scholarly journals Antioxidant protection of statins in acute kidney injury induced by sepsis

2014 ◽  
Vol 48 (5) ◽  
pp. 820-826 ◽  
Author(s):  
Franciele do Nascimento Santos ◽  
Mirian Watanabe ◽  
Carolina Ferreira Vasco ◽  
Cassiane Dezoti da Fonseca ◽  
Maria de Fatima Fernandes Vattimo
Keyword(s):  
Acute Kidney Injury ◽  
Wistar Rats ◽  
Kidney Injury ◽  
Sham Control ◽  
Male Adult ◽  
Animal Survival ◽  
Oxidative Metabolites ◽  
Lower Severity ◽  
Control Sham ◽  
Fluid Culture

Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control); SHAM+Statin (0.5 mg/kg simvastatin, orally); Sepsis (cecal puncture ligation – CPL); Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

scholarly journals Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury

2021 ◽  
Vol 22 (3) ◽  
pp. 1382
Author(s):  
Jelena Nesovic Ostojic ◽  
Milan Ivanov ◽  
Nevena Mihailovic-Stanojevic ◽  
Danijela Karanovic ◽  
Sanjin Kovacevic ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protein Expression ◽  
Hyperbaric Oxygen ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Kidney Injury ◽  
Heme Oxygenase 1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

Abstract 655: Ischemia-induced Epoxyeicosatrienoic Acid Release Protects Female Rats From Acute Kidney Injury

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Duska Dragun ◽  
Uwe Hoff ◽  
Maximilian Blum ◽  
Gordana Bubalo ◽  
Mandy Fechner ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Creatinine Clearance ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Female Rats ◽  
Epoxyeicosatrienoic Acid ◽  
Renal Protection ◽  
Sham Control ◽  
Male And Female ◽  
Enhanced Production

Females are naturally protected against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) in various clinical and experimental settings. However, the underlying mechanisms are unknown. We hypothesized that female protection may be conferred by enhanced production of cytochrome P450 (CYP)-dependent epoxyeicosatrienoic acids (EETs) that promote vasodilation as well as antiinflammatory and antiapoptotic pathways in the kidney. To test this hypothesis, we first analyzed the renal CYP-eicosanoid profile by liquid chromatography tandem mass spectrometry in male and female Lewis rats. Ischemia was induced through 45 min of left renal vessel clamping after right nephrectomy (n=6-8 per group). In non-ischemic controls, male and female kidneys stored almost identical amounts of EETs as well as 20-hydroxyeicosatetraenoic acid (20-HETE), both predominantly esterified into phospholipids, under basal non-ischemic conditions. 45 min of ischemia induced a massive release of EETs from membrane stores in females but not males. The free renal EET-levels reached 70.2±20.1 in females compared to only 4.6±1.3 ng/g in males. After ischemia, the ratio of free EETs to free 20-HETE was about 1:1 in females and 1:3 in males. Next, we proved the functional importance of EETs in renal protection by pretreating males with a synthetic EET-agonist (12-HUDE) and females with a selective EET-antagonist (14,15-EEZE-mSI). As analyzed two days after reperfusion, the EET-agonist protected males against loss of creatinine clearance (1.03±0.18 vs. 0.26±0.02 ml/min, p<0.01 vs. vehicle, compared to 1.28±0.06 ml/min in sham control). Females were rendered susceptible to I/R-injury by the EET-antagonist (creatinine clearance: 0.25±0.05 vs. 0.67±0.04; p<0.01 vs. vehicle, compared to 0.81±0.04 ml/min in sham control). Changes in inflammatory cell infiltration and tubular apoptosis paralleled these effects on renal function. Our results indicate that female rats are protected against renal I/R-injury by enhanced ischemia-induced EET-release and demonstrate that renal protection can be transferred to males using synthetic EET-agonists.

scholarly journals Urinary N-Acetyl-Beta-D-Glucosaminidase Activity in Rat Experimental Ischemic and Toxic Models of Acute Kidney Injury

2017 ◽  
Vol 74 (1) ◽  
pp. 105
Author(s):  
Razvan Andrei CODEA ◽  
Mircea MIRCEAN ◽  
Sidonia Alina BOGDAN ◽  
Andras Laszlo NAGY ◽  
Alexandra BIRIS ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Experimental Model ◽  
Wistar Rats ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Control Group ◽  
Tubular Injury ◽  
Group 2 ◽  
Group 1

