Nuclear factor kappa B in urine sediment: a useful indicator to detect acute kidney injury in Plasmodium falciparum malaria

Introduction: Acute kidney injury is a widespread complication in hospitalized patients, with a high mortality rate and long-term complications affecting prognosis and quality of life and with high human and financial costs. In addition, to date, no clear algorithm for the prevention of this type of damage has been developed. Materials and methods: The research was carried out on male Wistar rats. A 40-minute renal ischemia-reperfusion model was used to model acute kidney injury. Further, the renoprotective properties of carbamylated darbepoetin, udenafil and their combination were assessed based on the analysis of the biochemical studies’ results, dynamics of the renal status and the renal microvasculature, and the pathomorphological picture. A series of experiments was also carried out to assess the contribution of adenosine triphosphate-dependent potassium channels and nuclear factor kappa B to the renoprotective properties of the said agents. Results and discussion: Prophylactic administration of carbamylated darbepoetin at a dose of 50 µg/kg and udenafil at a dose of 8.7 mg/kg led to a statistically significant decrease in creatinine and blood urea nitrogen, an increase in glomerular filtration rate with a simultaneous decrease in fractional excretion of sodium, as well as an increase in the level of microcirculation in the kidneys and a decrease in the severity of damage according to the data of a pathomorphological examination at all time points of the experiment. A higher efficiency of correcting ischemic and reperfusion renal injuries was observed when using a combination of the said pharmacological agents. A series of experiments with glibenclamide demonstrated that its preliminary administration levels the renoprotective properties of carbamylated darbepoetin and udenafil. The ability of the studied pharmacological agents to reduce lipopolysaccharide-induced expression of nuclear factor kappa B in mononuclear cells was also demonstrated. The results of the research suggest that the renoprotective effects of carbamylated darbepoetin, udenafil, and their combination are realized through ATP-dependent potassium channels and nuclear factor kappa B. Conclusion: Pharmacological preconditioning with carbamylated darbepoetin and udenafil reduces the severity of acute kidney injury induced by ischemia-reperfusion. Graphical abstract:

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Acute Kidney Injury in Children with Plasmodium Falciparum Malaria: Determinants for Mortality

Peritoneal Dialysis International ◽

10.3747/pdi.2014.00254 ◽

2016 ◽

Vol 36 (2) ◽

pp. 213-217 ◽

Cited By ~ 7

Author(s):

Rajniti Prasad ◽

Om P. Mishra

Keyword(s):

Acute Kidney Injury ◽

Falciparum Malaria ◽

Disseminated Intravascular Coagulation ◽

Renal Involvement ◽

Kidney Injury ◽

Plasmodium Falciparum Malaria ◽

Peripheral Blood Smear ◽

Systemic Complications ◽

Intravascular Coagulation ◽

Duration Of Illness

Background Acute kidney injury (AKI) in P. falciparum malaria infection is an important morbidity in children. The purpose of the present study was done to observe the renal involvement, associated morbidities and outcome. Methods Out of 156 patients with severe P. falciparum malaria, diagnosed on the basis of compatible clinical presentations and positive malarial parasites in the peripheral blood smear and/or histidine rich protein 2 antigen, 31 had AKI at presentation and were analyzed. Results Of 31 (19.9%) patients with AKI, 4 were classified at risk, 11 injury, and 16 failure stage, as per pRIFLE criteria (pediatric version of RIFLE [R = risk, I = injury, F = failure, L = loss E = end-stage kidney disease]). Mean age of children with AKI was 7.7 ± 3.2 years. A significantly higher proportion of patients with AKI had hypoglycemia (41.9%), pulmonary edema (32.2%), and disseminated intravascular coagulation (DIC) (29.0%) compared to those without AKI (18.4%, 4.8%, and 3.2%, respectively). Twelve patients (38.7%) required peritoneal dialysis (PD), 8 (25.8%) died, and all were in failure stage. The non-survivors had significantly higher blood urea ( p = 0.005) and serum creatinine levels ( p = 0.042), lower glomerular filtration rate ( p < 0.001), longer duration of illness ( p = 0.003), and oliguria/anuria ( p = 0.001) than survivors at admission. On logistic regression analysis, the disseminated intravascular coagulation (DIC), jaundice and parasite density (≥ 3+) were found to be significant factors contributing to mortality in children with AKI. Conclusions Acute kidney injury in falciparum malaria is one of the severe systemic complications. Duration of illness and presence of comorbidities adversely affected the outcome.

