyme activity in different regions of the rat kidney.

    PubMed

    Thiab, Noor Riyadh; King, Nicola; Jones, Graham L

    2015-10-01

    Oxidative stress has been implicated in ageing and the pathogenesis of chronic kidney disease. We examined levels of antioxidant enzymes glutathione peroxidase, glutathione reductase, glutathione S-transferase, catalase and superoxide dismutase as modulated by age and oxidative stress in different regions of the kidney. Antioxidant enzymes were examined in different regions of the kidney in male Wistar rats. Kidneys from rats of different ages (5, 12, 36 and 60 weeks) were dissected into cortex, outer medulla and inner medulla. Tissues were incubated for 30 min with or without 0.2 mM H2O2 to induce oxidative stress. Antioxidant enzyme activities progressively decreased with age under both control and stress conditions (P < 0.05) after peaking at 12 weeks. Antioxidant enzyme activities were greater in the cortex (P < 0.05) by comparison with the outer and inner medulla, respectively.

  5. Protective effect of Nigella sativa oil on cisplatin induced nephrotoxicity and oxidative damage in rat kidney.

    PubMed

    Farooqui, Zeba; Ahmed, Faizan; Rizwan, Sana; Shahid, Faaiza; Khan, Aijaz Ahmed; Khan, Farah

    2017-01-01

    Nephrotoxicity is a severe complication in patients undergoing cisplatin (CP) chemotherapy. Previous studies in our lab have shown that administration of a single dose of CP results in decrease in the activities of brush border membrane (BBM) and free radical scavenging enzymes and induces oxidative stress in rat kidney. Nigella sativa, is one of the most revered medicinal plant known for its numerous health benefits. Nigella sativa seed/oil has been shown to improve kidney functions in animal models of acute kidney injury. The present study was undertaken to investigate whether Nigella sativa oil (NSO) can prevent the CP-induced nephrotoxic effects. The effect of NSO was determined on CP induced alterations in various serum parameters and on enzymes of carbohydrate metabolism, BBM and antioxidant defense system in renal cortex and medulla. Administration of NSO (2ml/kg bwt. orally), prior to and following a single dose CP treatment (6mg/kg bwt. i.p), significantly attenuated the CP induced increase in serum creatinine (Scr) and blood urea nitrogen (BUN) and decrease in the activities of BBM enzymes in renal cortical and medullary homogenates as well as in isolated BBM vesicles (BBMV). NSO administration also precluded CP induced alterations in the activities of carbohydrate metabolism enzymes and in the enzymatic and non-enzymatic antioxidant parameters. Histopathological observations showed extensive kidney damage in CP treated animals and remarkably reduced renal injury in CP and NSO co-treated group. The biochemical and histological data suggest a protective effect of NSO against CP-induced acute kidney injury. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Methylmalonic acid administration induces DNA damage in rat brain and kidney.

    PubMed

    Andrade, Vanessa M; Dal Pont, Hugo S; Leffa, Daniela D; Damiani, Adriani P; Scaini, Giselli; Hainzenreder, Giana; Streck, Emilio L; Ferreira, Gustavo C; Schuck, Patrícia F

    2014-06-01

    Accumulation of methylmalonic acid (MMA) in tissues and biological fluids is the biochemical hallmark of methylmalonic aciduria. Affected patients present renal failure and severe neurological findings. Considering that the underlying pathomechanisms of tissue damage are not yet understood, in the present work we assessed the in vivo e in vitro effects of MMA on DNA damage in brain and kidney, as well as on p53 and caspase 3 levels, in the presence or absence of gentamicin (acute renal failure model). For in vitro studies, tissue prisms were incubated in the presence of different concentrations of MMA and/or gentamicin for one hour. For in vivo studies, animals received a single injection of gentamicin (70 mg/kg) and/or three injections of MMA (1.67 μmol/g; 11 h interval between injections). The animals were killed 1 h after the last MMA injection. Controls received saline in the same volumes. DNA damage was analyzed by the comet assay. We found that MMA and gentamicin alone or combined in vitro increased DNA damage in cerebral cortex and kidney of rats. Furthermore, MMA administration increased DNA damage in both brain and kidney. Gentamicin per se induced DNA damage only in kidney, and the association of MMA plus gentamicin also caused DNA damage in cerebral cortex and kidney. On the other hand, p53 and caspase 3 levels were not altered by the administration of MMA and/or gentamicin. Our findings provide evidence that DNA damage may contribute to the neurological and renal damage found in patients affected by methylmalonic aciduria.

  7. Mercury inhibits rat liver and kidney glucocorticoid receptor hormone binding activity.

    PubMed

    Brkljacić, J; Vojnović Milutinović, D; Dundjerski, J; Matić, G

    2004-05-01

    The present study was focused on the influence of mercury on the rat liver and kidney glucocorticoid receptor (GR) binding properties. The time-course and dose-dependence of mercury effects, as well as possible involvement of thiol groups were examined after in vivo and in vitro administration of the metal in the form of HgCl2. Mercury led to reduction of the liver and kidney GR hormone binding capacity. In both examined tissues maximal reduction was noticed 4 h after administration of the metal at 2 and 3 mg Hg/kg bw, but the effect was more prominent in kidney as compared to liver. On the other hand, binding affinity in the two tissues was similar. The complete reversal of mercury effects on GR binding capacity by 10 mmol/L DTT was achieved in liver and partially in kidney. The reversal by DTT suggested that mercury caused the decrease of GR binding activity by interacting with thiol groups. The difference in the response of the two tissues reflected the fact that kidney contained a higher mercury concentration and a lower thiol content in comparison to liver. The implicated thiols probably belong to GR, since when applied in vitro at 0 degrees C, mercury produced reduction of the receptor binding activity similar to that observed in vivo. GR protein level examined by quantitative Western blot was either unchanged, when determined by polyclonal antibody, or reduced, when determined by BuGR2 antibody, suggesting that Hg might affect BuGR epitope availability.