The identification of a suitable prevention method which facilitates limiting the deleterious effects of acute kidney injuries is highly required. In order to identify a proper treatment for acute kidney injuries, a suitable experimental model that replicates the structural, metabolic and inflammatory lesions that occur in the natural acute injured kidney is highly necessary. Intense urinary NAG activity can be found in a variety of renal disease such as toxic nephropathies, ischemic renal injury following cardiac surgery or renal transplantation but also in glomerular disease especially in diabetic nephropathy. Rises in urinary NAG enzyme activity strongly suggests tubular cell damage and support NAG enzyme as a biomarker of renal tubular injury. The aim of this paper is to obtain a stable in vivo acute kidney injury experimental model, in Wistar, rats and to evaluate the urinary activity of N-acetyl-β-D-glucosaminidase (NAG) enzyme, blood levels of urea and creatinine and microstructural renal alterations induced by ischemia/reperfusion injury respectively gentamicin nephrotoxicity. For this purpose we have used a rat experimental model. Adult male Wistar rats weighing 250-300 g were randomly divided into 3 groups with 8 rats in each group. Group 1 served as a model for the renal ischemia/reperfusion injury experiment, group 2 served for toxic kidney injury experimental model and group 3 served as control group. All individuals in both groups 1 and 2 presented marked elevations in blood urea and creatinine at the moment of euthanasia (day 3 for group 1 and day 9 for group 2) compared to the control group where biochemical values remained within normal limits. Urine analysis of both group 1 and 2 showed marked urinary NAG index activity which suggests acute tubular injury, suggestion confirmed by histological evaluation of the renal parenchyma sampled from this subjects

scholarly journals Nephrotoxic drug burden among 1001 critically ill patients: impact on acute kidney injury

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stephan Ehrmann ◽  
◽  
Julie Helms ◽  
Aurélie Joret ◽  
Laurent Martin-Lefevre ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Acute Kidney Injury ◽  
Intensive Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Drug Prescription ◽  
Kidney Injury ◽  
Simplified Acute Physiology Score ◽  
Severity Of Disease ◽  
Lower Severity

Abstract Background Nephrotoxic drug prescription may contribute to acute kidney injury (AKI) occurrence and worsening among critically ill patients and thus to associated morbidity and mortality. The objectives of this study were to describe nephrotoxic drug prescription in a large intensive-care unit cohort and, through a case–control study nested in the prospective cohort, to evaluate the link of nephrotoxic prescription burden with AKI. Results Six hundred and seventeen patients (62%) received at least one nephrotoxic drug, among which 303 (30%) received two or more. AKI was observed in 609 patients (61%). A total of 351 patients were considered as cases developing or worsening AKI a given index day during the first week in the intensive-care unit. Three hundred and twenty-seven pairs of cases and controls (patients not developing or worsening AKI during the first week in the intensive-care unit, alive the case index day) matched on age, chronic kidney disease, and simplified acute physiology score 2 were analyzed. The nephrotoxic burden prior to the index day was measured in drug.days: each drug and each day of therapy increasing the burden by 1 drug.day. This represents a semi-quantitative evaluation of drug exposure, potentially easy to implement by clinicians. Nephrotoxic burden was significantly higher among cases than controls: odds ratio 1.20 and 95% confidence interval 1.04–1.38. Sensitivity analysis showed that this association between nephrotoxic drug prescription in the intensive-care unit and AKI was predominant among the patients with lower severity of disease (simplified acute physiology score 2 below 48). Conclusions The frequently observed prescription of nephrotoxic drugs to critically ill patients may be evaluated semi-quantitatively through computing drug.day nephrotoxic burden, an index significantly associated with subsequent AKI occurrence, and worsening among patients with lower severity of disease.

scholarly journals Ferrotoxicity and its amelioration by endogenous vitamin D in experimental acute kidney injury

2020 ◽  
Vol 245 (16) ◽  
pp. 1474-1489
Author(s):  
Chandrashekar Annamalai ◽  
Rajesh N Ganesh ◽  
Pragasam Viswanathan
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Acute Kidney Injury ◽  
Wistar Rats ◽  
Kidney Injury ◽  
Urinary Ngal ◽  
Tissue Lipid ◽  
Dihydroxyvitamin D3 ◽  
Tissue Lipid Peroxidation ◽  
Serum And Urine

