Blood Urea Nitrogen Determinations Research Articles

Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis.

Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms. In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins. PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system. PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.

600-P: Higher Hydration Status Is Indicative of Better Glucose Tolerance

Introduction: Water intake is an important dietary behavior to replace high-caloric beverages and to enhance metabolic health. Type 2 diabetes is a metabolic disorder that has been shown to be more prevalent in Hispanics, a population shown to consume relatively less water compared to non-Hispanic Whites. The underlying cause of type 2 diabetes is insulin resistance, characterized by hyperglycemia and impaired glycemic control. However, whether a relationship exists between dehydration and the development of diabetes remains to be elucidated. Purpose: To evaluate if hydration status indicates glucose tolerance among a dominant Mexican American population. Methods: Sixty-one participants without diabetes (Age: 26.5 ± 9.1 years; BMI: 27.5 ± 6.0 kg/m2) participated in the study. Fasting blood glucose level was determined, and a 2-hour glucose tolerance test was performed following the ingestion of a 75g glucose drink. Blood glucose concentration levels were determined at 15−, 30−, 60−, 90−, and 120-minute time intervals post ingestion and glucose area under the curve was analyzed as well. Blood works were performed to determine blood urea nitrogen (BUN) and creatinine concentrations. Hydration status was estimated using the ratio of BUN to creatinine values. Results: Hydration status measured by BUN/Creatinine was positively associated with glucose intolerance measured at 15−, 30−, 60−, and 90-minute post glucose load and by glucose area under the curve (r=0.33; r=0.43; r=0.37; r=0.27; and r=0.41 respectively; p<0.05). Conclusion: Adequate fluid consumption should be encouraged for glycemic control, especially among people with high diabetes risks. Disclosure J.Apaflo: None. J.Labadah: None. G.Narvaez: None. V.M.Rocha: None. A.Mossayebi: None. S.Bajpeyi: None.

Eriocalyxin B relieves kidney damage in a rat model of membranous nephropathy by inhibiting JAK/STAT3 pathway

Purpose: To investigate the function of eriocalyxin B (EriB) in membranous nephropathy (MN) in a rat model and the related mechanisms.
 Methods: Cationic C-BSA was injected into Sprague-Dawley (SD) rats to generate a rat model of MN. The MN rats were treated with different concentrations of EriB (2.5, 5, and 10 mg/kg). After treatment, their kidneys were excised, sectioned, and hematoxylin and eosin (H&E) stained to determine renal injury, while Masson's trichrome staining was performed to determine renal tissue fibrosis. Bradford assay was used to determine rat proteinuria and ELISA employed to determine blood urea nitrogen (BUN) and serum creatinine (SCr) levels. ELISA was also used to measure IL-1β, IL-6, and TGF-α levels, while immunoblot analysis was used to assess protein expressions of related indicators in JAK/STAT3 pathway.
 Results: Compared with sham rats, MN rats showed increased the contents of proteinuria, BUN, and SCr (p < 0.01), induced serious renal injury, and increased expression of collagen I and III (p < 0.01), and fibrosis. It also elevated the levels of IL-1β, IL-6, and TGF-α (p < 0.01), causing inflammation and activation of the JAK/STAT3 pathway. EriB treatment alleviated renal injury, fibrosis, and inflammation in MN rats. With increase in EriB concentration, renal injury in MN rats was gradually alleviated.
 Conclusion: EriB alleviates renal injury in MN rats by inhibiting JAK/STAT3 pathway. Thus, EriB is a potential drug for the management of MN.

Diosmin prophylaxis reduces gentamicin-induced kidney damage in rats.

