Increased Serum Blood Urea Nitrogen Research Articles

A novel web-based calculator to predict 30-day all-cause in-hospital mortality for 7,202 elderly patients with heart failure in ICUs: a multicenter retrospective cohort study in the United States.

Heart failure (HF) is a significant cause of in-hospital mortality, especially for the elderly admitted to intensive care units (ICUs). This study aimed to develop a web-based calculator to predict 30-day in-hospital mortality for elderly patients with HF in the ICU and found a relationship between risk factors and the predicted probability of death. Data (N = 4450) from the MIMIC-III/IV database were used for model training and internal testing. Data (N = 2,752) from the eICU-CRD database were used for external validation. The Brier score and area under the curve (AUC) were employed for the assessment of the proposed nomogram. Restrictive cubic splines (RCSs) found the cutoff values of variables. The smooth curve showed the relationship between the variables and the predicted probability of death. A total of 7,202 elderly patients with HF were included in the study, of which 1,212 died. Multivariate logistic regression analysis showed that 30-day mortality of HF patients in ICU was significantly associated with heart rate (HR), 24-h urine output (24h UOP), serum calcium, blood urea nitrogen (BUN), NT-proBNP, SpO2, systolic blood pressure (SBP), and temperature (P < 0.01). The AUC and Brier score of the nomogram were 0.71 (0.67, 0.75) and 0.12 (0.11, 0.15) in the testing set and 0.73 (0.70, 0.75), 0.13 (0.12, 0.15), 0.65 (0.62, 0.68), and 0.13 (0.12, 0.13) in the external validation set, respectively. The RCS plot showed that the cutoff values of variables were HR of 96 bmp, 24h UOP of 1.2 L, serum calcium of 8.7 mg/dL, BUN of 30 mg/dL, NT-pro-BNP of 5121 pg/mL, SpO2 of 93%, SBP of 137 mmHg, and a temperature of 36.4°C. Decreased temperature, decreased SpO2, decreased 24h UOP, increased NT-proBNP, increased serum BUN, increased or decreased SBP, fast HR, and increased or decreased serum calcium increase the predicted probability of death. The web-based nomogram developed in this study showed good performance in predicting 30-day in-hospital mortality for elderly HF patients in the ICU.

Relationship between serum biochemical parameters and kidney lesions in broiler chickens with acute tubular necrosis

To evaluate the effectiveness of biochemical factors such as blood urea nitrogen (BUN), creatinine, and serum uric acid in identifying and diagnosing acute tubular necrosis lesion in broilers, kidney tissue and blood samples from 80 broiler chickens at the slaughter stage were collected. Tissue samples were collected in 10% formalin to detect pathological lesions. The components of BUN, creatinine, and serum uric acid were measured with commercially available kits. After preparing the histopathological sections, based on the percentage of necrosis of the kidney tubules in each tissue sample, the pathological lesions were divided into 3 degrees: mild, moderate, and severe. The results showed that 36 samples out of 80 samples (45%) had acute tubular necrosis (ATN) lesions; 14 (17.5%), 12 (15%), and 10 (12.5%) samples had severe, moderate, and mild tubular necrosis lesions, respectively. The amount of uric acid in chickens with moderate and severe lesions showed a significant difference with the chickens without lesions and the mild lesion. However, BUN and creatinine increased significantly only in severe ATN lesions. In general, the results of this study state that severe lesions of renal tubules are associated with an increase in serum BUN, creatinine, and uric acid, but in moderate lesions, only uric acid may increase. Therefore, according to the results of this study, uric acid can be considered as a diagnostic biomarker in moderate to severe ATN.

Protective effect of fatty acid amide hydrolase inhibitor URB597 and monoacylglycerol lipase inhibitor KML29 on renal ischemia-reperfusion injury via toll-like receptor 4/nuclear factor-kappa B pathway.