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Sanguinarine Ameliorates Diabetic Nephropathy in Rats through Nuclear Factor-Kappa B and Nuclear-Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathways

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:398-404 ◽

2021 ◽

Vol 19 (4) ◽

pp. 398-404

Author(s):

Jiao Zhong

Keyword(s):

Diabetic Nephropathy ◽

Heme Oxygenase ◽

Nuclear Factor Kappa B ◽

Kidney Injury ◽

Diabetic Rats ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Related Complication ◽

Nuclear Factor Kappa

Alkaloids - derived from natural plants - were widely used for therapy in diabetes or diabetes-related complications. Sanguinarine, a benzophenanthridine alkaloid derived from Sanguinaria canadensis, has been identified as a potential drug for type 2 diabetes. However, the role of sanguinarine on diabetes-related complication, diabetic nephropathy, has not been reported yet. In a rat model of diabetic nephropathy we have demonstrated increased levels of 24 h urinary proteins, serum creatinine, and blood urea nitrogen, as well as series of degenerative changes in the kidney tissues. Oral administration with sanguinarine to diabetic rats diminished kidney injury markers and improved the tissue morphology. Furthermore, sanguinarine attenuated increase in the levels of tumor necrosis factor-α and interleukin-6 through downregulation of phosphonuclear factor-kappa B and phosphorylated inhibitor of nuclear factor kappa-B. Lastly, sanguinarine reversed the effects of streptozotocin on levels of reactive oxygen species, malonaldehyde, superoxide dismutase, and glutathione peroxidase through upregulation of nuclear factor erythropoietin-2-related factor 2, heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 in kidney of rats. In conclusion, sanguinarine ameliorates diabetic nephropathy in rats through inactivation of nuclear factor-kappa B and activation of nuclear-factor erythroid 2-related factor 2 pathways.

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P0174NEPHROPROTECTIVE ACTIVITY OF GOSSYPETIN THROUGH INHIBITORY EFFECT ON XANTHINE OXIDASE, NUCLEAR FACTOR KAPPA B (NF-KB) AND SOLUBLE EPOXIDE HYDROLASE (SEH): IN-VITRO AND IN-SILICO EXPERIMENT

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0174 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Dinesh Kumar Patel ◽

Kanika Patel

Keyword(s):

Uric Acid ◽

In Silico ◽

Epoxide Hydrolase ◽

Nuclear Factor Kappa B ◽

Kidney Injury ◽

Soluble Epoxide Hydrolase ◽

Inflammatory Activity ◽

Nuclear Factor ◽

Nuclear Factor Kappa ◽

Anti Inflammatory

Abstract Background and Aims Oxidative stress and inflammation is the major contributor of kidney injury and the drugs which have antioxidant and anti-inflammatory activity could protect kidney against renal damage. Mechanisms involved in renal failure include oxidative stress, inflammation and apoptosis which lead myoglobinemia, myoglobinuria and cast formation. Inflammatory mediators such as IL-1, ICAM-1 and TNFα also play important role in renal failure. Excess production of uric acid can cause serious consequence in hyperuricemia and xanthine oxidase (XO) catalyzes the oxidation of xanthine to uric acid. Protective effects of gossypetin in the management of kidney injury and related disorders have been investigated in the present work through inhibitory potential of gossypetin on nuclear factor kappa B (NF-κB), soluble epoxide hydrolase (sEH) and XO. Method Present work described the medicinal importance of gossypetin with their beneficial effect on kidney disorder. In-silico molecular docking and dynamic experiments were carried out with gossypetin against nuclear factor kappa B (NF-κB) and soluble epoxide hydrolase (sEH). Further docking was also performed to investigate how gossypetin and the active site of XO fit together. Results From the analysis of the available data’s in the present work, it was found that gossypetin have protective effect against nephrotoxicity. Gossypetin also showed potent anti-inflammatory activity in kidney mesangial cells which further support application of natural compounds on nephritis treatment. Importance of gossypetin for preventing renal damage has been also emphasized due to its antioxidants potential. In-silico studies showed that, gossypetin exhibited a higher docking score against NF-κB and sEH. Docking studies revealed gossypetin surrounds the active sites of XO and reduces conversion of xanthine to uric acid. Conclusion Study revealed their antioxidant, anti-mutagenic, anti-atherosclerotic, anti-microbial and cytoprotective properties. The protective effect of gossypetin in kidney could be due to its antioxidant and anti-inﬂammatory activity through inhibition of NF-κB and sEH upregulation.

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