Gentamicin is an essential aminoglycoside antibiotic, but it is only used to treat severe bacterial infections due to its high nephrotoxicity in patients. We evaluated the preventive effects of diosmin (as a natural ingredient) on gentamicin-related kidney damage in rats. In this research, 28 male Wistar rats were divided into four groups: control, gentamicin (100mg/kg (i.p.), daily for 1week), gentamicin plus diosmin (50mg/kg, p.o., daily for 2weeks), and diosmin (50mg/kg/day, p.o. for 2weeks). After the final gavage, blood samples were collected for the determination of blood urea nitrogen (BUN) and creatinine. Kidneys are used for biochemical, inflammatory, and histological tests. The concentrations of creatinine, BUN, nitric oxide, malondialdehyde, tumor necrosis factor α (TNF-α), and interleukin 1 beta (IL-1β) were significantly increased. But, the level of glutathione and activities of catalase, glutathione peroxidase, and superoxide dismutase decreased during treatment with gentamicin. On the other hand, the concentrations of creatinine, BUN, nitric oxide, malondialdehyde, TNF-α, and IL-1β were significantly reduced, and the glutathione level, activities of catalase, and glutathione peroxidase were significantly increased via co-administration with diosmin. Diosmin had ameliorative impacts against gentamicin-related kidney injury due to its antioxidant and anti-inflammatory activities.

Ellagic acid and cilostazol ameliorate amikacin-induced nephrotoxicity in rats by downregulating oxidative stress, inflammation, and apoptosis.

Amikacin (AK) has the largest spectrum of aminoglycosides. However, its use is constrained because of nephrotoxicity and ototoxicity. Ellagic acid (EA) is a polyphenol present in plants. It has antioxidant, anticarcinogenic, and antimutagenic characteristics. Cilostazol (CTZ) is a phosphodiesterase Ш inhibitor, it is a potent vasodilator and antiplatelet drug. CTZ has an inhibitory effect on reactive oxygen species and superoxide generation in addition to hydroxyl radicals scavenging action. This study determines whether EA and cilostazol have a protective effect against AK-induced nephrotoxicity. Forty-nine rats were divided into seven equal groups: control normal; AK 400 mg/kg; EA 10 mg/kg; CTZ 10 mg/kg; AK 400 mg/kg plus EA 10 mg/kg; AK 400 mg/kg plus CTZ 10 mg/kg; AK 400 mg/kg plus EA 10 mg/kg and CTZ 10 mg/kg. For seven days, drugs were administered using gavage one hour before intramuscular injection of AK. Twenty-four hours after the last AK dosage, blood samples were collected to determine blood urea nitrogen and creatinine levels. Kidneys were removed for histopathological examination and measurement of: malondialdehyde (MDA), catalase (CAT), decreased glutathione (GSH), superoxide dismutase (SOD), interleukin 6 (IL6), tumor necrosis factor-alpha (TNFα), nuclear factor kappa B (NFκB), and Bcl-2 associated x protein (BAX). AK caused kidney damage, inflammatory mediator elevation, and oxidative stress and apoptotic markers. Rats receiving EA or CTZ indicated significant improvement in kidney function, decrease in oxidative stress and inflammation through NF-kB down-regulation and BAX expression. The combination of EA and CTZ showed a synergistic effect. In conclusion, EA and CTZ might play a beneficial role in preventing nephrotoxicity induced by AK partially by inhibition of tissue inflammation and apoptosis.

Impact of Pycnogenol on Acetaminophen-Induced Hepatorenal Damage

We investigated the protective effects of pycnogenol (PYC), a natural anti-oxidant with an anti-inflammatory effect, on the acetaminophen (APAP)-induced hepatorenal injury in rats. Wistar albino rats were divided into four experimental groups: control, PYC (10 mg/kg, ip), APAP (1000 mg/kg), and APAP+PYC groups. Rats were decapitated 24 hours after the APAP injection, and their blood was taken to determine blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and pro-inflammatory cytokines; TNF-α and IL-1 β. Liver and kidney tissue samples were obtained for the histological examination and the determination of malondialdehyde (MDA) and glutathione (GSH) levels as well as myeloperoxidase (MPO) and Na+/K+-ATPase activities. PYC treatment decreased the APAP-induced elevations in serum pro-inflammatory cytokines and reduced the impairment of liver and kidney functions. Furthermore, the increase in tissue lipid peroxidation and myeloperoxidase activity and the decrease in the GSH levels and Na+/K+-ATPase activity by the APAP overdose were reversed by the PYC treatment. Besides, histologic findings reinforce the protective effect of PYC in APAP-induced hepatorenal damage. PYC, which appears to have restored the GSH and depressed neutrophil infiltration and the associated release of pro-inflammatory cytokines, merits consideration as an anti-oxidant and anti-inflammatory agent in preventing APAP-induced hepatorenal damage.

