Histopathological Changes In Kidney Research Articles

Quercetin and lithium chloride potentiate the protective effects of carvedilol against renal ischemia-reperfusion injury in high-fructose, high-fat diet-fed Swiss albino mice independent of renal lipid signaling

Renal ischemia-reperfusion injury (R-IRI) is the main cause of acute renal failure. Carvedilol has been shown to protect against R-IRI. However, the underlying mechanisms are still not completely clarified. This study aimed to investigate the role of lipid signaling in mediating carvedilol protective effects against R-IRI in insulin-resistant mice by using two different lipid signaling modulators, quercetin and lithium chloride (LiCl). Mice were fed high-fructose, high-fat diet (HFrHFD) for 16 weeks to induce insulin resistance. At the end of feeding period, mice were randomly distributed into five groups; Sham, R-IRI, Carvedilol (20 mg/kg, i.p.), Carvedilol + Quercetin (10 mg/kg, i.p.), Carvedilol + LiCl (200 mg/kg, i.p.). R-IRI was performed by applying 30 min of unilateral renal ischemia followed by one hour of reperfusion. Quercetin and LiCl were administered 30 min before carvedilol administration and carvedilol was administered 30 min before ischemia. Changes in kidney function tests, histopathology, fibrosis area, lipid signaling, inflammatory, apoptosis and oxidative stress markers in the kidney were measured. Results showed that R-IRI decreased kidney function, impaired renal tissue integrity, modulated lipid signaling and increased renal inflammation, apoptosis and oxidative stress. Carvedilol treatment decreased the detrimental effects induced by R-IRI. In addition, pre-injection of both quercetin and LiCl potentiated the reno-protective effects of carvedilol against R-IRI independent of changes in lipid mediators like phosphatidyl inositol 4,5 bisphosphate (PIP2) and diacylglycerol (DAG). In conclusion, quercetin and LiCl potentiate the protective effects of carvedilol against R-IRI in HFrHFD-fed mice by reducing inflammation and oxidative stress independent of lipid signaling.

Effect of camphor on biochemical factors and gene expression of antioxidant enzymes, inflammatory and apoptotic factors against gentamicin-induced nephrotoxicity in rats

Introduction: Camphor is a natural antioxidant with anti-inflammatory and tissue repair properties. Nephrotoxicity is the most important side effect of gentamicin (GEM) administration. Therefore, investigating the effect of natural antioxidants can resolve this complication. Objectives: We aimed to assay the effect of camphor on biochemical factors and gene expression of antioxidant enzymes (catalase [CAT], glutathione peroxidase [GPX]) and inflammatory markers (tumor necrosis factor-alpha [TNF-α], nuclear factor kappa-B [NF-κB], interleukine-6 [IL-6]), and apoptotic indices (BCL2-associated X protein [Bax], B-cell lymphoma 2 [Bcl-2], caspase-3)], against GEM-induced nephrotoxicity in rats. Materials and Methods: Thirty adult male Wistar rats were allocated to five groups. Positive control and treatment groups were given GEM to induce nephrotoxicity. Animal treatment groups were treated with camphor in olive oil for 12 days. Renal biopsies, serum, extraction of renal tissue and urine of rats were taken after the twelfth day. Biopsies were examined for structural changes using a light microscope, moreover, apoptosis, desired biochemical and inflammatory factors, were investigated by suitable methods. Results: Camphor had no effect on biochemical factors, including malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), urea, creatinine and urine protein. However, it reduced the gene expression of TNF-α, NF-κB, IL-6, Bax, and caspase-3 and increased the gene expression of GPX and CAT and Bcl-2. Moreover, camphor improved kidney histopathological changes in the camphor groups in comparison with the GEM group. Conclusion: Camphor can be useful in the attenuation of GEM-induced nephrotoxicity based on expression levels of examined enzymes and factors and improving kidney histopathological changes.

Combined Effects of Radiofrequency Electromagnetic Fields and X-Ray in Renal Tissue and Function.

