Exacerbates kidney injury in mice subjected to sepsis: critical impact of used heparin

2018 ◽  
Vol 6 (4) ◽  
pp. 323-335
Author(s):  
Peter Weighardt ◽  
Niels Hayashi
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Cytokine Production ◽  
Multiorgan Failure ◽  
Kidney Injury ◽  
Tubular Dysfunction ◽  
Cytokine Storm ◽  
Peritubular Capillary ◽  
Inflammatory Reactions ◽  
Local Cytokine

Sepsis is the leading cause of death in critically ill patients, and the incidence of sepsis is increasing causes multiorgan failure, including acute kidney injury (AKI) and patients with both sepsis and AKI have an especially high mortality rate. Several different pathophysiological mechanisms have been proposed for sepsis-induced AKI: vasodilation-induced glomerular hypoperfusion, dysregulated circulation within the peritubular capillary network, inflammatory reactions by systemic cytokine storm or local cytokine production, and tubular dysfunction induced by oxidative stress animal sepsis models have been developed using LPS infusion. Renal dysfunction evaluated by serum creatinine and BUN was found in acute non-survivors (<24 hours) and decreased urine output in subacute non-survivors (24–96 hours). The study show that increased AKI in animal with blood collected heparin (P=0.002) compared to citrate, furthermore; sham mice that received heparin did not develop AKI.

Exacerbates kidney injury in mice subjected to sepsis: critical impact of used heparin

2016 ◽  
Vol 4 (2) ◽  
pp. 203-216
Author(s):  
Peter Weighardt ◽  
Niels Hayashi
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Cytokine Production ◽  
Multiorgan Failure ◽  
Kidney Injury ◽  
Tubular Dysfunction ◽  
Cytokine Storm ◽  
Peritubular Capillary ◽  
Inflammatory Reactions ◽  
Local Cytokine

Sepsis is the leading cause of death in critically ill patients, and the incidence of sepsis is increasing causes multiorgan failure, including acute kidney injury (AKI) and patients with both sepsis and AKI have an especially high mortality rate. Several different pathophysiological mechanisms have been proposed for sepsis-induced AKI: vasodilation-induced glomerular hypoperfusion, dysregulated circulation within the peritubular capillary network, inflammatory reactions by systemic cytokine storm or local cytokine production, and tubular dysfunction induced by oxidative stress animal sepsis models have been developed using LPS infusion. Renal dysfunction evaluated by serum creatinine and BUN was found in acute non-survivors (<24 hours) and decreased urine output in subacute non-survivors (24–96 hours). The study show that increased AKI in animal with blood collected heparin (P=0.002) compared to citrate, furthermore; sham mice that received heparin did not develop AKI.

scholarly journals Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7589
Author(s):  
Jung-Yeon Kim ◽  
Hyo-Lim Hong ◽  
Gyun Moo Kim ◽  
Jaechan Leem ◽  
Hyun Hee Kwon
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Immune Cell ◽  
Multiorgan Failure ◽  
Kidney Injury ◽  
Nuclear Factor Κb ◽  
Medical Problem ◽  
Carnosic Acid ◽  
Protective Effects ◽  
Treatment Agent

Septic acute kidney injury (AKI) is an important medical problem worldwide, but current treatments are limited. During sepsis, lipopolysaccharide (LPS) activates various signaling pathways involved in multiorgan failure. Carnosic acid is a natural phenolic diterpene and has multiple bioactivities, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, the effect of carnosic acid on septic AKI has not been explored. Therefore, this study aimed to determine whether carnosic acid has a therapeutic effect on LPS-induced kidney injury. Administration of carnosic acid after LPS injection ameliorated histological abnormalities and renal dysfunction. Cytokine production, immune cell infiltration, and nuclear factor-κB activation after LPS injection were also alleviated by carnosic acid. The compound suppressed oxidative stress with the modulation of pro-oxidant and antioxidant enzymes. Tubular cell apoptosis and caspase-3 activation were also inhibited by carnosic acid. These data suggest that carnosic acid ameliorates LPS-induced AKI via inhibition of inflammation, oxidative stress, and apoptosis and could serve as a useful treatment agent for septic AKI.

scholarly journals Development of Oxidative Stress in the Peritubular Capillary Microenvironment Mediates Sepsis-Induced Renal Microcirculatory Failure and Acute Kidney Injury

2012 ◽  
Vol 180 (2) ◽  
pp. 505-516 ◽  
Author(s):  
Zhen Wang ◽  
Joseph H. Holthoff ◽  
Kathryn A. Seely ◽  
Elina Pathak ◽  
Horace J. Spencer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Peritubular Capillary

scholarly journals Vinpocetine reduces diclofenac-induced acute kidney injury through inhibition of oxidative stress, apoptosis, cytokine production, and NF-κB activation in mice

2017 ◽  
Vol 120 ◽  
pp. 10-22 ◽  
Author(s):  
Victor Fattori ◽  
Sergio M. Borghi ◽  
Carla F.S. Guazelli ◽  
Andressa C. Giroldo ◽  
Jefferson Crespigio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Cytokine Production ◽  
Kidney Injury