Beneficial Effects of L-carnitine on Cholesterol-Induced Atherosclerosis in Rabbits: An Animal Model Study

Twenty five rabbits were randomized into five groups (n = 5): Normal Control group(NC) were kept on a plain chow diet for 75 days. AT group were kept on a hypercholesterolaemicdiet for 75 days. ATO (atorvastatin) group were fed the same diet and receivedatorvastatin orally (20mg/kg/day) from day 45 for 30 days. L group were fed thesame diet and intraperitoneal L-carnitine (250 mg/kg/day) from day 45 for 30 days (completionof treatment). ATO/L group were fed the same diet and atorvastatin orally(l0 mg/kg/day) and L-carnitine intraperitoneally (125 mg/kg/day) from day 45 for 30 days.Histopathological investigations of aorta and assessment of serum profile were carried out to determine Blood urea nitrogen (BUN), creatinine (Cr), Sodium (Na), potassium (K), Phosphorus (P), triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Alkaline phosphatase(ALK). The aorta wall of hypercholesterolaemic rabbits showedfoam cells with disrupted endothelial lining and changed muscle fibers. The animals of ATO and ATO/L groups had normal aorta wall. TG significantly increased in hypercholesterolaemic rabbits.L-carnitine treatment significantly reduced TG (P 0.05) except for L group, where BUN level wassignificantly higherthan those in ATO and ATO/L groups (P<0.05). Serum AST, ALT and ALK levels were significantly reduced in L-carnitine treated animals compared to ATO group (P<0.05). L-carnitine prevented progression of atherosclerotic lesions.

Development of a Sensitive High-Resolution Mass Spectrometry Approach for Urea Nitrogen Quantitation in Small Volumes of Bronchoalveolar Lavage Fluid (BALF).

A sensitive, selective, and quantitative method incorporating high-resolution mass spectrometry was developed for the determination of blood urea nitrogen (BUN) in bronchoalveolar lavage fluid. The method requires no sample cleanup or derivatization prior to analysis. High-performance liquid chromatography (HPLC) on a Hypersil Gold PFP column (100 × 3 mm, 3 μm particle size) connected to a C18 guard column was employed for a 10 min chromatographic separation. The detection of urea was achieved using a Thermo Scientific Q-Exactive Plus instrument incorporating selected ion monitoring (SIM) modes for the protonated adduct of urea. The urea analytical measuring range for the method is 0.047-17.134 mg/dL, resulting in a BUN analytical measurement range of 0.022-8.007 mg/dL, which allows for quantitation over 3 orders of magnitude (R2 = 0.999). In addition, the method is suitable for small sample volumes (15 μL) with a high level of accuracy, precision, and specificity.

Exposure of cigarette smoke aggravates noise induced kidney damage

Introduction: Noise is defined as an interfering and unwanted sound. Exposure to noise induces health problems in humans and animals. Cigarette smoke (CS) has also been known to cause serious problems in health hazard and leads to many kinds of diseases. However, the effects of these agents on the kidney are poorly studied. Objectives: The current study purposes to investigate the impact of noise and/or CS on rat’s kidney Materials and Methods: Four groups of six Wistar adult male rats were used. They randomly were divided into four groups of rats. The first group was used as control. The second group was exposed to noise. The third group was exposed to cigarette smoking and the fourth group was exposed to both noise and CS. The experiments were repeated for two weeks (five days per week). Twenty-four hours after last exposure, the animals were killed by sodium pentobarbital overdose. Renal function was evaluated by the determination of blood urea nitrogen (BUN) and creatinine levels. Oxidative stress was estimated by glutathione (GSH) and malondialdehyde (MDA) assays. Results: The concentrations of BUN and creatinine remarkably raised (P ≤ 0.05) in all groups compared to those in control rats. However, elevations of the biochemical tests were more predominant in rats exposed to combined noise and CS. Elevation of MDA was observed in all exposed rats, while it was more pronounced in the animals exposed to the combined noise and CS when compared to control, CS or noise exposure rats alone. The level of GSH decreased in all exposed groups. It was more obvious in rats exposed to the combined noise and CS when compared to those of control and exposure rats to noise or CS separately. Conclusion: Exposure to noise or CS impaired renal function. Generation of oxidative stress at least in part may be responsible for their nephrotoxicity. Our findings demonstrated CS aggravated noise induced impairment of renal function.