  8. Age-related histological changes in kidneys of Brown Norway rat.

    PubMed

    Yabuki, Akira; Yoneshige, Shinichiro; Tanaka, Shin; Tsujio, Masashi; Mitani, Sawane; Yamato, Osamu

    2014-03-01

    In this study, age-dependent histological changes in the kidneys of Brown Norway rat, a strain useful for conducting aging research, were evaluated. Examination was performed at 3, 12, 18, 24 and 30 months of age. Sclerotic and hypertrophic changes of the glomeruli were observed, and quantitative scores of these changes persistently increased with age. A marginal increase in scores was observed for glomerular cystic changes and tubulointerstitial damage. Further, urothelial hyperplasia was observed in the renal papillae, particularly at 30 months of age. In conclusion, the findings of the present study demonstrate that the Brown Norway strain exhibits persistent, but mild progression of age-dependent renal histological changes.

  9. Effect of Different Obesity Phenotypes on Incidence of Chronic Kidney Disease in Tehranian Adults.

    PubMed

    Mottaghi, Azadeh; Mirmiran, Parvin; Delshad, Hossein; Azizi, Fereidoun

    2016-01-01

    The aim of this community-based study is to ascertain the effect of different obesity phenotypes on the incidence of chronic kidney disease in Iranian adults. A prospective cohort study, the Tehran Lipid Glucose Study (TLGS). Adults aged ≥ 20 years with a mean age of 40.38 years (54.8% female) who were free from chronic kidney disease (CKD) at baseline (phase 1) and were followed up at 3 time stages (phases 2, 3, and 4) for a mean duration of 9.4 years to assess the risk for CKD. Obesity phenotypes. Incidence of chronic kidney disease. Glomerular filtration rate (GFR) was estimated from the simplified equation developed using data from the Modification of Diet in Renal Disease (MDRD) Study. CKD events occurred in 1162 participants. The prevalence of the 2 known obesity phenotypes (metabolically obese normal weight [MONW] and metabolically healthy but obese [MHO]) in the overall population was 3.5% and 8.8%, respectively. According to Kaplan-Meier curves, rates of freedom from CKD in the MHO and MONW obesity phenotypes were 75.3% and 60.6%, respectively (p < 0.0001). Age- and sex-adjusted (model 1) hazard ratios for participants with MHO or MONW obesity phenotype were 1.14 (95% confidence interval [CI], 0.91-1.43) and 1.43 (95% CI, 1.09-1.88), respectively. After further adjustment for confounder variables (model 2), multivariate-adjusted hazard ratios for CKD for participants with MHO or MONW obesity phenotypes were 1.23 (95% CI, 0.93-1.62) and 1.43 (95% CI, 1.08-1.90), respectively. Adults with the MONW obesity phenotype compared to those with MHO obesity phenotype have a higher risk for incidence of CKD. The results indicate that having a normal weight is not the only factor to protect against incidence of CKD.

  10. Decrease of FGF receptor (FGFR) and interstitial fibrosis in the kidney of streptozotocin-induced diabetic rats.

    PubMed

    Cheng, M F; Chen, L J; Wang, M C; Hsu, C T; Cheng, J T

    2014-01-01

    Fibrosis is the final disorder of end-stage renal disease. Activation of fibroblast growth factor (FGF) 23-klotho axis could suppress renal fibrosis in mice. Also, a marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats). However, relation of FGF in renal fibrosis remained unclear. This study was aimed to screen the effect of hyperglycemia on FGF receptor (FGFR) and fibrosis in kidney of rats with diabetic nephropathy and investigate this potential mechanism in cultured Madin-Darby Canine Kidney (MDCK) epithelial cells. STZ rats were used to treat with insulin or phloridzin at the dose sufficient to correct hyperglycemia for understanding the changes of renal dysfunction. The cultured MDCK cells were also used to treat with high glucose, hydrogen peroxide, or tiron in addition to transfection of siRNA to silence the klotho. Both insulin and phloridzin reversed fibrosis and FGFR expressions in kidney of STZ rats. It was confirmed in high glucose-exposed MDCK cells. However, klotho failed to modify the level of FGFR in MDCK cells. Meanwhile, FGFR was restored by tiron in MDCK cells and in diabetic rats without changing blood glucose. In conclusion, interstitial fibrosis and decreased FGFR expression are observed in the kidney of diabetic rats. This change is reversed by tiron without the correction of blood glucose. Also, klotho has no effect on expression of FGFR. Thus, decrease of oxidative stress is useful for the recovery of FGFR expression and improvement of renal fibrosis in type-1 like diabetic rats.

  11. Beyond Income: A Social Justice Approach to Assessing Poverty among Older Adults with Chronic Kidney Disease.

    PubMed

    Caplan, Mary A; Washington, Tiffany R; Swanner, Lauren

    2017-01-01

    How social workers define and assess poverty is a matter of economic and social justice. Recent conceptual and measurement advances point to a multidimensional definition of poverty which captures material, social, and political deprivations. Using data from a survey, this article describes how nephrology social workers assess poverty among older adults living with a chronic kidney disease (N = 52). Results suggest respondents already conceive of poverty as a multidimensional experience, support awareness-raising about poverty, and primarily assess poverty by employment status, income, access to transportation, and education. Opportunities to expand poverty assessment in future work are promising.

  12. Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010

    PubMed Central

    Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K.; Kramer, Holly; Rosas, Sylvia E.; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L.