PurposeBiochemical and histopathological properties of renal tissues were reported to be affected by both radiofrequency electromagnetic fields (RF-EMF) and ionizing radiation. The radiation-induced changes in the kidney, including the serum levels of blood urea nitrogen (BUN) and creatinine (Cr), could lead to adverse health outcomes such as chronic kidney disease. These complications signify the importance of the research in this field. Thus, in this study, the effects of ionizing and non-ionizing radiations, as well as their combination, were assessed by evaluating the alteration in BUN, Cr, and histopathological changes in kidney tissue.Materials and MethodsNinety-six male Wistar rats were randomly divided into six groups and were exposed to either 900/1800MHz (mobile phone) or 2.4 GHz RF-EMF (Wi-Fi) radiation for 14 days, 8Gy x-ray, or their combination. Sera were collected from 2 mL of rat blood, then BUN and Cr levels were determined. Also, renal samples were stained with hematoxylin and eosin and evaluated histopathologically.ResultsBoth BUN and Cr levels raised non-significantly after exposure to 8 Gy x-rays. Moreover, all measurements in the samples of x-ray groups were in borderline or higher than normal values. The BUN levels of control, Wi-Fi, x-ray, and Wi-Fi+x-ray groups were not significantly different. However, Cr levels in the Wi-Fi group were significantly higher than those of the controls, and BUN to Cr ratio levels were significantly lower than those of the controls. Also, tubular atrophy and vessel wall thickening were associated with these exposures.ConclusionExposure to 900/1800MHz, 2400 MHz EMF can alter the kidney function. However, pre-exposure to 900/1800MHz EMF could modulate the acute adverse effects of lethal x-ray dose, which addresses the adaptive response in the kidney.

Nierenpathologische Befunde bei COVID-19-Patienten

ZUSAMMENFASSUNGIm Verlauf einer Infektion mit dem SARS-CoV-2-Virus kommt es nicht selten zu einer akuten Niereninsuffizienz. Bei einem Teil der Patienten liegt bereits ein vorbestehender chronischer Schaden vor, zumeist aufgrund einer hypertensiven Schädigung, zum Teil auch aufgrund einer diabetischen Glomerulosklerose. Wie es zur akuten Komponente eines Nierenversagens kommt, ist im Einzelnen nicht geklärt, eine akute T-Zell-vermittelte interstitielle Nephritis scheint typischerweise nicht zu bestehen. Über den angiotensin converting enzyme Rezeptor 2 treten die Viren in die menschlichen Zellen ein. Die Expression dieses Rezeptors in Nierenzellen und der Nachweis von Viren in der Niere legen nahe, dass es zu einer direkten Nierenzellschädigung durch das Virus kommen kann. Zusätzlich spielt wahrscheinlich auch eine indirekte Schädigung der Tubulusepithelzellen über durch die Viren induzierte Komplementfaktoren und Zytokine sowie über eine gestörte Perfusion, z. B. über Fibrinthromben sowie eine Kongestion bei Rechtsherzinsuffizienz eine Rolle. Zusammenfassend entsteht ein akutes Nierenversagen bei COVID-19-Patienten wahrscheinlich zumeist multifaktoriell.

Saponins from Panax japonicus ameliorate age-related renal fibrosis by inhibition of inflammation mediated by NF-κB and TGF-β1/Smad signaling and suppression of oxidative stress via activation of Nrf2-ARE signaling

BackgroundThe decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. MethodsSprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. ResultsAfter SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. ConclusionThese results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

Abstract 5346: Preclinical evaluation of maximum tolerated dose (MTD) following single dose administration of 212Pb-RM2