Arachidonoyl ethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) are the most studies endocannabinoids. AEA and 2-AG are degraded by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes, respectively. FAAH and MAGL enzymes are widely expressed in many tissues, including kidney. Recent works have depicted that AEA and 2-AG levels are associated with ischemia-reperfusion (IR) injury. In this study, we investigated the effects of MAGL inhibitor KML29 and FAAH inhibitor URB597 against kidney IR injury. The kidneys of the rats underwent ischemia for 45min and then reperfusion for 24h. KML29 and URB597 were administered intraperitoneally with kidney IR to two different treatment groups. IR application increased serum blood urea nitrogen (BUN), creatinine (Cre), interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels, while these parameters were decreased following KML29 and URB597 administration. KML29 and URB597 administration also reduced the increased toll-like receptor-4 (TRL-4), phosphorylated-NF-κB, phosphorylated-IκB-α, tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), caspase-3 levels and histopathological damage in kidney tissue. Our results reveal that MAGL inhibitor KML29 and FAAH inhibitor URB597 have a protective effect on kidney IR injury by preventing apoptosis and inflammation. Inhibition of MAGL and FAAH may be a new therapeutic strategy to prevent kidney IR injury.

Eucalyptol alleviates cisplatin-induced kidney damage in rats

This study was aimed to explore the therapeutic effect of eucalyptol on cisplatin induced kidney damage in Wistar albino rats. The animals were divided into four groups: sham (S), eucalyptol (E), cisplatin (C), and cisplatin + eucalyptol (CE) randomly, six animals in each group. Groups C and CE were received cisplatin (12 mg/kg, a single dose, intraperitoneally (i.p.)). Groups E and CE were treated with eucalyptol (100 mg/kg, for seven days, orally). The blood samples and kidney tissues were collected following sacrification and analyzed histopathologically and biochemically. Histopathological results revealed tubular degeneration and necrosis, inflammatory cell infiltration, tubular lumen dilatation, enlargement of bowman’s space and hyaline cast were significantly irregular in the group C than group S. However, eucalyptol treatment (CE) modulated the alterations in the group C. Serum levels of blood urea nitrogen (BUN) and creatinine (CRE) were considerably higher in the group C compared to the other groups. There was no significant difference among the other groups statistically (except group C) in terms of BUN and CRE values. Eucalyptol treatment (at 100 mg/kg, for seven days) decreased the cisplatin induced increase in serum BUN and CRE levels and restored the reduced Vit C level and CAT activity of kidneys caused by cisplatin. Thus, eucalyptol’s antioxidative, nephroprotective, and curative effects indicated the potential for future drug development.

Screening for polystyrene nanoparticle toxicity on kidneys of adult male albino rats using histopathological, biochemical, and molecular examination results

Polystyrene Nanoparticles (PS-NPs) used for packaging foam, disposable cups, and food containers. Therefore, this study aimed to evaluate PS- NPs toxic effects on kidney of adult male albino rats. A total of 30 rats divided into three groups (n = 10): group I negative control group; group II orally administered 3% PS-NPs (3 mg/kg body weight/day) and group III orally administered 3% PS-NPs (10 mg/kg body weight/day) for 35 days. Blood and kidney samples collected and processed for biochemical, histopathological, and immunohistochemical examinations. Results showed that low and high doses PS-NPs had significantly increased serum blood urea nitrogen (BUN), creatinine, malondialdehyde, significantly further reduced glutathione, downregulation of nuclear factor erythroid 2–related factor 2 and glutathione peroxidase, upregulation of caspase-3 and Cytochrome-c. Histopathological examination revealed several alterations. Low dose of PS-NPs exhibited dilated glomerular capillaries, hypotrophy of some renal corpuscles significantly decreases their diameter to 62 μm. Some proximal convoluted tubules and distal convoluted tubules showed loss of cellular architecture with pyknotic nuclei. Hyalinization and vacuolation in renal medulla. In high dose PS-NPs, alterations increased in severity. A significant increase in percentage area of cyclooxygenase-2 in low and high-doses. In conclusion, PS-NPs are a nephrotoxic causing renal dysfunction.

COVID-19 and renal involvement in children: a retrospective study.

