scholarly journals Angiotensin (1-7) Attenuates Sepsis-Induced Acute Kidney Injury by Regulating the NF-κB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ying Zhu ◽  
Daliang Xu ◽  
Fang Deng ◽  
Yonglin Yan ◽  
Jian Li ◽  
...  

This study explores the protective mechanism of angiotensin (1-7) [Ang-(1-7)] on kidneys by examining its effects on renal histomorphology, inflammatory response, oxidative stress, and NF-κB signaling in mice suffering from sepsis-induced acute kidney injury. A sepsis-induced acute kidney injury mouse model was established by intracervically injecting lipopolysaccharides (LPS group), followed by the administration of Ang-(1-7) [LPS + Ang-(1-7) group]. The serum levels of urea nitrogen, creatinine and cystatin. c were measured with an automatic biochemical analyzer, and changes in proinflammatory cytokines and angiotensin II (Ang II) in the serum and kidneys were quantified by enzyme-linked immunosorbent assays. Changes in oxidative stress indices in the renal cortex were detected by colorimetry. The localization of Ang II in kidneys was examined by immunohistochemistry. Western blotting was used to examine phosphorylated NF-κB-p65 and IκBα levels in kidneys. Compared with the control group, the serum levels of urea nitrogen, creatinine and cystatin. c were increased, whereas the levels of Ang II, TNFα, IL-1β, IL-6, and malondialdehyde (mda) were increased significantly. The levels of Ang II and phosphorylated NF-κB-p65 were elevated in kidneys, whereas the levels of superoxide dismutase (sod), Total antioxidative capacity (TAOC), and inhibitor of NF-κB (IκBα) were reduced in the LPS group (p < 0.05). Pathological damage was also observed in kidneys of LPS-group mice. In Pearson correlation analysis, there was a positive correlation between Ang II and phosphorylated NF-κB-p65 levels, and a negative correlation between Ang II and IκBα levels (p < 0.05). After the application of Ang-(1-7), the levels of urea nitrogen, creatinine, cystatin. c, Ang II, TNFα, IL-1β, IL-6, and mda, as well as the expression of Ang II and phosphorylated NF-κB-p65 in kidneys of LPS + Ang-(1-7)-group mice, were lower than those in kidneys of LPS-group mice, but the levels of sod, TAOC, and IκBα were higher than those of LPS-group mice (p < 0.05). Pathological changes were less severe in mice of the LPS + Ang-(1-7) group. Overall, Ang-(1-7) can decrease the Ang II level, inhibit NF-κB signaling, reduce the inflammatory response, decrease oxidative stress, and mitigate sepsis-associated acute kidney injury.

2020 ◽  
Author(s):  
Yahya Naguib ◽  
Eman Elgizawy

Abstract Background: Acute kidney injury (AKI) or Acute renal failure (ARF) refers to the sudden damage or failure of the kidney within few hours or days and resulting in acute deterioration of the renal functions. If not properly treated, AKI may lead to chronic renal failure and possibly renal transplantation. The aim of the present study was to evaluate the role of exogenous glutathione (GSH) on ciprofloxacin (GFX)-induced AKI. We also studied the effect of glutathione administration on some genes of interest.Methods: Forty male Wistar albino rats were equally divided into 4 groups. The control group received intra-peritoneal injection of distilled water for 15 consequent days. The GSH treated group received concomitant intra-peritoneal injection of distilled water and glutathione (200 mg/kg/day) for 15 consequent days. The CFX treated group received concomitant intra-peritoneal injection of distilled water and ciprofloxacin (800 mg/kg/day) for 15 consequent days. The CFX+GSH treated group received concomitant intra-peritoneal injection of CFX and CSH for 15 consequent days. Serum levels of creatinine, urea, cystatin C and GGT were measured. Renal CYP4F1, GPx, GSR gene expression was evaluated.Results: Exogenous GSH had no significant effect on the kidney functions or the studied genes when compared to the control group. Treatment with CFX resulted in significant increase (P<0.05) in creatinine, urea, cystatin C and GGT serum levels when compared to the control group. CFX treatment also significantly (P<0.05) down-regulated renal GPx, GSR mRNA levels, while it up-regulated renal CYP4F1, when compared to the corresponding values in the control rats. Serum levels of urea, creatinine and cystatin C were significantly lower (P<0.05) in CFX+GSH group when compared to the CFX treated rats. There was significant up-regulation (P<0.05) of the renal, GPx, GSR and down-regulation of CYP4F1 mRNA levels in the CFX+GSH group when compared to the corresponding values in the CFX treated group.Conclusion: Our results suggest a potential prophylactic and possibly therapeutic roles of exogenous GSH administration in the treatment of drug-induced AKI. We also demonstrated that the underlying mechanism could be explained, at least in part, by the antioxidant and gene modifying properties of GSH.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-lei Wang ◽  
Tuo Zhang ◽  
Liu-hua Hu ◽  
Shi-qun Sun ◽  
Wei-feng Zhang ◽  
...  