Pretreatment with berberine protects against cisplatin-induced renal injury in male Wistar rats.

Berberine (BBR), an isoquinoline alkaloid, has been reported to be an antioxidant agent. This study was conducted to investigate the effect of BBR against nephrotoxicity induced by cisplatin (Cis) in male rats. In this experimental study, 28 Wistar male rats were randomly divided into four groups. Rats were pretreated with BBR (100mg/kg/day, p.o.) for 7 consecutive days and Cis (7.5mg/kg, i.p.) was administrated on the 7th day, 1h after the last dose of BBR. Blood samples were collected to determine blood urea nitrogen (BUN) and creatinine (Cr) levels. Malondialdehyde (MDA), glutathione (GSH), protein carbonyl (PC), and nitric oxide (NO) levels and the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and myeloperoxidase (MPO) were assessed in the left renal tissue. Also, the mRNA expression of SOD2 and PGx1 was measured in the left renal tissue. The right kidney was used for histopathological evaluation. Our results revealed that the levels of Cr, BUN, MDA, NO, and PC and the MPO activity increased by Cis administration. Also, we found that Cis decreased renal GSH level and SOD, GPx, and CAT activities. Pretreatment with BBR for 7 consecutive days significantly attenuated the Cis-induced nephrotoxicity via increasing the antioxidant capacity and reducing the oxidative stress indices in the renal tissue. Moreover, the renoprotective effect of BBR was confirmed by the histopathological evaluation of the kidneys. Our results indicated that BBR has produced amelioration in biochemical indices and oxidative stress parameters against Cis-induced nephrotoxicity.

Effect of oral urea supplementation on the endometrial transcriptome of mares

An intravenous large dose of protein led to an increased blood urea nitrogen (BUN), resulting in a lesser uterine pH and altered uterine gene expression in mares. The objective of the present study was to evaluate effects of a more physiological methodology to increase BUN on the endometrium of mares. Mares were fed hay and a treatment or control diet (n = 11 mares/treatment) in a crossover design starting at time of ovulation detection (D0) and continuing until D7. Mares of the treated group were fed urea (0.4 g/kg BW) with sweet feed and molasses, and those of the control group were fed sweet feed and molasses. Blood samples were collected daily, 1 hour after feeding, for BUN determination. Uterine and vaginal pH were determined after the last feeding on D7, and endometrial biopsies were performed. The RNA sequencing of the endometrium of a subset of mares (n = 6/treatment) was conducted. Differentially expressed genes (DEGs) between treatments were calculated (FDR-adjusted P-value<0.1). Urea-treated mares had greater BUN (P < 0.05), with no differences in uterine and vaginal pH compared to control mares. A total of 60 DEGs were characterized, those with largest fold change were SIK1, ATF3, SPINK7, NR4A1 and EGR3. Processes related to necrosis and cellular movement were predicted with the DEGs. Dietary administration of urea resulted in transcriptomic changes in the endometrium of mares related to necrosis, tissue remodeling and concentration of lipids. The observed changes in gene expression after an increased BUN might result in a disruption to the endometrium.

Evaluation of Oxidative Stress Biomarkers in the Renal Tissue of Rats and Serum Biochemical Parameters After the Administration of Nitrate in Drinking Water and Vitamin C: an Experimental Study