Background:The New coronavirus (SARS COV-2) can cause acute respiratory disease and also multiorgan dysfunction. There is insufficient data about kidney involvement in children. So, this study was done on children with COVID-19 to evaluate nephrological involvement.Methods:All children with confirmed or suspected COVID-19 who were admitted in Children Hospital .were enrolled. They were admitted in hospital from March 2020 to July 2020. Serum Blood Urea Nitrogen (BUN), creatinine, sodium, potassium, calcium and urinalysis were evaluated. Also, glomerular filtration rate (GFR) was calculated by Schertz's formula. All patients were evaluated by chest x-ray and/or computerized tomography scanning (CTS). The data were analyzed by SPSS software and P value less than 0.05 was determined as significant.Results:Forty-seven children with confirmed or suspected COVID-19 were enrolled to this study. At admission, 23.4% and 27.7% of children with COVID-19 infection had abnormal increase in serum BUN and creatinine, respectively. Also 78.8% and 25.5% of children had GFR less than 90 and 60 ml/min /1.732, respectively. Additionally, 13/47 (27.7%) of children had abnormal urine analysis (microscopic hematuria and/or proteinuria). There wasn’t a significant relationship between pulmonary lesions and abnormal reduction of GFR (P<0/05).Conclusion:In the study, the risk of AKI (acute kidney injury) and decrease of GFR and also abnormal urinalysis is high in children with COVID-19. So, more attention for detection of kidney involvement is necessary and more conservative management for prevention of AKI and decrease of GFR are recommended.

Simulation, In Vitro, and In Vivo Cytotoxicity Assessments of Methotrexate-Loaded pH-Responsive Nanocarriers.

In this study, pH-responsive niosomal methotrexate (MTX) modified with ergosterol was prepared for potential anticancer application. The prepared formulation had a size of 176.7 ± 3.4 nm, zeta potential of −31.5 ± 2.6 mV, EE% of 76.9 ± 2.5%, and a pH-responsive behavior in two different pHs (5.4 and 7.4). In-silico evaluations showed that MTX intended to make a strong hydrogen bond with Span 60 compartments involving N2 and O4 atoms in glutamic acid and N7 atom in pteridine ring moieties, respectively. The cytotoxic effects of free and pH-MTX/Nio were assessed against MCF7 and HUVECs. Compared with free MTX, we found significantly lower IC50s when MCF7 cells were treated with niosomal MTX (84.03 vs. 9.464 µg/mL after 48 h, respectively). Moreover, lower cell killing activity was observed for this formulation in normal cells. The pH-MTX/Nio exhibited a set of morphological changes in MCF7 cells observed during cell death. In-vivo results demonstrated that intraperitoneal administration of free MTX (2 mg/kg) after six weeks caused a significant increase in serum blood urea nitrogen (BUN), serum creatinine, and serum malondialdehyde (MDA) levels of rats compared to the normal control rats. Treatment with 2 and 4 mg/kg doses of pH-MTX/Nio significantly increased serum BUN, serum creatinine, and serum lipid peroxidation. Still, the safety profile of such formulations in healthy cells/tissues should be further investigated.

Comparing the Histopathological Effects of Selenium Nanoparticles and Selenium Nanocomposites in Rat Models

Background: Selenium nanoparticles (Se NPs) and selenium nanocomposites (Se NCs) have different biological effects. The current study aimed to compare the effects of newly synthesized Se NPs and Se NCs on biochemical and histopathological parameters of rats. The synthesized Se NPs were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray analysis (EDAX), and scanning electron microscopy (SEM) techniques. Materials and Methods: Adult male Wistar rats were divided into four equal groups to examine the biological effects of Se NPs. Control rats received saline intraperitoneally while experimental rats were received four-week intraperitoneal injections of Se powder, Se NPs, and Se NCs at the dose of (0.4 mg/kg). After four weeks, serum was obtained by the conventional methods, and then rats were sacrificed to separate liver, kidney, and testis tissues for histopathological examinations. Results: The intraperitoneal injection of Se powder caused significant elevations in serum liver enzyme levels, serum blood urea nitrogen (BUN) lipid peroxidation, and serum creatinine levels (P&lt;0.05). The histopathological investigations showed necrosis and fatty change in liver. Kidney sections showed cytoplasmic vacuolation and hyaline casts, and the testis sections showed degeneration of seminiferous tubules. Se NPs intraperitoneal injections at a dose of 0.4 mg/kg caused no significant effects on liver enzymes, malondialdehyde (MDA) content, and histopathological changes while significantly increased serum BUN and creatinine levels (P&lt;0.05). The group treated with Se NCs showed normal biochemical and histopathological parameters (P&lt;0.05). Conclusion: The current study proved the toxicity of Se powder; however, nano-formulations of Se showed fewer side effects.