Statins are a promising new strategy to prevent contrast-induced acute kidney injury (CI-AKI). In this study we compared the ameliorative effect of different statins in a rat model of CI-AKI. Sprague-Dawley rats were divided into five groups: control group; CI-AKI group; CI-AKI + rosuvastatin group (10 mg/kg/day); CI-AKI + simvastatin group (80 mg/kg/day); and CI-AKI + atorvastatin group (20 mg/kg/day). CI-AKI was induced by dehydration for 72 hours, followed by furosemide intramuscular injection 20 minutes before low-osmolar contrast media (CM) intravenous injection. Statins were administered by oral gavage once daily for 3 consecutive days before CM injection and once 4 hours after CM injection. Rats were sacrificed 24 hours after CM injection, and renal function, kidney histopathology, nitric oxide (NO) metabolites, and markers of oxidative stress, inflammation, and apoptosis were evaluated. The results showed that atorvastatin and rosuvastatin but not simvastatin ameliorated CM-induced serum creatinine elevation and histopathological alterations. Atorvastatin and rosuvastatin showed similar effectiveness against CM-induced oxidative stress, but simvastatin was less effective. Atorvastatin was most effective against NO system dysfunction and cell apoptosis, whereas rosuvastatin was most effective against inflammation. Our findings indicate that statins exhibit differential effects in preventing CI-AKI when given at equivalent lipid-lowering doses.


2019 ◽  
Vol 35 (3) ◽  
Author(s):  
Jie Ni ◽  
Hui Jiang ◽  
Fang Wang ◽  
Long Zhang ◽  
Dujuan Sha ◽  
...  

Objective: To evaluate the clinical effects of continuous intravenous infusion with high-dose furosemide on early acute kidney injury (AKI) complicated with acute lung edema. Methods: Ninety patients who had been treated by furosemide at routine dose for 12 hour but with unsatisfactory outcomes were selected and subjected to continuous intravenous infusion with high-dose furosemide. The dose was adjusted according to hourly urine output. Serum levels of urea nitrogen, creatinine and potassium, pH, oxygenation index and mechanical ventilation time before and 6, 12, 24, 48 and 72 hour after treatment were compared. Results: The urine outputs before and 6, 12, 24, 48 and 72 hour after treatment were (10.71±1.81), (164.52±21.42), (189.71±29.61), (181.33±23.52), (176.82±24.80) and (164.52±18.91) ml/h respectively. Compared with data before treatment, the serum levels of urea nitrogen, creatinine and potassium significantly decreased while pH and oxygenation index significantly increased after six hour of treatment (P<0.05). After treatment, the kidney functions of 80 patients (88.9%) were completely recovered, without obvious adverse reactions. Conclusion: For patients with early AKI complicated with acute pulmonary edema who cannot be cured by diuretic agent at routine dose, high-dose furosemide increases urine output and improves success rate. doi: https://doi.org/10.12669/pjms.35.3.1012 How to cite this:Ni J, Jiang H, Wang F, Zhang L, Sha D, Wang J. Effect of continuous furosemide infusion on outcome of acute kidney injury. Pak J Med Sci. 2019;35(3):---------. doi: https://doi.org/10.12669/pjms.35.3.1012 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2013 ◽  
Vol 119 (5) ◽  
pp. 1228-1232 ◽  
Author(s):  
Jingsong Zeng ◽  
Wusong Tong ◽  
Ping Zheng

Object The authors undertook this study to evaluate the effects of continuous intracranial pressure (ICP) monitoring–directed mannitol treatment on kidney function in patients with moderate or severe traumatic brain injury (TBI). Methods One hundred sixty-eight patients with TBI were prospectively assigned to an ICP monitoring group or a conventional treatment control group based on the Brain Trauma Foundation guidelines. Clinical data included the dynamic changes of patients' blood concentrations of cystatin C, creatinine (Cr), and blood urea nitrogen (BUN); mannitol use; and 6-month Glasgow Outcome Scale (GOS) scores. Results There were no statistically significant differences with respect to hospitalized injury, age, or sex distribution between the 2 groups. The incidence of acute kidney injury (AKI) was higher in the control group than in the ICP monitoring group (p < 0.05). The mean mannitol dosage in the ICP monitoring group (443 ± 133 g) was significantly lower than in the control group (820 ± 412 g) (p < 0.01), and the period of mannitol use in the ICP monitoring group (3 ± 3.8 days) was significantly shorter than in the control group (7 ± 2.3 days) (p < 0.01). The 6-month GOS scores in the ICP monitoring group were significantly better than in the control group (p < 0.05). On the 7th, 14th, and 21st days after injury, the plasma cystatin C and Cr concentrations in the ICP-monitoring group were significantly higher than the control group (p < 0.05). Conclusions In patients with moderate and severe TBI, ICP-directed mannitol treatment demonstrated a beneficial effect on reducing the incidence of AKI compared with treatment directed by neurological signs and physiological indicators.