Abstract Introduction: Lead-212 (Pb-212)-RM2 is under evaluation as a potential BB2r targeted alpha therapy (TAT) agent for the treatment of BB2r positive prostate cancers. The purpose of this study was to define maximum tolerated dose (MTD) levels for conducting initial therapeutic efficacy studies using human prostate cancer xenograft models and to identify targeted organs and tissues for assessing potential radiotoxicity effects. Methods: The RM2 peptide (DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) was commercially synthesized and radiolabeled with Pb-212 eluted from a Ra-224/Pb-212 generator. Radiosynthesis was accomplished using an Eckert &amp; Ziegler PharmTracer. HPLC QC confirming &amp;gt;93% product purity was performed prior to and post administration of Pb-212 RM2. CF1 mice were administered a single intravenous bolus of either saline (non-treated controls / NTC), 50uCi, 100uCi, or 200uCi of 212Pb-RM2. Weekly complete blood counts (CBC), body weight (BW), and body condition score (BCS) were obtained up to 30 weeks post administration. Subsets of 3-5 mice/group were harvested at 30, 50, 70, 90 days, and 30 weeks for histopathology analysis and pooled serum analysis. An additional set of mice (n=3/group/time point) were administered saline (NTC), 50uCi or 200uCi of Pb-212 RM2 and tissues/serum were obtained at 2, 5, and 7 days to evaluate ALT, AST, BUN, lipase, amylase, and creatinine levels at early timepoints. Results: We observed BW loss in all treatment groups compared to the NTC. We further observed that only the high dose (200uCi) treatment group experienced weight loss that was significantly (P=0.0168) below that of the NTC at 30 weeks. No animals were removed from the study due to BW loss. WBC counts were suppressed at Week1(100uCi and 200uCi groups) and fully recovered by Week 2. WBC counts for all treatment groups were not significantly different at 30 weeks. Platelet counts were slightly suppressed at Week1 (all groups) and fully recovered by Week 2. Week 30 platelet counts were consistent between all treatment groups. Significantly elevated amylase/lipase levels were observed (Day 2) in the 200uCi treatment group with recovery to normal by Day 5. Liver (ALT and AST) and kidney (BUN and creatinine) markers showed nominal changes between groups. Marked changes in pancreas and kidney histopathology were observed only at 30 weeks (100uCi and 200uCi group). Conclusions: Based on BW, CBC, histopathology, and serum analysis, the 50uCi and 100uCi dose levels of Pb-212 RM2 appear to be well tolerated. The high dose Pb-212 RM2 group (200uCi) presented with initially elevated pancreatic enzymes (Day 2) and altered histopathology of the pancreas and kidney appearing only at 30 weeks post treatment. These data suggest that preclinical single dose administration of Pb-212 RM2 TAT at 100uCi or lower should be tolerable. This work was supported by USVA IK6BX004856, USVA IO1BX001699, and NCI RO1CA222293. Citation Format: Tammy L. Rold, Elisabeth A. Devanny, Nkemakonam C. Okoye, Thomas P. Quinn, Timothy J. Hoffman. Preclinical evaluation of maximum tolerated dose (MTD) following single dose administration of 212Pb-RM2 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5346.

Icariin Prevents Extracellular Matrix Accumulation and Ameliorates Experimental Diabetic Kidney Disease by Inhibiting Oxidative Stress via GPER Mediated p62-Dependent Keap1 Degradation and Nrf2 Activation.

The present study aimed to determine whether icariin could attenuate type 1 diabetic nephropathy (T1DN) induced by streptozotocin (STZ) after 4 weeks or not. Therefore, its therapeutic effect on diabetic kidney disease was investigated in view of reactive oxygen (ROS) and extracellular matrix (ECM) generation in human glomerular mesangial cells under high glucose. To establish the participation and the key role of GPER and Nrf2 in ECM deposition, a combination of G15 (antagonist of GPER) or siGPER and siNrf2 were performed, respectively. The results showed that T1DN can be significantly inhibited by oral icariin, evidenced by improvement of 24 h urinary volume, 24 h proteinuria, microalbuminuria, and histopathological changes of kidney. Icariin decreased the levels of intracellular superoxide anion, impeded the generation of fibronectin and increased the expression and activity of antioxidant enzymes in the human glomerular mesangial cells treated with high glucose. It acted as a GPER activator, increased dissociation of Nrf2/Keap1 complexes, combination of Keap1/p62 complexes, Nrf2 translocation to nuclear, Nrf2/ARE DNA binding activity, and ARE luciferase reporter gene activity in glomerular mesangial cells. The Nrf2 inhibitor ML385 or siNrf2 obviously abolished extracellular matrix (ECM) generation inhibited by icariin. Furthermore, icariin-induced Nrf2 activation was mainly dependent on p62-mediated Keap1 degradation, which functions as an adaptor protein during autophagy. The GPER antagonist G15 and siGPER obviously abolished the above effects by icariin. Taken together, the present study demonstrated that the therapeutic effects of icariin on type 1 diabetic nephropathy in rats via GPER mediated p62-dependent Keap1 degradation and Nrf2 activation.