MO342ADMINISTRATION OF ASTRAGALUS MEMBRANACEUS PREVENTED CISPLATIN-INDUCED AKI, ESPECIALLY IN OLD MICE

Abstract Background and Aims Recent findings suggest that acute kidney injury (AKI), which occurs frequently but is believed to be completely reversible, is an important factor driving chronic kidney disease (CKD) pathogenesis or progression. We have investigated Astragalus membranaceus (AM), which has been shown to have various pharmacological effects on several organs (see http://nccih.nih.gov/health/astragalus). However, up to now, little evidence of its effectiveness against CKD has been provided. We hypothesized that AM could target AKI and that sustainable prevention of AKI by AM might delay pathogenesis and progression of CKD. Here we focused on AKI as a promoter of CKD progression in order to examine the effects of AM histologically and histochemically in mice. Method Here we used two groups of female C57BL/6 mice: one that was aged 12 weeks and one that was aged 52 weeks. After the first blood collection (of approximately 0.2 ml), the two age groups of mice were administered AM powder mixed with sterilized 0.5% methylcellulose 400 (w/v) (the AM-administered group) or sterilized 0.5% methylcellulose 400 (the control group), respectively. Two hours after the administration, 0.5 mg/ml cisplatin (20 mg/kg or 14 mg/kg) or 0.9% NaCl were injected intraperitoneally. Three days after injection, blood was collected and kidneys were harvested. We measured blood urea nitrogen (BUN) and creatinine (CRE) to detect AKI, and assessed histological change in dissected kidney sections stained with Hematoxylin-Eosin and Periodic acid-Schiff and histochemical change in sections stained with anti-CD3 and anti-CD68 antibodies. Generally, 20 mg/kg cisplatin was used to induce AKI in the experimental model. Results Injection with 20 mg/kg cisplatin was shown to induce AKI pathology in young mice and shorten survival in old mice, and AM administration was unable to improve AKI pathology in young mice or survival in old mice. Next, we injected mice in both age groups with 14 mg/kg cisplatin. We found that this dose significantly increased serum BUN or CRE and caused histological damage in renal tubule epithelial cells and glomeruli in old mice but not in young mice, which showed no pathological change. And Astragalus treatment in advance almost totally prevented these pathological changes in old mice. The AKI generated in old mice with 14 mg/kg of cisplatin was significantly normalized by pretreatment with AM. Next, histochemical analysis of renal CD3- and CD68-positive cells revealed both were increased in the murine AKI model induced by injection with 20 mg/kg cisplatin. Interestingly, in old mice, 14 mg/kg cisplatin-AKI increased CD3-positive cells but not CD68-positive cells. These findings suggest that AM may improve daily minor disturbances, such as AKI, that cause pathogenesis and progression of CKD especially in old age. Conclusion AM administration, at least in part, can reduce day-to-day AKI occurrence, but is ineffective in young kidneys. However, sustained use of AM could play a critical role in prolonging the activity of aged kidneys. Acknowledgments We thank the Education and Research Support Center, Tokai University, for technical assistance. This work was supported by a grant from the Japan Society for Promotion of Science JSPS KAKENHI KIBAN-C (Grant Number 16K09259) and by Tokai university general research organization grant.

Assessment of SnFe2O4 Nanoparticles for Potential Application in Theranostics: Synthesis, Characterization, In Vitro, and In Vivo Toxicity.

In this research, tin ferrite (SnFe2O4) NPs were synthesized via hydrothermal route using ferric chloride and tin chloride as precursors and were then characterized in terms of morphology and structure using Fourier-transform infrared spectroscopy (FTIR), Ultraviolet–visible spectroscopy (UV-Vis), X-ray power diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), and Brunauer–Emmett–Teller (BET) method. The obtained UV-Vis spectra was used to measure band gap energy of as-prepared SnFe2O4 NPs. XRD confirmed the spinel structure of NPs, while SEM and TEM analyses disclosed the size of NPs in the range of 15–50 nm and revealed the spherical shape of NPs. Moreover, energy dispersive X-ray spectroscopy (EDS) and BET analysis was carried out to estimate elemental composition and specific surface area, respectively. In vitro cytotoxicity of the synthesized NPs were studied on normal (HUVEC, HEK293) and cancerous (A549) human cell lines. HUVEC cells were resistant to SnFe2O4 NPs; while a significant decrease in the viability of HEK293 cells was observed when treated with higher concentrations of SnFe2O4 NPs. Furthermore, SnFe2O4 NPs induced dramatic cytotoxicity against A549 cells. For in vivo study, rats received SnFe2O4 NPs at dosages of 0, 0.1, 1, and 10 mg/kg. The 10 mg/kg dose increased serum blood urea nitrogen and creatinine compared to the controls (P < 0.05). The pathology showed necrosis in the liver, heart, and lungs, and the greatest damages were related to the kidneys. Overall, the in vivo and in vitro experiments showed that SnFe2O4 NPs at high doses had toxic effects on lung, liver and kidney cells without inducing toxicity to HUVECs. Further studies are warranted to fully elucidate the side effects of SnFe2O4 NPs for their application in theranostics.