    2016-01-01

    Objective Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. Methods We analyzed data from the NHANES 1999–2010 for 6918 young adults ages 20–40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Results Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6–12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Conclusion Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease. PMID:27224643

  13. Effect of Resveratrol on Leptin and Sirtuin 2 Expression in the Kidneys in Streptozotocin-induced Diabetic Rats.

    PubMed

    Yaylali, Ashi; Ergin, Kemal; Ceçen, Serpil

    2015-08-01

    To investigate the effect of resveratrol (RSV) on the histopathology and leptin and sirtuin 2 expression levels of the kidneys in streptozotocin (STZ)-induced diabetic rats. The study was carried out with 33 young, healthy, female Wistar Albino rats. STZ was given (50 mg/kg, intraperitoneal, single dose) to the rats to induce and constitute a diabetes model. After 1 month of STZ, resveratrol (10 mg/kg) was given for 15 days. Then the kidneys were evaluated histopathologically and the leptin and sirtuin 2 expressions were analyzed immunohistochemically. High glucose and fewer weight levels were seen in the STZ-induced diabetes mellitus group. The glucose levels in the RSV-administered diabetic group showed a tendency to decrease but not significantly. Decreased signs of histopathologic kidney damage was seen in the RSV-administered diabetic group, and an increased expression of leptin was seen in the diabetic kidney tissues. There were no significant differences of sirtuin 2 expression levels among the groups. It was observed that resveratrol caused changes in the diabetic kidney histology and leptin expression level. Resveratrol may be effective, with its antioxidant and antidiabetic effects, in the prevention of kidney damage caused by long-term hyperglycemia.

  14. Maize Purple Plant Pigment Protects Against Fluoride-Induced Oxidative Damage of Liver and Kidney in Rats

    PubMed Central

    Zhang, Zhuo; Zhou, Bo; Wang, Hiaohong; Wang, Fei; Song, Yingli; Liu, Shengnan; Xi, Shuhua

    2014-01-01

    Anthocyanins are polyphenols and well known for their biological antioxidative benefits. Maize purple plant pigment (MPPP) extracted and separated from maize purple plant is rich in anthocyanins. In the present study, MPPP was used to alleviate the adverse effects generated by fluoride on liver and kidney in rats. The results showed that the ultrastructure of the liver and kidney in fluoride treated rats displayed shrinkage of nuclear and cell volume, swollen mitochondria and endoplasmic reticulum and vacuols formation in the liver and kidney cells. MPPP significantly attenuated these fluoride-induced pathological changes. The MDA levels in serum and liver tissue of fluoride alone treated group were significantly higher than those of the control group (p < 0.05). The presence of 5 g/kg MPPP in the diet reduced the elevation of MDA levels in blood and liver, and increased the SOD and GSH-Px activities in kidney and GSH level in liver and kidney compared with the fluoride alone treated group (p < 0.05). In addition, MPPP alleviated the decrease of Bcl-2 protein expression and the increase of Bax protein expression induced by fluoride. This study demonstrated the protective role of MPPP against fluoride-induced oxidative stress in liver and kidney of rats. PMID:24419046

  15. Renoprotective effect of yohimbine on ischaemia/reperfusion-induced acute kidney injury through α2C-adrenoceptors in rats.

    PubMed

    Shimokawa, Takaomi; Tsutsui, Hidenobu; Miura, Takeshi; Nishinaka, Toru; Terada, Tomoyuki; Takama, Masashi; Yoshida, Shuhei; Tanba, Takao; Tojo, Ayumi; Yamagata, Masayo; Yukimura, Tokihito

    2016-06-15

    Excitation of renal sympathetic nervous activity and the resulting increased levels of renal venous norepinephrine play important roles in renal ischaemia/reperfusion injury in rats. This study examined the effects of yohimbine, a non-selective α2-adrenoceptor antagonist, on renal venous norepinephrine levels and kidney function in acute kidney injury. Acute ischaemia/reperfusion-induced kidney injury was induced in rats by clamping the left renal artery and vein for 45min, followed by reperfusion, 2 weeks after a contralateral nephrectomy. Intravenous injection of yohimbine (0.1mg/kg) 5min prior to ischaemia significantly attenuated kidney injury and decreased the renal venous norepinephrine levels, as compared with vehicle-treated rats. To investigate the involvement of α2-adrenoceptor subtypes, we pre-treated with JP-1302, a selective α2C-adrenoceptor antagonist (1mg/kg). This suppressed renal venous norepinephrine levels and tumour necrosis factor-α and monocyte chemoattractant protein-1 mRNA levels after reperfusion and improved kidney function. Pre-treatment with BRL44408, a selective α2A-adrenoceptor antagonist (1mg/kg), or imiloxan, a selective α2B-adrenoceptor antagonist (1mg/kg) had no effect on renal function or tissue injury. These results suggest that yohimbine prevented ischaemia/reperfusion-induced kidney injury by inhibiting α2C-adrenoceptors and suppressing pro-inflammatory cytokine expression.

  16. Primary hyperoxaluria in an adult male: A rare cause of end-stage kidney disease yet potentially fatal if misdiagnosed.

    PubMed

    El-Reshaid, Kamel; Al-Bader, Dalal; Madda, John P

    2016-05-01

    Primary hyperoxaluria is an autosomal recessive disorder due to a deficiency in the activity of the peroxisomal hepatic enzyme alanine-glyoxylate aminotransferase. It is a common cause of urolithiasis and end-stage kidney disease in children contrary to the adult phenotypic presentation which is considered a mild disorder with occasional urolithiasis. In this case report, we describe a 25-year-old man who presented with advanced and irreversible kidney failure within three months following strenuous physical training in the police academy. He had nephrocalcinosis and stones in one kidney. Diagnosis was confirmed by establishing the existence of extensive tubular and interstitial crystal deposition in his kidneys and molecular genetic testing. The case illustrates the need to establish an early diagnosis of this disorder to prevent the need for combined liver and kidney transplantation.