THE EFFECT OF POLYPROPYLENE PLASTIC RESIDUE ON HEATED PALM OIL AGAINST THE HISTOPATHOLOGICAL CHANGES OF KIDNEY ON MALE RATS (Rattus norvegicus)

This research was conducted to observe the effect of polypropylene plastic residue on heated palm oil against the histopathological changes on rat’s kidney. There were 18 male rats (Rattus norvegicus) that used as the examination animal and were divided into three groups and were given the mixture of heated palm oil and polypropylene plastic per oral with intubation needle. The treatment was done for five weeks. The treatment for P0 group was 84 g of palm oil, for P1 was 84 g of palm oil with 2.3 g of plastic, and for the P2 was 84 g of palm oil with 6.8 g of plastic. The histopathological changes of the kidney were observed using microscope with 400x magnification and the data was analysed using Kruskal-Wallis and continued with Mann Whitney U test. The result showed that there were significant differences between three groups of treatment (P&lt;0.05). There were effects of polypropylene plastic residue on heated palm oil against the histopathological changes of kidney in this research such as cast, epithelial sloughing and necrosis in the mild scale.

HISTOPATHOLOGICAL CHANGES OF KIDNEY OF BROILER CHICKEN EXPOSED TO CHRONIC HEAT STRESS

The aim of this research was to know histopathological changes of kidney of broiler chicken exposed to chronic heat stress. Twenty broilers were divided randomly into 2 groups, 10 broilers each are being exposed to chronic heat stress for 21 days. The first 21 days were the adaptation period in a chamber with temperature 24-28o C and humidity 40-55%. After 21 days, continue with exposure to heat stress in a chamber with temperature 36-40o C and humidity 50-65% in 8 hours per day. After exposed to chronic heat stress, kidney tissues were processed, and kidney tissue histopathological changes were evaluated by using the Klopfleisch modified scoring method. The data was analyzed by Mann – Whitney Test. The result of this research showed that chronic heat stress exposure causing the presence of degeneration of tubular epithelial cell, necrosis of tubular epithelial cell, necrosis of glomerular and interstitial infiltration. From the analysis data the overviewof multiparametric showed that when control group compared with the treatment group showed significantly difference (p&lt;0.05).

Investigation of antioxidant effects of rosmarinic acid on liver, lung and kidney in rats: a biochemical and histopathological study.

The aim of the study was to investigate the protective effects of rosmarinic acid in rats exposed to hepatic ischaemia/reperfusion (I/R) injury. Thirty-two rats were randomly classified into four groups of 8 rats each: laparotomy without medication, rosmarinic acid (dose of 50 mg/kg via oral gavage) followed by laparotomy, laparotomy followed by hepatic I/R, and hepatic I/R with rosmarinic acid. Serum aspartate aminotransferase, alaninę aminotransferase, and malondialdehyde levels and total oxidant activity and total antioxidant capacity levels of the liver, lung, and kidney were assessed. The histopathologic assessment was also performed. Rosmarinic acid significantly reduced liver function test parameters and decreased oxidative stress and abnormal histopathologic findings in the liver. The oxidative stress in the lung significantly increased in the I/R group but significantly decreased in the I/R + rosmarinic acid group due to the addition of rosmarinic acid. Rosmarinic acid led to no reduction in oxidative stress in kidney following hepatic I/R injury. There were no statistically significant differences among the groups regarding histopathologic changes in kidney and lung sections. Rosmarinic acid has antioxidant properties and is an effective hepatoprotective agent. However, although rosmarinic acid provides useful effects in the lung by increasing antioxidant capacity and reducing oxidative stress after I/R injury, it does not ameliorate histopathologic changes. These findings suggest that rosmarinic acid is likely to provide favourable outcomes in the treatment of hepatic I/R injury.

Protective Therapy with Mitochondria Isolated from Mesenchymal Stromal Cells in a Sepsis Model