Serial Quantification of Urinary Protein Biomarkers to Predict Drug-induced Acute Kidney Injury

2019 ◽  
Vol 20 (8) ◽  
pp. 656-664 ◽  
Author(s):  
Yi Da ◽  
K. Akalya ◽  
Tanusya Murali ◽  
Anantharaman Vathsala ◽  
Chuen-Seng Tan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cystatin C ◽  
Calcineurin Inhibitors ◽  
Kidney Injury ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Protein Biomarkers ◽  
Drug Induced ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Background: : Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI. Methods:: We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine. Results:: Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p<0.05; their AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation. Conclusion: : Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.

scholarly journals Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 572
Author(s):  
Jung-Yeon Kim ◽  
Jungmin Jo ◽  
Jaechan Leem ◽  
Kwan-Kyu Park
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Renal Injury ◽  
Manganese Superoxide Dismutase ◽  
Immune Cell ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kidney Injury ◽  
Pleiotropic Effects ◽  
Induced Apoptosis ◽  
Vascular Adhesion

Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.

Long non-coding RNA SNHG14 aggravates LPS-induced acute kidney injury through regulating miR-495-3p/HIPK1

2021 ◽  
Author(s):  
Ni Yang ◽  
Hai Wang ◽  
Li Zhang ◽  
Junhua Lv ◽  
Zequn Niu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Kidney Injury ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Kidney Injury ◽  
Interaction Network ◽  
High Morbidity ◽  
Abrupt Decrease ◽  
Inflammatory Cytokine Production ◽  
Non Coding Rna

Abstract Acute kidney injury (AKI) is a complex syndrome with an abrupt decrease of kidney function, which is associated with high morbidity and mortality. Sepsis is the common cause of AKI. Mounting evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of sepsis-induced AKI. In this study, we aimed to illustrate the function and mechanism of lncRNA SNHG14 in lipopolysaccharide (LPS)-induced AKI. We found that SNHG14 was highly expressed in the plasma of sepsis patients with AKI. SNHG14 inhibited cell proliferation and autophagy and promoted cell apoptosis and inflammatory cytokine production in LPS-stimulated HK-2 cells. Functionally, SNHG14 acted as a competing endogenous RNA (ceRNA) to negatively regulate miR-495-3p expression in HK-2 cells. Furthermore, we identified that HIPK1 is a direct target of miR-495-3p in HK-2 cells. We also revealed that the SNHG14/miR-495-3p/HIPK1 interaction network regulated HK-2 cell proliferation, apoptosis, autophagy, and inflammatory cytokine production upon LPS stimulation. In addition, we demonstrated that the SNHG14/miR-495-3p/HIPK1 interaction network regulated the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β) via modulating NF-κB/p65 signaling in LPS-challenged HK-2 cells. In conclusion, our findings suggested a novel therapeutic axis of SNHG14/miR-495-3p/HIPK1 to treat sepsis-induced AKI.

scholarly journals Protective Effects of Carbon Dots Derived from Phellodendri Chinensis Cortex Carbonisata against Deinagkistrodon acutus Venom-Induced Acute Kidney Injury

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Meiling Zhang ◽  
Jinjun Cheng ◽  
Ziwei Sun ◽  
Hui Kong ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Carbon Dots ◽  
Biomedical Applications ◽  
Abdominal Cavity ◽  
Kidney Injury ◽  
Protective Effects ◽  
Inflammatory Reactions ◽  
Chemotactic Protein ◽  
Renal Histology ◽  
Deinagkistrodon Acutus

Abstract Background As an emerging nanomaterial, carbon dots (CDs) have been the focus of tremendous attention for biomedical applications. However, little information is available on their bioactivity of inhibiting acute kidney injury (AKI) induced by snake venom. Methods This study reports the development of a green, one-step pyrolysis process to synthesize CDs using Phellodendri Chinensis Cortex (PCC) as the sole precursor, and their potential application as a protectant against Deinagkistrodon acutus (D. acutus) venom-induced AKI was investigated for the first time. The AKI model was established by injecting D. acutus venom into the abdominal cavity of mice and the potential protective effects of PCC Carbonisata-CDs (PCCC-CDs) on renal abnormalities including dysfunction, inflammatory reactions, tissue damage, and thrombocytopenia at six time points (1, 3, and 12 h, and 1, 2, and 5 days) were investigated. Results These results demonstrated that PCCC-CDs significantly inhibited the kidney dysfunction (reduced serum creatinine (SCR), blood urea nitrogen (BUN), urinary total protein (UTP), and microalbuminuria (MALB) concentrations) and the production of chemoattractant (monocyte chemotactic protein 1 (MCP-1)), proinflammatory cytokines (interleukin (IL)-1β), and anti-inflammatory cytokine (IL-10) in response to intraperitoneal injection of D. acutus venom. The beneficial effect of PCCC-CDs on the envenomed mice was similar to that on the change in renal histology and thrombocytopenia. Conclusions These results demonstrated the remarkable protective effects of PCCC-CDs against AKI induced by D. acutus venom, which would not only broaden the biomedical applications of CDs but also provide a potential target for the development of new therapeutic drugs for AKI induced by D. acutus snakebite envenomation.

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