Epstein-Barr Functional Mimicry: Pathogenicity of Oncogenic Latent Membrane Protein-1 in Systemic Lupus Erythematosus and Autoimmunity.

Systemic lupus erythematosus (SLE) and other autoimmune diseases are propelled by immune dysregulation and pathogenic, disease-specific autoantibodies. Autoimmunity against the lupus autoantigen Sm is associated with cross-reactivity to Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1). Additionally, EBV latent membrane protein-1 (LMP1), initially noted for its oncogenic activity, is an aberrantly active functional mimic of the B cell co-stimulatory molecule CD40. Mice expressing a transgene (Tg) for the mCD40-LMP1 hybrid molecule (containing the cytoplasmic tail of LMP1) have mild autoantibody production and other features of immune dysregulation by 2–3 months of age, but no overt autoimmune disease. This study evaluates whether exposure to the EBV molecular mimic, EBNA-1, stimulates antigen-specific and concurrently-reactive humoral and cellular immunity, as well as lupus-like features. After immunization with EBNA-1, mCD40-LMP1 Tg mice exhibited enhanced, antigen-specific, cellular and humoral responses compared to immunized WT congenic mice. EBNA-1 specific proliferative and inflammatory cytokine responses, including IL-17 and IFN-γ, were significantly increased (p<0.0001) in mCD40-LMP1 Tg mice, as well as antibody responses to amino- and carboxy-domains of EBNA-1. Of particular interest was the ability of mCD40-LMP1 to drive EBNA-1 associated molecular mimicry with the lupus-associated autoantigen, Sm. EBNA-1 immunized mCD40-LMP1 Tg mice exhibited enhanced proliferative and cytokine cellular responses (p<0.0001) to the EBNA-1 homologous epitope PPPGRRP and the Sm B/B’ cross-reactive sequence PPPGMRPP. When immunized with the SLE autoantigen Sm, mCD40-LMP1 Tg mice again exhibited enhanced cellular and humoral immune responses to both Sm and EBNA-1. Cellular immune dysregulation with EBNA-1 immunization in mCD40-LMP1 Tg mice was accompanied by enhanced splenomegaly, increased serum blood urea nitrogen (BUN) and creatinine levels, and elevated anti-dsDNA and antinuclear antibody (ANA) levels (p<0.0001 compared to mCD40 WT mice). However, no evidence of immune-complex glomerulonephritis pathology was noted, suggesting that a combination of EBV and genetic factors may be required to drive lupus-associated renal disease. These data support that the expression of LMP1 in the context of EBNA-1 may interact to increase immune dysregulation that leads to pathogenic, autoantigen-specific lupus inflammation.

Blood urea nitrogen level in patients with chronic total occlusion predicts long-term mortality independent of estimated glomerular filtration rate and serum creatine level: (9-year follow-up results)