Background & Aim In vivo mitochondrial transfer of mesenchymal stromal cells (MSCs) to immune cells, alveolar and bronchial epithelial cells resulted in metabolic and functional improvements. Thus, we hypothesized that naked mitochondria isolated from MSCs can be internalized by pulmonary structural cells and could be used as systemic therapy in a sepsis model. Methods, Results & Conclusion MSCs-derived mitochondria were incubated with septic murine lung endothelial and epithelial cells. Mitochondrial internalization was assessed by fluorescence microscopy, and its impact on oxidative stress and cellular respiration were evaluated. C57Bl6 mice were divided into control group, sepsis group (CLP, cecal ligation and puncture) and sepsis group with mito-treatment (CLP-mito, intravenous administration of mitochondria derived from 3 × 106 MSCs, 24 hours after CLP). The effects on mortality, pulmonary function and morphometry, liver and kidney histopathological and molecular changes were evaluated after 24 hours of mito-treatment. Mitochondria internalization by septic endothelial and epithelial cells led to reduce oxidative stress which was increased by 250% in endothelial cells and 150% in epithelial cells in CLP mice compared to control. Likewise, by oxygraphy, we analyzed the rate of oxygen consumption (OCR) of these cells. We have seen that, in epithelial cells, only maximal (MR) repolarization was reduced by about 30% after sepsis. In endothelial, both basal (BR) and maximal respiration (MR) were reduced by 50 and 48% respectivelly after sepsis, as well as a significant increase in the proton-leak (PL) rate in relation to the control group (33%). In both cell types, the altered parameters were re-established at control levels after mitocondrial treatment. Mito-treatment induced higher survival rates (60%) and reduced lung elastance (24%). Lung morphometry analysis demonstrated that mito-treatment reversed increases found in septic animals in alveolar collapse (230%), lung neutrophils (90%), lung collagen collagen (300%), elastogenesis (38%). Histological analysis of the liver demonstrates the increase of vacuolization (210%) and inflammatory infiltrate (105%) in septic animals, which were completely normalized after mito-treatment. Treatment also improved sepsis-induced kidney brush border damage (350%) and interstitial edema (205%). This work demonstrates the ability to internalize mitochondria isolated from MSCs by structural cells and the therapeutic potential of mito-treatment in a sepsis model.

Urine kidney safety biomarkers improve understanding of indirect intra-renal injury potential in dogs with a drug-induced prerenal azotemia

Drug-induced kidney injury (DIKI) is a frequent occurrence in nonclinical drug development. It is well established that novel urine kidney safety biomarkers will outperform urea nitrogen (BUN) and serum creatinine (sCr) for monitoring direct drug injury to the kidney across numerous compounds spanning diverse mechanisms and efforts are underway for a formal regulatory clinical qualification. However, it remains unclear how these novel biomarkers will perform under prerenal azotemia when BUN and sCr are elevated but no intra-renal injury is suspected. This lack of knowledge is largely due to the dearth of such nonclinical animal models. We report here that treatment of dogs with a potent antihypertensive compound MK-5478 at a suprapharmacologic dose for up to 9 days results in the development of prerenal azotemia and, in some dogs, kidney toxicity through the dual sustained effects of MK-5478 as a nitric oxide donor and an angiotensin II receptor blocker (ARB). While conventional serum biomarkers BUN, and often sCr as well, were highly elevated in these dogs with or without kidney damage, urine kidney biomarkers clusterin (CLU) and neutrophil gelatinase-associated lipocalin (NGAL) showed increases only in dogs with kidney histopathologic changes following the sustained period of prerenal azotemia. Urine albumin (ALB) and total protein also tracked with kidney lesions but with less sensitivity. Thus, we present evidence for the first time that urine kidney safety biomarkers used together with BUN and sCr can distinguish intra-renal injury among dogs with prerenal azotemia while the conventional serum biomarkers alone are ambiguous, either being interpreted as false positives of kidney injury, or dismissed under circumstances as benign without appreciation for a threshold of impending injury.

2, 4- Dichlorophenoxy acetic acid induced Histopathological changes in kidney of Clarias batrachus

2, 4- Dichlorophenoxy acetic acid induced Histopathological changes in kidney of Clarias batrachus

Protective Effect of Diosgenin on Streptozotocin Induced Diabetic Nephropathy in Experimental Rats