  17. Anemia after kidney transplantation in adult recipients: prevalence and risk factors.

    PubMed

    Einollahi, B; Lessan-Pezeshki, M; Rostami, Z; Kalantar, E; Afshar, R; Beiraghdar, F

    2011-03-01

    To evaluate the prevalence of anemia and appraise its risk factors at 6 months after renal transplantation. This retrospective study was performed between 2008 and 2010 in 2713 adult kidney transplant recipients to determine the prevalence of posttransplantation anemia. Anemia was defined as hemoglobin concentration of 12 g/dL or less in women and 13 g/dL or less in men. The prevalence of posttransplantation anemia was 52.7%, with severe anemia (hemoglobin≤11 g/dL) detected in 24.4% of patients. Impaired renal function was the only risk factor associated with anemia (odds ratio, 3.6; P=.047). However, severe anemia after kidney transplantation was correlated with female sex (P=.001), renal allograft dysfunction (P=.00), and cytomegalovirus infection (P=.002). The present study demonstrated a quite high prevalence of posttransplantation anemia, in particular associated with impaired renal allograft function. Severe anemia was correlated with female sex, degree of kidney graft dysfunction, and cytomegalovirus infection. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Hypoxic preconditioning attenuates lipopolysaccharide-induced oxidative stress in rat kidneys

    PubMed Central

    Yang, Chih-Ching; Ma, Ming-Chieh; Chien, Chiang-Ting; Wu, Ming-Shiou; Sun, Wan-Kuan; Chen, Chau-Fong

    2007-01-01

    Chronic hypoxic (CH) preconditioning reduces superoxide-induced renal dysfunction via the upregulation of superoxide dismutase (SOD) activity and contents. Endotoxaemia reduces renal antioxidant status. We hypothesize that CH preconditioning might protect the kidney from subsequent endotoxaemia-induced oxidative injury. Endotoxaemia was induced by intraperitoneal injection of lipopolysaccharide (LPS; 4 mg kg−1) in rats kept at sea level (SL) and rats with CH in an altitude chamber (5500 m for 15 h day−1) for 4 weeks. LPS enhanced xanthine oxidase (XO) and gp91phox (catalytic subunit of NADPH oxidase) expression associated with burst amount of superoxide production from the SL kidney surface and renal venous blood detected by lucigenin-enhanced chemiluminescence. LPS induced a morphologic-independent renal dysfunction in baseline and acute saline loading stages and increased renal IL-1β protein and urinary protein concentration in the SL rats. After 4 weeks of induction, CH significantly increased Cu/ZnSOD, MnSOD and catalase expression (16 ± 17, 128 ± 35 and 48 ± 21, respectively) in renal cortex, and depressed renal cortex XO (44 ± 16%) and renal cortex (20 ± 9%) and medulla (28 ± 11%) gp91phox when compared with SL rats. The combined effect of enhanced antioxidant proteins and depressed oxidative proteins significantly reduced LPS-enhanced superoxide production, renal XO and gp91phox expression, renal IL-1β production, and urinary protein level. CH also ameliorated LPS-induced renal dysfunction in the baseline and acute saline loading periods. We conclude that CH treatment enhances the intrarenal antioxidant/oxidative protein ratio to overcome endotoxaemia-induced reactive oxygen species formation and inflammatory cytokine release. PMID:17317755

  19. Integrative microRNA-gene expression network analysis in genetic hypercalciuric stone-forming rat kidney

    PubMed Central

    Lu, Yuchao; Qin, Baolong; Hu, Henglong; Zhang, Jiaqiao; Wang, Yufeng; Wang, Qing

    2016-01-01

    Background. MicroRNAs (miRNAs) influence a variety of biological functions by regulating gene expression post-transcriptionally. Aberrant miRNA expression has been associated with many human diseases. Urolithiasis is a common disease, and idiopathic hypercalciuria (IH) is an important risk factor for calcium urolithiasis. However, miRNA expression patterns and their biological functions in urolithiasis remain unknown. Methods and Results. A multi-step approach combining microarray miRNA and mRNA expression profile and bioinformatics analysis was adopted to analyze dysregulated miRNAs and genes in genetic hypercalciuric stone-forming (GHS) rat kidneys, using normal Sprague-Dawley (SD) rats as controls. We identified 2418 mRNAs and 19 miRNAs as significantly differentially expressed, over 700 gene ontology (GO) terms and 83 KEGG pathways that were significantly enriched in GHS rats. In addition, we constructed an miRNA-gene network that suggested that rno-miR-674-5p, rno-miR-672-5p, rno-miR-138-5p and rno-miR-21-3p may play important roles in the regulatory network. Furthermore, signal-net analysis suggested that NF-kappa B likely plays a crucial role in hypercalciuria urolithiasis. Conclusions. This study presents a global view of mRNA and miRNA expression in GHS rat kidneys, and suggests that miRNAs may be important in the regulation of hypercalciuria. The data provide valuable insights for future research, which should aim at validating the role of the genes featured here in the pathophysiology of hypercalciuria. PMID:27069814

  20. Toxic effects of zearalenone on oxidative stress, inflammatory cytokines, biochemical and pathological changes induced by this toxin in the kidney of pregnant rats.