Aim: Increased serum blood urea nitrogen (BUN) level is an indicator of neurohormonal and renal dysfunction, and is associated with the major adverse cardiovascular events (MACE). Chronic total occlusion (CTO) is a typical coronary artery disease diagnosed by coronary angiography. We established and tested the hypothesis that there might be a relationship between serum BUN level and long-term prognosis in patients with CTO.Materials and Methods: The study consisted of 124 patients diagnosed with CTO. The patients were followed up for a mean of 9.2 (7.4-9.5) years, and all-cause mortality was determined.Results: Patients were divided into two groups according to mortality outcome. During the follow-up, 38 of 124 patients died. Univariate Cox analysis showed that age (p=0.002), BUN (p=0.001), and serum creatinine levels (p=0.039) were associated with mortality. BUN level (OR: 1.074; 95% CI: 1.018-1.134; p=0.009) and age (OR: 1.043; 95% CI: 1.001-1.087, p=0.043) were independently associated with mortality in multivariate Cox analysis. In the ROC analysis, the AUC values for BUN and estimated glomerular filtration rate were 0.689 (p=0.002) and 0.650 (p=0.001), respectively. When the cutoff value for BUN level was considered >16 mg/dL, the sensitivity was 68%, and the specificity was 53% (OR:1.38) to predict mortality. When the cutoff value was considered >20 mg/dL, the sensitivity diminished to 40%, while the specificity increased to 90% (OR:3.9).Conclusion: In patients with CTO, BUN level is associated with increased all-cause mortality during long-term following. This relationship is independent of renal dysfunction.

The protective effects of eugenol on metabolic-syndrome, renal damages

Introduction: Metabolic syndrome consists of a group of abnormities which is involved with chronic kidney disease and nephropathy. Eugenol is an important phenolic component, which is present in many plants’ essential oils such as cloves oil with antioxidant effects. Objectives: Our study planned to demonstrate eugenol’s effects over nephrotoxicity derived from metabolic syndrome. Materials and Methods: Thirty-five male Wistar rats were picked accidentally and then divided into five groups including 1) tap water; 2) water with fructose10%; 3) water with fructose + sweet almond oil and administered intraperitoneally; 4) water with fructose+ eugenol 50 mg/kg/d and administered intraperitoneally; 5) water with fructose+ eugenol 100 mg/kg/d administered intraperitoneally. This regime lasted for 60 days, and at the beginning of day 31st, injections started for 30 days. Assessment of serum, urine and renal parameters (in homogenized kidney tissue) were conducted in the last step. Results: The results argued that the induction of metabolic syndrome following renal injury has significantly increased serum blood urea nitrogen (BUN) and creatinine (Cr) levels in the fructose group. Consumption of eugenol resulted in a significant reduction in the level of these two biochemical factors (P &lt; 0.05). The renal level of malondialdehyde (MDA) increased in the fructose group while treatment with a dose of 50 eugenol decreasing its level (P &lt; 0.05). Proteinuria and kidney tissue damage score (KTDS) increased in the fructose group compared with the tap water group (P &lt; 0.001). It is noteworthy that treatment with eugenol did not affect the level of proteinuria and KTDS with any of the used doses. Conclusion: Our results indicated the improvement of renal functioning and decrease in lipid peroxidation, although eugenol doses used in this study did not reduce proteinuria and KTDS.

Effects of prepubertal exposure to forchlorfenuron through prenatal and postnatal gavage administration in developing Sprague-Dawley rats

Forchlorfenuron (CPPU), a plant growth regulator, is widely used in agriculture. However, its long-term exposure effects on humans, especially neonates, remain unclear. Therefore, we investigated the developmental toxicity of prenatal and postnatal gavage administration of CPPU in rats. Pregnant Sprague-Dawley rats were administered 300 mg/kg/day CPPU by gavage from day 6 of gestation to the cessation of nursing. During weaning, rat offspring were administered 0, 30, 100, or 300 mg/kg/day CPPU for 4 weeks, followed by a 4-week CPPU-free recovery period. There were no significant differences in clinical symptoms, body weight, development indicators, serum biochemical parameters, sex hormone levels, sperm motility, relative organ weights, and histopathological changes among the 0–100 mg/kg/day CPPU groups. In the 300 mg/kg/day CPPU group, female rats exhibited decreased body weight, earlier time of vaginal opening (VO) and first estrus time (FE), elevated estradiol and blood urea nitrogen (BUN) levels, and upregulation of estrogen receptor 1 gene expression, whereas male rats only exhibited increases in serum BUN, creatinine, and glucose levels. Most changes were reversed after the recovery period. Furthermore, the endometrial epithelial height was significantly increased in female rats despite the absence of significant changes in uterine wall thickness and endometrial glands. Thus, CPPU may promote estradiol secretion, resulting in altered VO and FE and adverse effects in prepubertal female rats. These findings may be applied for risk assessment following CPPU exposure in humans.