2018 ◽  
Vol 13 (4) ◽  
pp. 25-33
Author(s):  
O. I. Kit ◽  
E. M. Frantsiyants ◽  
D. A. Rozenko ◽  
N. D. Ushakova ◽  
S. N. Dimitriadi ◽  
...  

Objective: to investigate the time course of changes in the early biomarkers of acute kidney injury in patients with clinically localized cancer during partial nephrectomy, as electively indicated, under thermal ischemia with prior epidural block.Materials and methods. To analyze the nephroprotective effect of an epidural block in kidney resection with warm ischemia, markers of acute kidney injury (cystatin C, interleukin 18, NGAL, L-FABP and KIM-1) were studied by ELISA in the blood and urine of 35 patients with local cancer with an epidural block (main group) and 37 patients with local cancer without an epidural block (control group) before surgery and 40 min after its beginning and on days 1 and 3 of the postoperative period. All patients were divided into 2 groups by the levels of cystatin C in the blood serum: 1000 ng/ml and lower, and over 1000 ng/ml.Results. Epidural block during the perioperative period in kidney resection with warm ischemia for patients with local cancer had an obvious nephroprotective effect allowing maintaining the initial renal functional parameters, in contrast to the standard disease management.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Esmaeel Babaeenezhad ◽  
Forouzan Hadipour Moradi ◽  
Sobhan Rahimi Monfared ◽  
Mohammad Davood Fattahi ◽  
Maryam Nasri ◽  
...  

Clinical application of gentamicin (GM) is well known to be associated with the development of acute kidney injury (AKI). This study was the first to investigate the possible protective effects of D-limonene (D-lim) on AKI following GM administration in rats. 32 rats arranged in four groups ( n = 8 ): (1) the control group received saline intraperitoneally (0.5 ml/day) and orally (0.5 ml/day), (2) the D-lim group received D-lim (100 mg/kg) orally and saline (0.5 ml/day) intraperitoneally, (3) the GM group received GM (100 mg/kg/day) intraperitoneally and saline (0.5 ml/day) orally, and (4) the treated group received intraperitoneal GM (100 mg/kg) and oral D-lim (100 mg/kg). All treatments were performed daily for 12 consecutive days. Results revealed that D-lim ameliorated GM-induced AKI, oxidative stress, mitochondrial apoptosis, and inflammation. D-lim showed nephroprotective effects as reflected by the decrease in serum urea and creatinine and improvement of renal histopathological changes. D-lim alleviated GM-induced oxidative stress by increasing the activities of renal catalase, serum and renal glutathione peroxidase, and renal superoxide dismutase and decreasing renal malondialdehyde and serum nitric oxide levels. Intriguingly, D-lim suppressed mitochondrial apoptosis by considerably downregulating Bax and caspase-3 (Casp-3) mRNA and protein expressions and markedly enhancing Bcl2 mRNA and protein expressions. Furthermore, D-lim significantly decreases GM-induced inflammatory response through downregulation of NF-κB, IL-6, and TNF-α mRNA and/or protein expressions and decrease in renal myeloperoxidase activity. Finally, D-lim remarkably downregulated PCNA protein expression in the treated group compared with the GM group. In brief, this study showed that D-lim alleviated AKI following GM administration in rats, partially through its antioxidant, anti-inflammatory, and antiapoptotic activities as well as downregulation of PCNA expression.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Jufitriani Ismy ◽  
Maimun Syukri ◽  
Dessy R. Emril ◽  
Nanan Sekarwana ◽  
Jufriady Ismy ◽  
...  