    PubMed

    Jia, Zhiqiang; Liu, Min; Qu, Zhe; Zhang, Yuanyuan; Yin, Shutong; Shan, Anshan

    2014-03-01

    An experiment was conducted to determine the toxic effects of zearalenone (ZEN) on oxidative stress, inflammatory cytokines, biochemical and pathological changes in the kidney of pregnant rats, and to explore the possible mechanism in ZEN induced kidney damage. The rats were fed a normal diet treated with 0.3, 48.5, 97.6 or 146 mg/kg ZEN in feed on gestation days (GDs) 0 through 7, and then all the rats were fed with a normal diet on GDs 8 through 20. The results showed that ZEN induced kidney dysfunction, oxidative damage, pathological changes and increased mRNA and protein expression of TLR4 and inflammatory cytokines in kidney in dose-dependent manner. The results indicated that ZEN caused kidney damage of pregnant rats and TLR4-mediated inflammatory reactions signal pathway was one of the mechanisms of ZEN mediated toxicity in kidney. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Resetting of renal tissular renin-angiotensin and bradykinin-kallikrein systems after unilateral kidney denervation in rats.

    PubMed

    Bohlender, Jürgen M; Nussberger, Jürg; Birkhäuser, Frédéric; Grouzmann, Eric; Thalmann, George N; Imboden, Hans

    2017-02-20

    The renal tissular renin-angiotensin and bradykinin-kallikrein systems control kidney function together with the renal sympathetic innervation but their interaction is still unclear. To further elucidate this relationship, we investigated these systems in rats 6 days after left kidney denervation (DNX, n = 8) compared to sham-operated controls (CTR, n = 8). Plasma renin concentration was unchanged in DNX vs. CTR (p = NS). Kidney bradykinin (BK) and angiotensin (Ang) I and II concentrations decreased bilaterally in DNX vs. CTR rats (~20 to 40%, p < 0.05) together with Ang IV and V concentrations that were extremely low (p = NS). Renin, Ang III and dopamine concentrations decreased by ~25 to 50% and norepinephrine concentrations by 99% in DNX kidneys (p < 0.05) but were unaltered in opposite kidneys. Ang II/I and KA were comparable in DNX, contralateral and CTR kidneys. Ang III/II increased in right vs. DNX or CTR kidneys (40-50%, p < 0.05). Ang II was mainly located in tubular epithelium by immunocytological staining and its cellular distribution was unaffected by DNX. Moreover, the angiotensinergic and catecholaminergic innervation of right kidneys was unchanged vs. CTR. We found an important dependency of tissular Ang and BK levels on the renal innervation that may contribute to the resetting of kidney function after DNX. The DNX-induced peptide changes were not readily explained by kidney KA, renin or plasma Ang I generation. However, tissular peptide metabolism and compartmentalization may have played a central role. The mechanisms behind the concentration changes remain unclear and deserve further clarification.

  2. [Effects of compound Centella asiatica enema on kidneys coefficient, electrolytes and blood in chronic renal failure rats].

    PubMed

    Pang, Lei-lei; Hou, Lian-bing; Mei, Quang-xi; Kong, Xiang-lian; Hu, Ying; Gao, Yu-qiao; Lin, Hui; Liu, Zhao-hui; Zeng, Cong-yan; Lian, Yong-yin; Zhang, Zu-rui

    2010-05-01

    To study the pharmacological effects of compound Centella asiatica enema on chronic renal failure (CRF) rats. Rats were divided into control group, CRF model group, Niaoduqing positive control group, compound Centella asiatica enema high, middle and low three groups kidney coefficient, electrolyte levels, hematocrit (HCT), red blood cell counts (RBC), hemoglobin (HGB) content were observed after 30 days's treatment. Compared with the model group, the level of the electrolyte, HCT, RBC, HGB of rats in compound Centella asiatica enema high-doses group and the Niaoduqing group were significantly improved. High-doses of compound Centella asiatica enema has significant therapeutic effect on CRF rats.

  3. [Function and morphology of isolated rat kidney following cellfree perfusion with various plasmaexpanders (author's transl)].

    PubMed

    Franke, H; Sobotta, E E; Witzki, G; Unsicker, K

    1975-05-01

    Isolated arteficially perfused rat kidneys prepared as described by Franke et al. (1971) were perfused for 60 min with solutions of Haemaccel, Dextran 40, Pluronic-F-108, or hydroxy-aethyl starch in a single pass system. The glomerular filtration rate (GFR) of the Haemaccel or Dextran 40 perfused organs amounted during the first 30 min to 0.58 ml X g-1 X min-1 and 0.47 ml X g-1 X min-1 respectively. Using Pluronic-F-108 or hydroxy-aethyl starch GFR rose to 0.94 ml X g-1 X min-1 and to 0.85 ml X G-1 X min-1. With Haemaccel or Dextran 40 solutions a mean tubular Na-reabsorption of 75.4 mumol X g-1 X min-1 and of 59 mumol X g-1 X min-1 respectively was determined. Employing Pluronic-F-108 or hydroxy-aethyl starch a mean sodium net transport of 92.6 mumol X g-1 X min-1 in both experimental groups was obtained. The differences described in the functional capabilities of Haemaccel or Dextran 40 and of Pluronic-F-108 or Hydroxyethyl starch perfused kidneys are in good accordance with morphological changes in the ultrastructure. The most striking morphological deviations were found in proximal tubules of those kidneys perfused with Haemaccel solutions. On the other hand after perfusion with hydroxyethyl starch only very few morphological alterations could be detected.