Background: Nitrate (NO3-) is one of the inorganic anions produced from the oxidation of nitrogen. The organic or inorganic nitrogen may act as a carcinogen depending on the reduction of nitrate to nitrite and the subsequent reactions of nitrite with other molecules, leading to the formation of N-nitroso compounds. Objectives: This study aimed to determine the effects of nitrate and Vitamin C on oxidative stress in the renal tissue of rats. Methods: This experimental study was conducted in Iran during the 2017 - 2018. The sample size was estimated to include 55 Wistar male rats using Morgan's table and Cochran's formula. In total, 49 rats were selected and divided into seven groups of: (1) NO3 = 0 mg/L (control), (2) NO3 = 10 mg/L, (3) NO3 = 45 mg/L, (4) NO3 = 200 mg/L, (5) NO3 = 10 mg/L + Vitamin C 20 mg/100 g BW (Body Weight), (6) NO3 = 45 mg/L + Vitamin C 20 mg/100 g BW, and (7) NO3 = 200 mg/L + Vitamin C 20 mg/100 g BW. Blood samples were obtained to determine blood urea nitrogen (BUN) and creatinine. An autopsy was performed on the renal tissue to evaluate oxidative stress indicators including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Results: In this research, the fourth group showed a significant increase in the level of creatinine (50.14 ± 2.6, 43.14 ± 1.21, P = 0.01) and BUN (0.72 ± 0.04, 0.57 ± 0.11, P = 0.003) compared to the control group. On the other hand, a significant increase was observed in the level of MDA in the fourth group compared to the control group (P = 0.01), whereas a significant reduction was found in the levels of CAT (P = 0.001), SOD (P = 0.02), and GSH (P = 0.02). In addition, the levels of creatinine and BUN significantly reduced in the seventh group compared to the fourth group (P < 0.05). Furthermore, the use of Vitamin C resulted in a significant reduction in MDA and an increase in SOD, CAT, and GSH in the seventh group compared to the fourth group (P < 0.05). Conclusions: According to the results of the study, nitrate in drinking water and the prescription of Vitamin C had no significant effect in the presence of nitrate doses of 10 and 45 mg/L. However, a 200 mg/L dose of nitrate significantly affected BUN, serum creatinine, and oxidative stress indicators, causing the kidney disease.

Study the Effect of Apocynin on Some Renal Functions in Ischemia / Reperfusion Injury in Male Albino Rats

Background: Apocynin (4-hydroxy-3-methoxyacetophenone) which isolated from the traditional medicinal plant Picrorhiza kurroa, is a naturally occurring methoxy-substituted catechol, experimentally used as an inhibitor of NADPH oxidase and of the concomitant ROS production. Apocynin also proved to be a potent anti-inflammatory agent, based on the selective inhibition of the production of ROS by activated human PMNs. Aim of the Study: to explore the protective effect of Apocynin and the NADPH oxidase inhibitor on kidney damage induced by ischemia/reperfusion (I/R) in a rat model. Subjects and Methods: Fourty male albino rats were categorized into four equal groups of 10. Group 1: Sham operated control group, Group 2: Ischemia / reperfusion (I/R) group; which underwent bilateral renal ischemia for 1 hour followed by a 23 hour reperfusion, Group 3: 4-week Apocynin treated group in which rats received Apocynin with a dose o16 mg/kg /day for 4 weeks followed by bilateral renal ischemia for 1 hour then 23 hour reperfusion afterwards , and Group 4: 8-week Apocynin treated group in which rats received Apocynin with a dose of 16 mg/kg /day for 8 weeks then bilateral renal ischemia for 1 hour followed by 23 hour reperfusion. After reperfusion, the animals were sacrificed, the blood samples were collected for determination of blood urea nitrogen, serum creatinine, 24 hour urine were collected for determination of creatinine clearance. Kidneys of all animals were harvested and evaluated biochemically through determination of tissue MDA, MPO, GPX and catalase level. Results: Kidney tissue MDA, MPO, serum BUN and Creatinine levels were found to be significantly higher in the I/R group. GPx level showed a significant decrease, while there was a slight decrease in Catalase level when compared with Sham operated group. Creatinine clearance was impaired in renal I/R group. Renal I/R injury has also induced an extensive tubular necrosis, glomerular damage, and apoptosis. Apocynin significantly reduced MDA and MPO and increased GPX and catalase in both treatment groups when compared to the I/R group (p< 0.001). The elevated BUN and creatinine levels were significantly reduced in treatment groups, also creatinine clearance was restored to around normal value. Conclusion: with accordance to the findings and outcome of the present study, Apocynin has exerted protective effects against ischemia/reperfusion injury by ameliorating the kidney damage induced by I/R injury to a significant extent. However, there was no significant difference in the outcome if the treatment was extended from 4 to 8 weeks.