Diabetes mellitus is a multifactorial metabolic disorder associated with the diabetes related vascular diseases. Oxidative stress along with inflammation is the Key factor leading to diabetic complications. Present study was designed to investigate the protective role of diosgenin, a steroidal saponin, in diabetes induced early kidney injury and oxidative stress markers and histopathological changes in kidney of diabetic rats, induced by single intra-peritoneal injection of streptozotocin (55 mg/kg weight (b.w.). After 72 hrs, experimental rats received diosgenin at different doses (10, 20 and 40 mg/kg b.w.) once daily for four weeks. At the end of the experiment, diabetic rats showed a significant increase in the levels of plasma glucose, glycosylated hemoglobin with a significant decrease in insulin and total hemoglobin. The activities of antioxidant enzymes such as superoxide dismutase, catalase, reduced glutathione, and the levels of reduced glutathione were decreased while increases in the levels of lipid peroxidation markers were observed in kidney tissues of diabetic rats. Oral administration of diosgenin to diabetic rats considerably shrivelled the plasma glucose and exaggerated the endocrine level supported a dose dependent manner. Diosgenin at a dose of 40 mg/kg b.w. was more pronounced effect than the other two doses and used for further studies. All the manifestations observed in diabetic rats were significantly reversed to near normal at a dose of 40 mg/kg b.w. of diosgenin. These findings recommend that diosgenin may have a helpful role against excretory organ harm evoked by aerobic stress within the diabetic state.

Gentamicin Nephrotoxicity in Animal Model: Study of Kidney Histopathology and Physiological Functions

The purpose of this study was to analyze abnormal changes in kidney histology and physiology in acute kidney injury animal models with multiple doses of gentamicin. Induction of experimental animals was carried out on 20 rats (Rattus norvegicus) Wistar strain which were divided into 4 groups, group I was a negative control group, groups II, III and IV are gentamicin-induced groups at doses of 30 mg/kg, 40 mg/kg, and 50 mg/kg, respectively. Kidney histopathology were stained with Hematoxylin Eosin (HE), while analysis of serum BUN and creatinine by spectrophotometric method. Data analysis for kidney histopathology was descriptively while for BUN and Creatinine were statistically tested with one way ANOVA. The results of this study showed there was a kidney damage in all gentamicin-induced groups, which is necrosis in the contortus tubule and the Bowman’s capsule compared to the negative control group. The group of rats with the higher doses of gentamicin showed a more severe level of histopathological changes, however, BUN and creatinine levels were not significantly different (p> 0.05). This study concludes that gentamicin induction could cause kidney histopathological changes but not kidney physiology.

Chaiqin chengqi decoction alleviates severe acute pancreatitis associated acute kidney injury by inhibiting endoplasmic reticulum stress and subsequent apoptosis

BackgroundAcute kidney injury (AKI), characterized by an increase of serum creatinine and urea, is a severe complication of severe acute pancreatitis (SAP) with high mortality. Endoplasmic reticulum (ER) stress has been considered as a key pathologic process in AKI. Chaiqin chengqi decoction (CQCQD) is an effective Chinese medicine formula for SAP treatment in China and has been used for many years. Our goal is to explore the role of CQCQD on ER stress of AKI in experimental SAP. Materials & methodsSAP was induced in rats by retrograde duct injection of 5% sodium taurocholate (NaTC, 1 ml/kg), sham operation (SO) rats simultaneously received saline infusion. Intraperitoneal injection of 4-PBA (50 mg/kg, once a day for three days before the surgery) or intragastric gavage of CQCQD (1 g/kg, 2 hourly × 3 after disease induction) was used to treat SAP rats. All animals were humanely sacrificed 12 h after disease induction. Histopathology scores of kidney and pancreas; serum biochemical indices and kidney protein levels of ER stress and apoptosis markers were assessed. Tubular epithelial cell line (HK-2) was treated either with TNF-α (10 ng/ml) or IL-6 (10 ng/ml) for 12 h plus either 4-PBA (0.1 M) or CQCQD (1 mg/ml) for in vitro study. Cell viability and markers of ER stress and apoptosis were measured. ResultsDuctal perfusion of NaTC caused significant increases in serum lipase, amylase and pancreatic histopathology (inflammatory cell infiltration, interstitial edema, and acinar cell necrosis). Kidney histopathology (tubular dilation, brush border loss, little tubular necrosis, and cast formation), serum creatine and urea levels were raised when compared with the SO group. Moreover, apoptotic cell death markers (caspase-9, cleaved-caspase-3, and TUNEL) and kidney ER stress proteins (BIP, IRE1-α, XBP1s, and CHOP) were elevated after NaTC administration. 4-PBA and CQCQD significantly alleviated histopathological changes of kidney and pancreas, inflammatory cytokines, biochemical markers of AKI, ER stress proteins and apoptotic cell death markers. They also protected HK-2 cells from injury of TNF-α and IL-6, and alleviated both ER stress and apoptosis proteins in vitro. ConclusionCQCQD may alleviate SAP-related AKI by inhibiting ER stress-related apoptosis.