  4. Binding and functional effects of atrial natriuretic factor in isolated rat kidney

    SciTech Connect

    Suzuki, M.; Almeida, F.A.; Nussenzveig, D.R.; Sawyer, D.; Maack, T. )

    1987-11-01

    A new methodological approach was developed to study the relationship between specific binding and dose-response curves of the renal effects of atrial natriuretic factor (ANF) in isolated perfused rat kidneys (IK). IK were perfused with {sup 125}I-labeled and unlabeled ANF 1-28 to determine the following: (1) distribution, capacity (C{sub max}), and apparent affinity (S{sub 50}) of specific binding of ANF 1-28 in cortex, outer medulla, and papilla and (2) dose-response curves of the effects of ANF 1-28 on renal hemodynamics and excretion of fluid and electrolytes. The kidney had a very high density of high-affinity binding sites for ANF. Cortex had >90% of total binding sites whereas papilla had <2% of total binding sites with a 10-fold lower apparent affinity than in cortex. ANF-induced increases in glomerular filtration rate and excretion of fluid and electrolytes were detectable at 10-100 pM and maximal effects occurred at 1-10 nM ANF. Below 1 nM there was no dissociation between the renal hemodynamic and natriuretic effects of ANF. There was a close agreement between dose-response and binding curves of ANF to cortex. Results demonstrates that binding site occupancy in kidney cortex and renal effects of ANF occur at near physiological concentrations of the hormone.

  5. Influence of dose on the disposition kinetics of netilmicin in the isolated kidney of the rat.

    PubMed

    Zarzuelo, Aránzazu; Sánchez-Navarro, Amparo; López, Francisco G; Lanao, José M

    2002-01-01

    The disposition of Netilmicin in the isolated rat kidney was studied in order to determine the influence of dose on the drug profile in this tissue. Doses of 50, 200, 800 or 10000 mg were injected through an afferent cannula into the isolated kidney as a bolus injection and outflow perfusate samples were collected. Statistical moments (AUC, MTT, VTT) were estimated from raw outflow curve data. Unit disposition function (UDF) was obtained by mass balance for each studied dose. The results of control assays addressing the viability of the isolated kidney preparations point to a high reproducibility for this preparation under the experimental conditions used, together with an acceptable viability. Comparison of statistical moments and derived parameters such as the extraction coefficient, distribution volume and drug renal clearance (E, Vd, ClE) suggest the existence of modifications in the distribution process with the dose, while elimination seems to remain unvariable; accordingly, the unit disposition function profiles were not superimposed for the different doses but differences during the early and final phases were observed.

  6. Maternal micronutrient deficiency leads to alteration in the kidney proteome in rat pups.

    PubMed

    Ahmad, Shadab; Basak, Trayambak; Anand Kumar, K; Bhardwaj, Gourav; Lalitha, A; Yadav, Dilip K; Chandak, Giriraj Ratan; Raghunath, Manchala; Sengupta, Shantanu

    2015-09-08

    Maternal nutritional deficiency significantly perturbs the offspring's physiology predisposing them to metabolic diseases during adulthood. Vitamin B12 and folate are two such micronutrients, whose deficiency leads to elevated homocysteine levels. We earlier generated B12 and/or folate deficient rat models and using high-throughput proteomic approach, showed that maternal vitamin B12 deficiency modulates carbohydrate and lipid metabolism in the liver of pups through regulation of PPAR signaling pathway. In this study, using similar approach, we identified 26 differentially expressed proteins in the kidney of pups born to mothers fed with vitamin B12 deficient diet while only four proteins were identified in the folate deficient group. Importantly, proteins like calreticulin, cofilin 1 and nucleoside diphosphate kinase B that are involved in the functioning of the kidney were upregulated in B12 deficient group. Our results hint towards a larger effect of vitamin B12 deficiency compared to that of folate presumably due to greater elevation of homocysteine in vitamin B12 deficient group. In view of widespread vitamin B12 and folate deficiency and its association with several diseases like anemia, cardiovascular and renal diseases, our results may have large implications for kidney diseases in populations deficient in vitamin B12 especially in vegetarians and the elderly people.This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidence by autoradiography

    SciTech Connect

    Bouizar, Z.; Rostene, W.H.; Milhaud, G.

    1987-08-01

    In treating age-related osteoporosis and Paget disease of bone, it is of major importance to avoid an escape phenomenon that would reduce effectiveness of the treatment. The factors involved in the loss of therapeutic efficacy with administration of large pharmacological doses of the hormone require special consideration. Down-regulation of the hormone receptors could account for the escape phenomenon. Specific binding sites for salmon calcitonin (sCT) were characterized and localized by autoradiography on rat kidney sections incubated with /sup 125/I-labeled sCT. Autoradiograms demonstrated a heterogeneous distribution of /sup 125/I-labeled sCT binding sites in the kidney, with high densities in both the superficial layer of the cortex and the outer medulla. Infusion of different doses of unlabeled sCT by means of Alzet minipumps for 7 days produced rapid changes in plasma calcium, phosphate, and magnesium levels, which were no longer observed after 2 or 6 days of treatment. Besides, infusion of high doses of sCT induced down-regulation of renal sCT binding sites located mainly in the medulla, where calcitonin (CT) has been shown to exert it physiological effects on water and ion reabsorption. These data suggest that the resistance to high doses of sCT often observed during long-term treatment of patients may be the consequence of not only bone-cell desensitization but also down-regulation of CT-sensitive kidney receptor sites.

  8. Simultaneous liver-kidney transplantation for adult recipients with irreversible end-stage renal disease.

    PubMed

    Moreno-Gonzalez, E; Meneu-Diaz, J C; Garcia, I; Perez Cerdá, F; Abradelo, M; Jimenez, C; Loinaz, C; Gomez, R; Gimeno, A; Moreno, A