Effects of Platelet-Rich Plasma on Kidney Regeneration in Gentamicin-Induced Nephrotoxicity.

Platelet-rich plasma (PRP) as a source of growth factors may induce tissue repairing and improve fibrosis. This study aimed to assess the effects of PRP on kidney regeneration and fibrosis in gentamicin (GM)-induced nephrotoxicity rat model by stereological study. Thirty-two male rats were selected. Nephrotoxicity was induced in animals by administration of GM (80 mg/kg/daily, intraperitoneally [IP], 8 day) and animals were treated by PRP (100 µL, intra-cortical injection using surgical microscopy, single dose). Blood samples were collected for determine blood urea nitrogen (BUN) and creatinine (Cr) before and after PRP therapy. At the end of experiment, right kidneys were sectioned by Isotropic Uniform Random (IUR) method and stained with H & E and Masson’s Trichrome. The stereological methods were used for estimating the changes in different structures of kidney. PRP increased the number of epithelial cells in convoluted tubules, and decreased the volume of connective tissue, renal corpuscles and glomeruli in GM-treated animals (P < 0.05). Our findings indicate that PRP had beneficial effects on proliferation of epithelial cells in convoluted tubules and ameliorated GM-induced fibrosis.

ALLEVIATION OF CISPLATIN INDUCED NEPHROTOXICITY IN ALBINO RATS BY ROOTS OF Catunaregam uliginosa

ABSTRACT:Objective: To evaluate the nephroprotective effect of ethanolic extract of roots of Catunaregam ulginosa in cisplatin induced nephrotoxicity in albino rats.Methodology: Ethanolic extract was prepared by hot extraction method and subjected to preliminary phytochemical studies. Based on acute toxicity studies nephroprotector was screened at two dose levels i.e., 200mg/kg bd wt and 400 mg/kg bd wt in both curative and prophylactic regimens. Cisplatin at a dose of 5mg/kg bd. wt was given intraperitoneally to induce nephrotoxicity. Nephroprotector activity was assessed by determining blood urea nitrogen (BUN), serum creatinine(SC), urinary total protein(UTP) and creatinine clearance. Antioxidant enzymes like super oxide dismutase (SOD), catalase (CAT), glutatathione reduced (GSH) activities and lipid peroxidation (LPO) levels were determined in renal tissue. Histological studies had been carried per se.Results: Animals which received cisplatin exhibited significant increase in serum marker levels, increased urinary total protein excretion and reduced creatinine clearance. Further significant decrease in GSH, SOD, CAT and increase in LPO levels was observed. Ethanolic extract of roots of Catunaregam ulginosa reversed the effects induced by cisplatin in dose dependent manner in both curative and prophylactic regimens. Histological studies substantianed the above results.Conclusion: The findings of the present study support the alleviation of cisplatin induced nephrotoxicity by the ethanolic extract of roots of Catunaregam ulginosa and thus validate its ethnomedicinal use.Key words: Catunaregam ulginosa, Cisplatin, Nephrotoxicity, Lipid peroxidation

Effect of heme oxygenase-1 transduced by cell penetrating peptide PEP-1 on renal injury in rats with acute paraquat poisoning