MiR-20a ameliorates diabetic angiopathy in streptozotocin-induced diabetic rats by regulating intracellular antioxidant enzymes and VEGF.

We evaluated the beneficial effect of miR-20a mimic against diabetic angiopathy (DA) in rats by regulating intracellular antioxidant enzymes and vascular endothelial growth factor (VEGF). Diabetes was induced by intraperitoneal administration of streptozotocin (STZ; 65 mg/kg). Rats were then treated with miR-20a mimic (250 nmol/kg orally) for 8 weeks after STZ administration. The effect of miR-20a mimic against DA in rats was evaluated by estimating serum glucose concentration, lipid profile, Lp-a, kidney function test, inflammatory mediators, and markers of endothelial cell function. Markers of oxidative stress in the aortic tissue were estimated in rats treated with miR-20a mimic. Western blot assay, RT-PCR, and histopathology of kidney and myocardial tissues were also performed. Serum levels of blood glucose and markers of renal function were significantly lower, and the lipid profile improved in the miR-20a mimic group compared to the DA group. Treatment with miR-20a mimic ameliorated the altered markers of endothelial function and oxidative stress, as well as mediators of inflammation, in the DA rats. Protein expressions of ERK1/2, JNK, and p38 MAPK, as well as mRNA expressions of TLR-4 and NF-κB, in aortic tissues were lower in the miR-20a mimic group than in the DA group. The miR-20a mimic group had fewer histopathological changes in kidney and myocardial tissues than the DA group. MiR-20a mimic can protect against DA in rats by regulating vascular endothelial function and oxidative stress.

Licorice Extracts Attenuate Nephrotoxicity Induced by Brucine Through Suppression of Mitochondria Apoptotic Pathway and STAT3 Activation.

Licorice, one of the most widely used medicinal herbs in East Asia, has effects such as anti-inflammation, antioxidant, and detoxifying. This study aimed to evaluate the protective effect of licorice on brucine-induced nephrotoxicity. Sprague Dawley rats were administered with brucine intraperitoneally for 7 consecutive days with or without treatment with licorice. The content of blood urea nitrogen and creatinine in serum, the activities of superoxide dismutase and content of glutathione, malonaldehyde in kidney tissue were detected. Hematoxylin-eosin staining was employed to observe the histopathological changes of kidney. The expression and phosphorylation levels of protein were evaluated by Western blotting and immunohistochemical analysis. The results illustrated that treatment with licorice extracts (LE) significantly protected against the brucine-induced nephrotoxicity by reducing the content of blood urea nitrogen and serum creatinine, attenuating pathologic damage. The unbalance of oxidative stress was repaired by LE via increasing the level of glutathione, promoting the activities of superoxide dismutase and decreasing the content of malonaldehyde. In addition, LE overturned the influence of brucine on apoptosis-related protein and signal transducer and activator of transcription-3 (STAT3) activation. Taken together, these data demonstrate that licorice may attenuate brucine-induced nephrotoxicity via inactivation of oxidative stress and mitochondrial-mediated apoptosis pathway. More importantly, the renoprotective effects may be mediated, at least partly, by preventing the activation of STAT3 protein.

Clock gene Bmal1 alleviate ischemia-reperfusion injury in transplanted kidney by regulate peroxisome proliferator activated receptor α/peroxisome proliferator activated receptor coactivator-1α pathway