Sepsis is one of the leading causes contributing to the incidence of acute kidney injury (AKI). Oxidative stress can be used as the main approach against sepsis-induced AKI. One of the primary antioxidants that plays a role in warding off oxidative stress is superoxide dismutase (SOD). This research aimed to observe the effect of antioxidant SOD in inhibiting sepsis in AKI based on kidney tissue histopathology. The research method was an experimental laboratory with a post-test-only control group design. Twenty-five adult male rats aged 12–16 weeks, weighing between 200 and 250 g, were randomly divided into five groups: Group I, as a positive control, where rats were injected with lipopolysaccharides (LPS); Group II, as a negative control; Group III, as treatment 1, where rats were injected with LPS and administered orally with SOD (Glisodin®) 250 IU daily; Group IV, as treatment 2, where rats were injected with LPS and administered orally with SOD (Glisodin®) 500 IU daily; and Group V, as treatment 2, where rats were injected with LPS and administered orally with SOD (Glisodin®) 1000 IU daily. Rats were administered with SOD (Glisodin®) by oral gavage with a flexible feeding tube for 16 weeks, given once daily in the morning, and then injected with LPS of 10 mg/kg body weight. Glisodin SOD had a significant effect on murine sepsis score (MSS). MSS influenced the tubular injury score linearly. We conclude that the optimal dose of SOD at 1000 IU for inhibiting sepsis-induced AKI incidence is compared to SOD at a dose of 250 and 500 IU. The antioxidant effect of SOD can prevent sepsis-induced AKI with oxidative stress events.


2021 ◽  
Author(s):  
Yuanyuan Pei ◽  
Guangping Zhou ◽  
Pengfei Wang ◽  
Fang'e Shi ◽  
Xiaolu Ma ◽  
...  

Abstract Background: Acute kidney injury (AKI) was a common and critical complication of sepsis, and is associated with unacceptable morbidity and mortality. Current diagnostic criteria for AKI was insensitive for early detection. Novel biomarkers included cystatin C, KIM-1, NGAL, klotho and FGF-23 which can predict AKI earlier may allow immediate interventions. We aimed to determine the diagnostic performance of these biomarkers for detecting AKI in sepsis patients.Methods: This prospective observational study was conducted from May 2018 and November 2020, enrolling sequential 162 sepsis patients. AKI’s definition was according to 2012 KDIGO criteria and we divided patients into non-AKI (n=102) and AKI (n=60) groups. Serum levels of several AKI biomarkers were detected by ELISA. The relationship between biomarker levels on admission of AKI were analyzed and discrimination performances comparison were performed.Results: AKI incidence was up to 37.0% (60/162) during hospitalization. Compared with non-AKI group, both serum cystatin C, KIM-1, NGAL and FGF-23 were significantly elevated at admission in septic AKI patients. The areas under the receiver operating curves demonstrated that serum cystatin C had modest discriminative powers for predicting AKI after sepsis, and cystatin C combined with serum creatinine in the prediction of septic AKI increased the diagnostic sensitivity prominently.Conclusion: Serum cystatin C, KIM-1, NGAL and FGF-23 levels are both increased in septic AKI patients. Our study provides reliable evidence that cystatin C solely and combined with serum creatinine may accurately and sensitively predict septic AKI when patients on admission.


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 ◽  
...  

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


2021 ◽  
Vol 8 ◽  
Author(s):  
Hai-Ping Xu ◽  
Xiao-Ying Ma ◽  
Chen Yang

Sepsis is an inflammatory disorder and leads to severe acute kidney injury (AKI). Circular RNAs (circRNAs) have been identified as a critical type of regulatory noncoding RNAs (ncRNAs) that present the important functions in various diseases. In this study, we identified a novel circRNA circTLK1 in the regulation of sepsis-induced AKI. We observed that circTLK1 expression was elevated in the cecal ligation and puncture (CLP) rat model compared with that in the control rats. The urine levels of neutrophil gelatinase–associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) and the serum levels of creatinine (sCr) and blood urea nitrogen (BUN) were increased by the CLP treatment in the rats but were blocked by the circTLK1 shRNA. The circTLK1 shRNA reduced the CLP-induced kidney injury in the rats. The circTLK1 knockdown repressed oxidation stress, inflammation, and apoptosis in the sepsis-related AKI rat model. Moreover, lipopolysaccharide (LPS) treatment increased the production of TNF-α, IL-1β, and IL-6 in the HK-2 cells, while the circTLK1 shRNA could attenuate the enhancement in the cells. Bax and cleaved caspase-3 expression was upregulated, but Bcl-2 expression was downregulated by the LPS in the HK-2 cells, in which circTLK1 depletion reversed this effect in the cells. The depletion of circTLK1 attenuated the LPS-induced apoptosis in the HK-2 cells. CircTLK1 enhanced HMGB1 expression by sponging miR-106a-5p in the HK-2 cells, and miR-106a-5p and HMGB1 were involved in circTLK1-meidated injury of LPS-treated cells. Therefore, we concluded that circTLK1 contributed to sepsis-associated AKI by regulating inflammation and oxidative stress through the miR-106a-5p/HMGB1 axis. CircTLK1 and miR-106a-5p may be employed as the potential targets for the treatment of AKI.


Sign in / Sign up

Export Citation Format

Share Document