    2004-11-01

    Combined liver-kidney transplantation is safe (low morbidity and acceptable mortality) and effective in patients with end-stage liver disease. Although refinements in surgical technique have resulted in better patient and allograft outcomes, the negative impact of renal insufficiency on survival in patients undergoing liver transplantation has been widely reported, although some aspects are controversial. Analysis of the clinical characteristics and outcome in the management of patients undergoing combined liver-kidney transplantation. The end points were operative mortality, morbidity, and long-term survival. University Hospital 12 de Octubre. Between May 1986 and December 2001, 820 liver transplantations were performed. There were 16 cases (1.96%) of combined liver-kidney transplantations, which represent the sample of this study. Mean +/- SD follow-up of 42.2 +/- 29 months: 6 patients died (37.5% mortality rate). There were 4 (25%) hospital deaths within 6 months following surgery and 2 after 6 months (4 sepsis, 1 refractory heart failure, and 1 recurrent hepatitis C virus disease). Univariate analysis related to mortality included age, sex, etiology, preoperative creatinine level, United Network for Organ Sharing status, Child-Pugh score, type of hepatectomy (piggyback), intraoperative blood product administration, and the presence of postoperative complications. The only 2 significant factors were the presence of postoperative complications (P = .01) and the United Network for Organ Sharing status (P = .02). Crude survival rate was 62.5%. Actuarial survival rates were 80%, 71%, and 60% at 1, 3, and 5 years, respectively. Because end-stage renal disease is not a formal contraindication for liver transplantation, a combined liver-kidney transplantation for adults with end-stage renal disease can be done safely and effectively.

  9. Kidney function and cognitive health in older adults: the Cardiovascular Health Study.

    PubMed

    Darsie, Brendan; Shlipak, Michael G; Sarnak, Mark J; Katz, Ronit; Fitzpatrick, Annette L; Odden, Michelle C

    2014-07-01

    Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFRcys). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFRcys and change in cognitive function after adjustment for confounders; persons with an eGFRcys of less than 60 mL/minute/1.73 m(2) had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFRcys of 90 or more mL/minute/1.73 m(2). Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFRcys of less than 60 mL/minute/1.73 m(2) had fewer cognitive impairment-free life-years on average compared with those with eGFRcys of 90 or more mL/minute/1.73 m(2), independent of confounders and mediating cardiovascular events (mean difference = -0.44, 95% confidence interval: -0.62, -0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function.

  10. Kidney Function and Cognitive Health in Older Adults: The Cardiovascular Health Study

    PubMed Central

    Darsie, Brendan; Shlipak, Michael G.; Sarnak, Mark J.; Katz, Ronit; Fitzpatrick, Annette L.; Odden, Michelle C.

    2014-01-01

    Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C–based estimated glomerular filtration rate (eGFRcys). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFRcys and change in cognitive function after adjustment for confounders; persons with an eGFRcys of less than 60 mL/minute/1.73 m2 had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFRcys of 90 or more mL/minute/1.73 m2. Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFRcys of less than 60 mL/minute/1.73 m2 had fewer cognitive impairment–free life-years on average compared with those with eGFRcys of 90 or more mL/minute/1.73 m2, independent of confounders and mediating cardiovascular events (mean difference = −0.44, 95% confidence interval: −0.62, −0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function. PMID:24844846

  11. Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats

    PubMed Central

    Kieffer, Dorothy A.; Piccolo, Brian D.; Vaziri, Nosratola D.; Liu, Shuman; Lau, Wei L.; Khazaeli, Mahyar; Nazertehrani, Sohrab; Moore, Mary E.; Marco, Maria L.; Martin, Roy J.

    2016-01-01

    Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function. PMID:26841824

  12. Telmisartan ameliorates fibrocystic liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease.

    PubMed

    Yoshihara, Daisuke; Kugita, Masanori; Sasaki, Mai; Horie, Shigeo; Nakanishi, Koichi; Abe, Takaaki; Aukema, Harold M; Yamaguchi, Tamio; Nagao, Shizuko

    2013-01-01

    Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the

  13. Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats.

    PubMed

    Kieffer, Dorothy A; Piccolo, Brian D; Vaziri, Nosratola D; Liu, Shuman; Lau, Wei L; Khazaeli, Mahyar; Nazertehrani, Sohrab; Moore, Mary E; Marco, Maria L; Martin, Roy J; Adams, Sean H

    2016-05-01

    Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function.

  14. Telmisartan Ameliorates Fibrocystic Liver Disease in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

    PubMed Central

    Yoshihara, Daisuke; Kugita, Masanori; Sasaki, Mai; Horie, Shigeo; Nakanishi, Koichi; Abe, Takaaki; Aukema, Harold M.; Yamaguchi, Tamio; Nagao, Shizuko

    2013-01-01

    Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the

  15. Dual Kidney Allocation Score: A Novel Algorithm Utilizing Expanded Donor Criteria for the Allocation of Dual Kidneys in Adults.

    PubMed

    Johnson, Adam P; Price, Thea P; Lieby, Benjamin; Doria, Cataldo

    2016-09-08

    BACKGROUND Dual kidney transplantation (DKT) of expanded-criteria donors is a cost-intensive procedure that aims to increase the pool of available deceased organ donors and has demonstrated equivalent outcomes to expanded-criteria single kidney transplantation (eSKT). The objective of this study was to develop an allocation score based on predicted graft survival from historical dual and single kidney donors. MATERIAL AND METHODS We analyzed United Network for Organ Sharing (UNOS) data for 1547 DKT and 26 381 eSKT performed between January 1994 and September 2013. We utilized multivariable Cox regression to identify variables independently associated with graft survival in dual and single kidney transplantations. We then derived a weighted multivariable product score from calculated hazard ratios to model the benefit of transplantation as dual kidneys. RESULTS Of 36 donor variables known at the time of listing, 13 were significantly associated with graft survival. The derived dual allocation score demonstrated good internal validity with strong correlation to improved survival in dual kidney transplants. Donors with scores less than 2.1 transplanted as dual kidneys had a worsened median survival of 594 days (24%, p-value 0.031) and donors with scores greater than 3.9 had improved median survival of 1107 days (71%, p-value 0.002). There were 17 733 eSKT (67%) and 1051 DKT (67%) with scores in between these values and no differences in survival (p-values 0.676 and 0.185). CONCLUSIONS We have derived a dual kidney allocation score (DKAS) with good internal validity. Future prospective studies will be required to demonstrate external validity, but this score may help to standardize organ allocation for dual kidney transplantation.