Acute kidney injury causes significant morbidity and mortality. This experimental animal study investigated the simultaneous impact of iron and vitamin D on acute kidney injury induced by iohexol, an iodinated, non-ionic monomeric radiocontrast agent in Wistar rats. Out of 36 healthy male Wistar rats, saline was injected into six control rats (group 1) and iohexol into the remaining 30 experimental rats (groups 2 to 6 comprising six rats each). Biochemical, renal histological changes, and gene expression of iron-regulating proteins and 1 α-hydroxylase were analyzed. Urinary neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine, urine protein, serum and urine catalytic iron, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and tissue lipid peroxidation were assayed. Rats injected with iohexol showed elevated urinary NGAL (11.94 ± 6.79 ng/mL), serum creatinine (2.92 ± 0.91 mg/dL), and urinary protein levels (11.03 ± 9.68 mg/mg creatinine) together with histological evidence of tubular injury and iron accumulation. Gene expression of iron-regulating proteins and 1 α-hydroxylase was altered. Serum and urine catalytic iron levels were elevated (0.57 ± 0.17; 48.95 ± 29.13 µmol/L) compared to controls (0.49 ± 0.04; 20.7 ± 2.62 µmol/L, P < 0.001). Urine catalytic iron positively correlated with tissue peroxidation (r = 0.469, CI 0.122 to 0.667, P = 0.004) and urinary NGAL (r = 0.788, CI 0.620 to 0.887, P < 0.001). 25-hydroxyvitamin D3 (61.58 ± 9.60 ng/mL) and 1,25-dihydroxyvitamin D3 (50.44 ± 19.76 pg/mL) levels increased simultaneously. In a multivariate linear regression analysis, serum iron, urine catalytic iron, and tissue lipid peroxidation independently and positively predicted urinary NGAL, an acute kidney injury biomarker. This study highlights the nephrotoxic potential of catalytic iron besides demonstrating a concurrent induction of vitamin D endogenously for possible renoprotection in acute kidney injury. Impact statement This work provides in-depth insights on catalytic iron-induced cytotoxicity and the resultant triggering of endogenous vitamin D synthesis in experimental acute kidney injury. Our results reveal significantly elevated levels of catalytic iron culminating in oxidant-mediated renal injury and a concomitant increase in 1,25-dihdyroxyvitamin D3 levels. Also, changes in other iron-related proteins including transferrin, ferritin, and hepcidin were observed both in the serum as well as in their mRNA expression. We consider all these findings vital since no connection between catalytic iron and vitamin D has been established so far. Furthermore, we believe that this work provides new and interesting results, with catalytic iron emerging as an important target in ameliorating renal cellular injury, possibly by timely administration of vitamin D. It also needs to be seen if these observations made in rats could be translated to humans by means of robust clinical trials.

scholarly journals Nephroprotective Effects of L-Arginine against Chemotherapy Induced Acute Kidney Injury in Wistar Rats

2020 ◽  
Vol 9 (4) ◽  
pp. 249-255
Author(s):  
Dr.Kumayl Abbas Meghji ◽  
Dr.Tariq Feroz Memon ◽  
Dr. Imtiaz Ahmed ◽  
Dr. Sehar Gul Memon ◽  
Dr. Naila Noor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Wistar Rats ◽  
Kidney Injury ◽  
Control Group ◽  
P Value ◽  
Renal Histology ◽  
Renal Markers ◽  
Group B ◽  
Experimental Group

Objective To evaluate the protective role of L-Arginine in cisplatin induced acute renal injury through assessment of renal, oxidative stress and inflammatory markers in albino wistar rats. Methods: Quasi-experimental study was conducted at the department of physiology and postgraduate research laboratory at Isra University, Hyderabad, Sindh from April 2019 to September 2019. Thirty male Albino wistar rats were selected through non-random purposive sampling and divided equally into three different groups: Group-A (Control group), Group-B (experimental group) received Cisplatin alone and Group-C (experimental group) received Cisplatin along with arginine. After sacrificing the animals, blood samples were collected through cardiac puncture while renal histopathological analysis was under the light microscope. The changes in severity were observed using a graded scale. Data was analysed using SPSS v23.0. Results: There was a statistically significant (p-value <0.05) decline in the bodyweight and rise in absolute kidney weight of group B in comparison with other two group. Moreover, significant rise (p-value <0.05) in serum renal markers was observed in group B while significant decline (p-value <0.05)  in these serum renal markers in group C compared with group B.  Furthermore, prominent demage in normal renal histology in group B rats while restoration of renal histology was demonstrated in group C rats. Conclusion: The present study concludes that L-Arginine exerts an anti-oxidative, anti-inflammatory and nephro-protective effect for renal tissue damage caused by Cisplatin. Keywords: Acute Kidney Injury, Antioxidant, Cisplatin, L-Arginine, Oxidative stress

REVISITING THE ACUTE KIDNEY INJURY IN WISTAR RATS EXPERIMENTALLY ENVENOMATED WITY Bothrops jararacussu VENOM.