Objective This study was to investigate the effect of clock gene Bmal1 on ischemia-reperfusion injury in transplant kidney (TK) and relationship with peroxisome proliferator activated receptor α (PPARα)/peroxisome proliferator activated receptor coactivator-1α (PGC-1α) pathway. Methods Twenty-four male Sprague-Dawley rats were randomly divided into 4 groups: sham operation group, TK group, Bmal1 short hairpin RNA (shRNA) group, Bmal1 shRNA+ fenofibrate group. Each group was given appropriate intervention and took specimens. The levels of serum creatinine (Cr) and urea nitrogen (BUN) were measured. The histopathological changes of kidneys in each group were estimated by hematoxylin and eosin (HE) staining. Western blotting was used to detect the expression of Bmal1, PPARα, PGC-1α, bcl-2/bax in kidney tissue. The amount of adenosine triphosphate (ATP) produced was determined by using colorimetric kit. SPSS 17.0 software was used for statistical analysis. The measurement data were expressed as mean±standard deviation. The comparison between two groups was analyzed with Student’s t test. The comparison among three or more groups was performed by one-way ANOVA test. Results Compared with the sham operation group (73.5±6.7, 8.2±0.7, 2.16±0.20, 3.15±0.29, 6.28±0.42, 2.09±0.22, 29.33±3.14), the serum Cr (211.0±17.4) and BUN levels (44.0±3.8) and renal tissue damage were increased (t=18.063, 22.695, P<0.05), while the expression of Bmal1 (1.63±0.17), PPARα (2.52±0.20), PGC-1α (4.65±0.37), bcl-2/bax (1.22±0.14) and ATP production (15.34±1.02)were decreased (t=4.946, 4.450, 7.133, 8.172, 10.380, P<0.05) in the TK group. Compared with the TK group, Bmal1 shRNA group showed increased Cr (307.0±28.9) and BUN (53.0±4.2) levels and renal tissue damage was increased (t=6.971, 3.892, P<0.05), but decreased expression of Bmal1 (1.30±0.11), PPARα (2.01±0.23), PGC-1α (3.86±0.20), bcl-2/bax (0.76±0.06) and ATP production (10.15±0.96) (t=3.992, 4.099, 4.601, 7.398, 9.076, P<0.05). Compared with Bmal1 shRNA group, the serum Cr (241.3±20.2) and BUN levels (47.0±4.5) and renal tissue damage were decreased (t=4.564, 2.388, P<0.05), while the expression of Bmal1 (1.55±0.10), PPARα (2.48±0.17), PGC-1α (4.36±0.25), bcl-2/bax (1.10±0.11) and ATP production (14.71±1.21) were increased (t=4.119, 4.025, 3.826, 6.647, 29.572, P<0.05) in Bmal1 shRNA+ fenofibrate group. Conclusion The clock gene Bmal1 protects against I/R injury in transplanted kidney via regulate PPARα/PGC-1α pathway. Key words: Transplanted kidney; Renal ischemia-reperfusion injury; Energy metabolism; Bmal1; Peroxisome proliferator activated receptor α/peroxisome proliferator activated receptor coactivator-1α

Renoprotective Effects Of Isoliquiritin Against Cationic Bovine Serum Albumin-Induced Membranous Glomerulonephritis In Experimental Rat Model Through Its Anti-Oxidative And Anti-Inflammatory Properties.

BackgroundMembranous glomerulonephritis (MGN) is a nephrotic syndrome which shows the symptoms of heavy proteinuria and immune complex deposition in glomerular sub-epithelial space and finally leads to chronic kidney disease. Isoliquiritin (ILQ) is a flavonoid with a wide range of pharmacological properties, including antioxidant and anti-inflammatory activity. The present study was undertaken to investigate the possible mechanisms by which ILQ ameliorates cationic bovine serum albumin (C-BSA) induced MGN in rat model.MethodsThe MGN condition was confirmed by the 24 hr proteinuria and ILQ (10 mg/kg/bw/day) or TPCA-1 (10 mg/kg/bw/day; IKKβ inhibitor) was administered to successfully induce rats for 4 weeks.ResultsThe present study revealed that MGN rats treated with ILQ showed significantly ameliorated kidney dysfunction and histopathological changes in kidneys. ILQ treated MGN rats alleviated the oxidative stress and were presented with increased anti-oxidative status in kidneys. Furthermore, ILQ treatment to MGN rats showed anti-oxidative effects through the prominent stimulation of Nrf2 signaling pathway and inhibition of Keap1, which consequently increases the Nrf2 nuclear translocation and thereby induces expression of NQO1 and HO-1. In addition, ILQ-treated MGN rats demonstrated anti-inflammatory effects by inhibiting NF-κB signaling pathway through decreased mRNA and protein expressions of NF-κB p65, IKKβ, COX-2, iNOS, p38-MAPK, p-p38-MAPK, TNF-α, IL-1β, IL-8, ICAM-1, E-selectin and VCAM-1 and reduced the nuclear translocation of NF-κB p65.ConclusionThe protective effect of ILQ on MGN can be explained by its anti-oxidative and anti-inflammatory activities, which in turn due to the activation of Nrf2 and downregulation of NF-κB pathway.