Objective: To study the effects of heme oxygenase-1 transduced by cell penetrating peptide PEP-1 on renal injury in acute paraquat-induced rats. Methods: The fusion protein PEP-1/HO-1 was manufactured by genetic engineering methods. One hundred and twenty-six healthy adult Sprague-Dawley (SD) rats (63 male, 63 female) were randomly divided into three groups: (1) Control group: 42 rats, (2) Poisoned group: 42 rats, (3) PEP-1/HO-1 intervention group: 42 rats. The rats in Poisoned group and intervention group were treated intraperitoneally with paraquat (25 mg/kg) deliquated with normal saline. Control group rats were treated with the same way of normal saline as the others. Intervention group rats were injected 1 mg of the fusion protein PEP-1/HO-1 into the left iliac vein at 30 minutes before the administration of the paraquat. After abdominal dissection with ether anaesthesia, six rats respectively from each of three groups were taken tissue samples from kidney at 1 st、6 th、12 th、24 th、36 th、48 th、and 72 nd hour respectively. Tissue Superoxide Dismutase (SOD) activity and Malondialdehyde (MDA) content were measured, and renal tissue was quickly remained to observe the expression of Heme Oxygenase-1 (HO-1) by the method of immunohistochemistry. Blood samples were collected from the abdominal aorta for determination of Blood Urea Nitrogen (BUN) and Creatinine (Cr) concentrations in plasma. Results: To prepare high purity fusion protein PEP-1/HO-1 Successfully. The levels of the plasma Bun and Cr in Poisoned and intervention group were significantly higher than that in Control group in the six to seventy-two hours (P<0.01) ; Whereas the increases of Bun and Cr were markedly intibited in PEP-1/HO-1 intervention group, in which, the levels of Bun and Cr in the six to seventy-two hours were significantly lower than Poisoned group (P<0.05). Compared with control group, the levels of MDA in poisoned groups were increased in the one to forty-eight hours and the levels of it in groups PEP-1/HO-1 in the one to thirty-six (P<0.01 or P<0.05). The T-SOD activity of the poisoned group was decreased in the one to thirty-six hours than that of the control group (P<0.05). Compared with poisoned group, the T-SOD activity at various points in time was increased in group PEP-1/HO-1 (P<0.01). In control group, there was only very weak expressions of HO-1 in the normal renal tissue. In poisoned and intervention group, the expressions of HO-1 were significantly higher than that in control group in all time (P<0.01). The HO-1 expressions of PEP-1/HO-1 group in all time was significantly higher than that in poisoned group (P<0.01 or P<0.05). Conclusion: The HO-1 protein Can be successfully transduced into renal tissue by cell penetrating peptide PEP-1 and the transduced HO-1 protein reduces renal injury of the acute paraquat-induced rats by inhibiting lipid peroxidation response.

Protective effect of the methanolic leaf extract of Eclipta alba (L.) Hassk. (Asteraceae) against gentamicin-induced nephrotoxicity in Sprague Dawley rats

Ethnopharmacological relevanceEclipta alba, also known as Eclipta prostrata, is a weed of the family Asteraceae found in tropical and subtropical regions widely used in herbal medicine, including treatment of renal diseases. Aim of the studyThis study aims to evaluate the protective effect of the methanolic leaf extract of Eclipta alba on gentamicin-induced nephrotoxicity in rats. Materials and methodsNephrotoxicity was induced in rats by subcutaneous injection of gentamicin (80mg/kg/day for seven days). Quercetin was used as a positive control. The nephroprotective activity was evaluated by determining blood urea nitrogen, serum creatinine, urinary microprotein, renal catalase and malondialdehyde levels. ResultsThe extract protected the rat kidneys against gentamicin-induced renal tubular alterations and rises in blood urea nitrogen, serum creatinine, and microprotein levels. Lipid peroxidation and decrement in catalase levels were also ameliorated. ConclusionThe study revealed the protective effect of the methanolic leaf extract of E. alba and suggests that the probable mechanism for the nephroprotection by the extract may be due to its good radical scavenging activity and Fe3+ ion-reducing ability.

Association of blood neutrophil lymphocyte ratio in the patients with postmenopausal osteoporosis.

Objective:To investigate the relationship between blood neutrophil lymphocyte ratio (NLR) and postmenopausal osteoporosis in Chinese women without diabetes.Methods:Two hundred and thirty three postmenopausal women without diabetes were included in this study. The clinical data of patients including age, and body mass index (BMI) were recorded. Blood samples were obtained to determine Blood urea nitrogen (BUN), Uric acid (UA), Albumin (ALB), Creatinine (CREA), Total Cholesterol(TC), Triglyceride (TG), Fasting plasma glucose (FPG), Glycosylated Hemoglobin (HbAlc), 25-hydroxyitamin D (25-OHD) level. NLR was calculated using the following formulas: NLR = Neutrophil count / lymphocyte count; Bone mineral density (BMD) of the lumbar vertebrae and the femoral neck was measured. The relationship between NLR and postmenopausal osteoporosis statistical methods was analyzed.Results:Age, BMD, Albumin (ALB), Creatinine(CREA), Triglyceride (TG) and NLR level were different in the three groups (P<0.05). Logistic regression analysis showed that the age and NLR level were risk factors for postmenopausal osteoporosis.Conclusions:NLR level was strongly associated with BMD in the postmenopausal women without diabetes, suggesting that NLR could become a helpful clinical tool in the assessment of postmenopausal osteoporosis.

Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure.

Heart failure guidelines suggest evaluating renal function as a routine work-up in every patient with heart failure. Specifically, it is advised to calculate glomerular filtration rate and determine blood urea nitrogen. The reason for this is that renal impairment and worsening renal function (WRF) are common in heart failure, and strongly associate with poor outcome. Renal function, however, consists of more than glomerular filtration alone, and includes tubulointerstitial damage and albuminuria. For each of these renal entities, different biomarkers exist that have been investigated in heart failure. Hypothetically, and in parallel to data in nephrology, these markers may aid in the diagnosis of renal dysfunction, or for risk stratification, or could help in therapeutic decision-making. However, as reviewed in the present manuscript, while these markers may carry prognostic information (although not always additive to established markers of renal function), their role in predicting WRF is limited at best. More importantly, none of these markers have been evaluated as a therapeutic target nor have their serial values been used to guide therapy. The evidence is most compelling for the oldest-serum creatinine (in combination with glomerular filtration rate)-but even for this biomarker, evidence to guide therapy to improve outcome is circumstantial at best. Although many new renal biomarkers have emerged at the horizon, they have only limited usefulness in clinical practice until thoroughly and prospectively studied. For now, routine measurement of (novel) renal biomarkers can help to determine cardiovascular risk, but there is no role for these biomarkers to change therapy to improve clinical outcome in heart failure.

Assessment of urinary kidney injury molecule-1 and interleukin-18 in the early post-burn period to predict acute kidney injury for various degrees of burn injury.

BackgroundBurn patients with AKI have a higher mortality, rapid diagnosis and early treatment of AKI are necessary. Recent studies have demonstrated that urinary KIM-1 and IL-18 are potential biomarkers of early-stage AKI, however, changes in urinary KIM-1 and IL-18 levels are unclear in patients with burns. The aim of our study was to determine whether combined KIM-1 and IL-18 are more sensitive than traditional markers in detecting kidney injury in patients with burns.MethodsNinety-five burn patients hospitalized at the Burns and Plastic Surgery Center of our hospital from April 2013 to September 2013 were enrolled into this prospective study and divided into mild- (n = 37), moderate- (n = 30) and severe-burn groups (n = 28) by burn injury surface area. In the moderate- and severe-burn groups, patients were subcategorized to either the acute kidney injury (AKI) group, in which serum creatinine (Scr) increased to ≥26.5 μmol/L within 48 h, or the non-AKI group. Fifteen healthy subjects were selected as a control group. Blood specimens were collected to determine blood urea nitrogen (BUN), Scr, and other biochemical indicators. Urine samples collected at admission and 48 h after admission were analyzed for KIM-1 and IL-18. Correlations among urinary KIM-1 and IL-18, burn degree, and clinical biochemical indicators were investigated.ResultsAKI occurred in 11.2 % of burn patients (none in the mild-burn group). AKI developed 48 h after admission in 10.0 % of the moderate- and 28.6 % of the severe-burn groups. Urinary KIM-1 concentration in the moderate- and severe-burn groups was significantly higher than that in the control group; urinary IL-18 concentrations did not differ significantly among the burn and control groups. The AKI group had significantly higher concentrations of urinary KIM-1 and IL-18 than the non-AKI group, both at admission (p = 0.001 and p < 0.001, respectively) and 48 h later (p = 0.001 and p < 0.001, respectively). Both urinary KIM-1 and IL-18 increased before Scr. Receiver operating-curve (ROC) analysis demonstrated that KIM-1 combined with IL-18 predicted AKI with 72.7 % sensitivity and 92.8 % specificity. The area under the ROC curve was 0.904.ConclusionsOur results suggest that urinary KIM-1 and IL-18 may be used as early, sensitive indicators of AKI in patients with burns of varying degrees and provide clinical clues that can be used in early prevention of AKI.