Isovitexin protects against cisplatin-induced kidney injury in mice through inhibiting inflammatory and oxidative responses

In this study, we investigated the renoprotective effects and mechanism of isovitexin, a glycosylflavonoid isolated from rice hulls of Oryza sativa, against cisplatin-induced kidney injury in mice. The mice were treated with cisplatin for four consecutive days and at the second day, the mice were received with isovitexin for three consecutive days. The levels of blood urea nitrogen (BUN) and creatinine in serum and the levels of MDA, ROS, TNF-α, IL-1ß and IL-6 in kidney tissues were measured. The proteins of Nrf2 and NF-κB signaling pathways were measured by western blot analysis. Our results demonstrated that isovitexin inhibited CP-induced increases in serum BUN and creatinine. Isovitexin inhibited CP-induced inflammation by inhibiting TNF-α, IL-1ß and IL-6 production in kidney tissues. Also, isovitexin inhibited CP-induced oxidative stress by inhibiting MDA and ROS production. Furthermore, isovitexin was found to inhibit CP-induced NF-κB activation and increase Nrf2 and HO-1 expression. In conclusion, our results indicated that isovitexin protected against CP-induced kidney injury by suppressing inflammatory and oxidative responses.

Angiotensin-Converting Enzyme Inhibitor Captopril: Does it Improve Renal Function in Lipopolysaccharide-induced Inflammation Model in Rats.

Renin-angiotensin system as an important regulator of renal function has also a major role in inflammation. In the present study, the effects of captopril on renal dysfunction, renal cytokine levels, and renal tissue oxidative damage were investigated in lipopolysaccharide (LPS)-induced inflammation model in rats. Treatment of five groups of the rats was carried out as follows: (1) saline as a control, (2) LPS 1 mg/kg, and (3-5) 10, 50, or 100 mg/kg captopril 30 min, respectively, before LPS. The treatments were given for 12 days. Finally, the animals were deeply anesthetized, the blood samples were obtained, and the renal tissues were removed and kept for biochemical measurements. Administration of LPS increased serum blood urea nitrogen and creatinine (P < 0.001). Pretreatment with all doses of captopril decreased these parameters (P < 0.001). LPS also increased interleukin-6 (IL-6), malondialdehyde, and nitric oxide metabolites in the renal tissues (P<0.05 - P < 0.001), which was prevented by captopril (P < 0.05 - P < 0.001). The total thiol concentration and superoxide dismutase and catalase activities in the kidney of the LPS group were lower than the control (P < 0.001), while they were enhanced when the animals were cotreated by captopril (P <0.01 - P < 0.001). The results of the present study showed that captopril improved renal function and attenuated tissue oxidative stress in LPS-induced inflammation model in rats.

Cardioprotective effect of melatonin and agomelatine on doxorubicin-induced cardiotoxicity in a rat model: an electrocardiographic, scintigraphic and biochemical study.

The present study aimed to determine the protective effect of melatonin and agomelatine on DOX-induced cardiotoxicity in rats by electrocardiographic, scintigraphic and biochemical methods. Forty-nine male Wistar rats were randomly separated into seven groups; control (CON), doxorubicin (DOX), melatonin (MEL), agomelatine (AGO), melatonin+doxorubicin (MEL+DOX), agomelatine+doxorubicin (AGO+DOX) and melatonin+ agomelatine+ doxorubicin (MEL+AGO+DOX) groups. Cardiotoxicity was induced by intraperitoneal (i.p.) injection of DOX (18 mg/kg daily for three days). Rats receiving MEL and AGO treatment in the DOX-induced cardiotoxicity group received MEL and AGO (40 mg/kg/day, i.p., for seven days). They were injected with doxorubicin (18 mg/kg, i.p.) on days 5, 6, and 7. The rats were given MEL and AGO as substance control (40 mg/kg/day, i.p., for 7 days). On day 8 of the experiment, animals were evaluated by means of electrocardiography (ECG) and 99mtechnetium pyrophosphate (99mTc PYP) scintigraphy and their biochemical parameters [blood urea nitrogen (BUN), creatine kinase (CK), cardiac troponin T (cTnT)] were examined. DOX-induced acute cardiotoxicity in rats is characterized by conduction abnormalities in the ECG pattern (including decreased P wave and QRS complex duration, increased QT and RR intervals, and ST-segment elevation), increased serum BUN, CK, and cTnT parameters and increased 99mTc PYP uptake (p < 0.001). Pretreatment with MEL, AGO, or MEL+AGO effectively alleviated DOX-induced ECG abnormalities close to normal (p < 0.001). Moreover, serum biochemical evidence and 99mTc PYP uptake values demonstrated that pretreatment with MEL, AGO, or MEL+AGO has the same protective effect against the abnormalities produced in the heart by DOX (p < 0.001). MEL and AGO have a potential protective effect on DOX-induced cardiotoxicity. At the same time, this study suggests that 99mTc PYP is a non-invasive method suitable for early determination of DOX-induced cardiotoxicity (Tab. 3, Fig. 5, Ref. 41).