  16. Kidney injury biomarkers and urinary creatinine variability in nominally healthy adults.

    PubMed

    Stiegel, M A; Pleil, J D; Sobus, J R; Angrish, M M; Morgan, M K

    2015-01-01

    Environmental exposure diagnostics use creatinine concentrations in urine aliquots as the internal standard for dilution normalization of all other excreted metabolites when urinary excretion rate data are not available. This is a reasonable approach for healthy adults as creatinine is a human metabolite that is continually produced in skeletal muscles and presumably excreted in the urine at a stable rate. However, creatinine also serves as a biomarker for glomerular filtration rate (efficiency) of the kidneys, so undiagnosed kidney function impairment could affect this commonly applied dilution calculation. The United States Environmental Protection Agency (US EPA) has recently conducted a study that collected approximately 2600 urine samples from 50 healthy adults, aged 19-50 years old, in North Carolina in 2009-2011. Urinary ancillary data (creatinine concentration, total void volume, elapsed time between voids), and participant demographic data (race, gender, height, and body weight) were collected. A representative subset of 280 urine samples from 29 participants was assayed using a new kidney injury panel (KIP). In this article, we investigated the relationships of KIP biomarkers within and between subjects and also calculated their interactions with measured creatinine levels. The aims of this work were to document the analytical methods (procedures, sensitivity, stability, etc.), provide summary statistics for the KIP biomarkers in "healthy" adults without diagnosed disease (distribution, fold range, central tendency, variance), and to develop an understanding as to how urinary creatinine level varies with respect to the individual KIP proteins. Results show that new instrumentation and data reduction methods have sufficient sensitivity to measure KIP levels in nominally healthy urine samples, that linear regression between creatinine concentration and urinary excretion explains only about 68% of variability, that KIP markers are poorly correlated with

  17. Acute effects of grayanotoxin in rhododendron honey on kidney functions in rats.

    PubMed

    Silici, S; Doğan, Z; Sahin, H; Atayoğlu, T; Yakan, B

    2016-02-01

    The aim of the study is to evaluate the acute biochemical and histological changes in rat kidneys after treatment with grayanotoxin (GTX) of rhododendron honey (RH). A total of 60 Sprague-Dawley female rats were divided into five groups of 12 rats each, one being a control group (group 1) and group 2 was treated with 0.015 mg/kg/bw of GTX standard preparation via intraperitoneal injection. Groups 3, 4, and 5 were given RH at doses of 0.1, 0.5, and 2.5 g/kg/bw, respectively, via oral gavage. Compared to the control group, significant increases were observed in glucose, blood urea nitrogen (BUN), and creatinine levels of the GTX-injected groups after 1 h. However, in low dose RH group, such an increase was not observed and had a normal appearance histologically. Therefore, low dose (1 g/kg/bw) of RH produces no acute adverse effects on renal functions of rats.

  18. Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

    PubMed Central

    Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

    2016-01-01

    The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. PMID:27466399

  19. Intracellular penetration and accumulation of radiographic contrast media in the rat kidney

    SciTech Connect

    Nordby, A.; Tvedt, K.E.; Halgunset, J.; Haugen, O.A. )

    1990-09-01

    Radiographic iodine-containing contrast media (meglumine calcium metrizoate, iohexol and meglumine sodium ioxaglate) were injected intravenously in rats. At various intervals after exposure, in situ cryofixation of kidneys was performed. Thin, freeze-dried cryosections were examined by electron microscopy and X-ray microanalysis. In endothelial cells, erythrocytes and tubular cells high dry weight concentrations of iodine were found. Twenty-four hours after iohexol was injected, no trace of iodine was found in the plasma, microvilli or the nuclei of the tubular cells. Small organelle-like compartments in the cytoplasm of the proximal tubular cells contained high concentrations of iodine, whereas no iodine was found in the surrounding cytoplasm. Since no metabolism of contrast medium has been demonstrated, the iodine signals must be emitted from contrast medium molecules. Other elements were also measured, with the concentrations being always within the ranges found in tubular cells of control animals. The detection of intracellular contrast thus does not seem to be an artifact due to cell injury, but rather represents a physiological event in healthy cells in the rat kidney. Our results are in contradiction to the prevailing opinion that contrast media do not enter healthy cells. However, previous conclusions have been based on the use of conventional preparation methods, and the highly water soluble contrast molecules may have been lost during the different steps of fixation and processing.

  20. Guidelines for prevention and management of complications following kidney transplantation in rats.

    PubMed

    Pahlavan, P S; Mehrabi, A; Kashfi, A; Soleimani, M; Fani-Yazdi, S H; Schemmer, P; Gutt, C N; Friess, H; Weitz, J; Kraus, Th W; Büchler, M W; Schmidt, J

    2005-06-01

    Kidney transplantation in rats is a useful model for microsurgery, transplantation, and immunology studies. Our aim was to analyze various techniques of kidney transplantation in rats with emphasis on guidelines for the prevention and management of complications. Complications were categorized into general, vascular, and urological types and respectively attributed to long transplantation time, core body temperature drop, nonreplaced intraoperative blood loss, anastomosis failure, and ureteral anastomoses with stents or cannulas, which increase the risk of calculus formation. In conclusion, to decrease the complication rates the animal should be placed on a heating pad. For hemodynamic stability NaCl should be administered subcutaneously. To reduce the risk of thrombosis, ice-cold saline containing heparin should be administered. Vascular complications, which mainly depend on the microsurgeon's expertise, can be prevented by meticulous surgical technique (preferably an end-in-end anastomosis). The main urinary complications ca