Toxicon ◽  
2021 ◽  
Author(s):  
Mayara A. Romanelli ◽  
Paula A. Soeiro ◽  
Raquel Costa da Silva ◽  
Rosilane Taveira-da-Silva ◽  
Paulo A. Melo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Wistar Rats ◽  
Kidney Injury ◽  
Bothrops Jararacussu

Immunomodulatory response and serum level of neutrophil gelatinase associated lipocalin (NGAL) as a marker of acute kidney injury in wistar rats exposed to pyrethroids

2021 ◽  
pp. 1-11
Author(s):  
Adedeji David Atere ◽  
Olumide Faith Ajani ◽  
Akinpelu Moronkeji ◽  
Victory Oluwaseun Ajibade ◽  
Humphrey Benedo Osadolor
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Uric Acid ◽  
Wistar Rats ◽  
Vena Cava ◽  
Kidney Injury ◽  
Total Antioxidant Status ◽  
Immune Functions ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Neutrophil Gelatinase

BACKGROUND: Insecticide usage has increased in the tropics and subtropics due to the high prevalence of vector-borne infections, even though insecticide use effectively reduces insect-borne diseases. Insecticide exposure can cause oxidative stress and have severe consequences for human health. The study was then designed to evaluate oxidative stress and its effects on immunomodulatory and renal integrity among Wistar rats exposed to pyrethroids. METHODS: Eighty-four Wistar rats were randomly selected and divided into two groups. Fifty-one rats were exposed to 1.2 %w/v pyrethroids, while the remaining thirty-three rats were grouped as non-exposed. The groups were divided into three different groups, each with 7, 21, and 41 days. After days of exposure, the animals in each group were anesthetized, and blood samples were collected from the inferior vena cava. Using standard spectrophotometric techniques, the levels of total antioxidant status (TAS), malondialdehyde (MDA), glutathione (GSH), hydrogen peroxide (H2O2), urea, creatinine and uric acid were determined. Blood activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were determined. ELISA was used to determine levels of IgG, IgA, IgE, TNF-α, and NGAL. Data obtained were statistically compared. RESULTS: The serum mean levels of SOD, GPx, CAT, GSH, and TAS were significantly reduced (p <  0.05) while mean levels of MDA, H2O2, IgG, IgE, IgA, TNFα, neutrophil gelatinase-associated lipocalin (NGAL), urea, uric acid, and creatinine were significantly elevated (p <  0.05) from 7 to 41 days exposure in exposed groups. NGAL had a higher area under the ROC curve than urea and creatinine. CONCLUSIONS: This study observed that pyrethroids can cause oxidative stress, deplete antioxidant levels, nephrotoxicity, and may modulate both humoral and cellular immune functions. It also established NGAL as a sensitive diagnostic tool and early biomarker for acute kidney injury (AKI).

The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Kidney Injury and Its Mechanisms

2021 ◽  
Vol 11 (2) ◽  
pp. 265-270
Author(s):  
Xiaobo Zhang ◽  
Ying Zhu ◽  
Ying Zhou ◽  
Bingru Fei
Keyword(s):  
Acute Kidney Injury ◽  
Western Blot ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Protective Effects ◽  
Serum Cystatin C ◽  
Hematoxylin And Eosin ◽  
Underlying Mechanisms ◽  
Control Sham

MG-132 is an aldehyde peptide proteasome inhibitor, which reduces the inflammatory response and exerts a protective effect on severe acute pancreatitis and associated lung injury of rats. However, the involvement of MG-132 in sepsis-induced acute kidney injury (AKI) and the underlying mechanisms remain unknow. In this study, SD rats were employed to induce sepsis by cecal ligation and puncture (CLP) method and then divided into control, sham, CLP, and CLP + MG-132. Histopathology observation was detected by hematoxylin and eosin staining. The levels of biomarkers representing renal function such as serum creatinine (Scr), blood urea nitrogen (BUN), serum cystatin C (Scys C), and indicators of AKI such as Kim-1, IL-18, α glutathione S-traferase (α-GST) and albumin were measured by ELISA. Western blot and immunohistochemistry were performed to measure Testican-1. In order to assess the role of Testican-1, the expression of β-catenin, c-myc and cyclinD1 were evaluated by western blot. The results indicated that the levels of SCr, BUN, Scys C, KIM-1, IL-18, GST-α and albumin were decreased after MG-132 treatment compared with CLP group. And both pathological injury and W/D ratio were obviously improved in the CLP + MG- 132 group. Furthermore, the level of Testican-1 increased in the CLP group while a decreased presented in the CLP + MG-132 group. The expression of β-catenin, c-myc and cyclinD1 were downregulated in the CLP + MG-132 group compared to the CLP group. Our findings suggested that MG-132 can protect against AKI via inhibiting Testican-1 through the Wnt/β-catenin pathway MG-132 served as a novel biomarker and therapeutic regimen for sepsis-induced AKI.

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