Effects of Prenatal Growth Status on Subsequent Childhood Renal Function Related to High Blood Pressure.

BackgroundHypertension is one of the major causes of chronic diseases. The effect on high blood pressure (BP) with fetal growth restriction is now well-established. Recent studies suggest that a reduced number of nephrons programmed during the intrauterine period contribute to a subsequently elevated BP, due to a permanent nephron deficit. However, few studies have examined this in children. We investigated the effects of low birth weight (LBW) and preterm birth on the renal function markers related to a high BP in childhood.MethodsWe used data from 304 children aged 7–12 years who participated in the 2014 Ewha Birth and Growth Cohort survey in Korea. We assessed the serum uric acid, cystatin C, blood urea nitrogen (BUN), creatinine levels, and the estimated glomerular filtration rate (eGFR) in childhood. Anthropometric characteristics, BP in childhood, birth weight and gestational age were collected.ResultsThe serum uric acid was significantly higher in LBW children (4.0 mg/dL) than in normal birth weight children (3.7 mg/dL). The cystatin C levels were highest among children who were very preterm (0.89 mg/dL) compared with those who were not (preterm, 0.84 mg/dL; normal, 0.81 mg/dL), although the result was only borderline significant (P for trend = 0.06). Decreased birth weight was found to be significantly associated with an increased serum BUN level in childhood. In the analysis of the effects of renal function on BP, subjects with an eGFR lower than the median value had a significantly higher diastolic BP in childhood (difference = 2.4 mmHg; P < 0.05).ConclusionThese findings suggest that LBW and preterm birth are risk factors for increased serum levels of renal function markers in childhood. Reduced eGFR levels were significantly associated with elevated diastolic BP in childhood. It is necessary to identify vulnerable individuals during their life and intervene appropriately to reduce the risk of an increased BP in the future.

Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats.

The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.

Increased Renal 2-Arachidonoylglycerol Level Is Associated with Improved Renal Function in a Mouse Model of Acute Kidney Injury

Background: Acute kidney injury (AKI) is associated with a significantly increased risk of morbidity and mortality. Ischemia–reperfusion injury (IRI) is a major cause of AKI. In this study, we investigated the role of the endocannabinoid (EC) system in renal IRI using a well-established mouse model.Materials and Methods: Renal ischemia was induced in male C57BL/6 mice by clamping both kidney pedicles for 30 min followed by 24 h of reperfusion. To increase renal 2-arachidonoylglycerol (2-AG) levels, mice were pretreated with JZL184 (16 mg/kg), 30 min before IRI. Serum creatinine and blood urea nitrogen (BUN), renal tubular damage, renal content of ECs and renal expression of markers of inflammation and oxidative stress were measured.Results: Renal IRI was associated with significantly increased serum BUN and creatinine, increased tubular damage score, increased expression of renal markers of inflammation and oxidative stress and elevated renal 2-AG content. Pretreatment with JZL184 was associated with a significant increase in renal 2-AG content and there was also improved serum BUN, creatinine and tubular damage score. However, renal expression of inflammation and oxidative stress markers remained unchanged.Conclusions: This is the first report documenting that renal IRI is associated with an increase in kidney 2-AG content. Further enhancement of 2-AG levels using JZL184 improved indices of renal function and histology, but did not lower renal expression of markers of inflammation and oxidative stress. Further studies are needed to determine the mechanisms responsible for the effects observed and the potential value of 2-AG as a therapeutic target in renal IRI.