Protective Effect of Calcium Dobesilate on Induced AKI in Severely Burned Mice

Nephron ◽  
2021 ◽  
pp. 1-15
Author(s):  
Nazma Akhter ◽  
Hong Sun ◽  
Jerrmia Ong’achwa Machuki ◽  
Hong-qi Ren
Keyword(s):  
Protein Kinase ◽  
Protective Effect ◽  
Total Body Surface Area ◽  
Reactive Oxygen Species Generation ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Tubular Damage ◽  
Severe Burn ◽  
Calcium Dobesilate ◽  
Renal Histology

<b><i>Background:</i></b> Early acute kidney injury (AKI) predicts a high mortality rate in severely burned patients. However, the pathophysiology of early AKI induced by severe burn has not been well-defined. This study was designed to examine the protective effects of calcium dobesilate (CaD) against severe burn-induced early AKI in mice and explore the mechanism. <b><i>Methods:</i></b> The shaved backs of mice were immersed in 100°C water for 10 s to make severe burn (40% of the total body surface area). CD-57 male mice were randomly divided into sham, burn, burn + vehicle, and burn + CaD groups. Renal function, reactive oxygen species generation, tubular necrosis, and phosphorylation of mitogen-activated protein kinase, protein kinase B (Akt), and nuclear factor (NF)-κB were measured at 24 and 48 h after the burn. Renal histology, ELISA, qRT-PCR, and Western blotting were performed on the renal tissue of mice to examine the effects and mechanisms at 24 and 48 h after the burn. <b><i>Results:</i></b> Tubular damage, cast formation, and elevations of serum creatinine, BUN, and renal tissue kidney injury molecule 1 levels were all observed in the burned mice, and these were all alleviated in the mice with CaD treatment. In addition, the levels of oxidation-reduction potential and malondialdehyde were decreased, while the activities of the endogenous antioxidative enzymes were increased in the kidney tissues from the mice after CaD treatment. Furthermore, the activities of Akt, p38, extracellular sign-regulated kinase, Jun N-terminal kinase, and NF-κB signaling were increased in the kidney of burned mice and normalized after CaD treatment. <b><i>Conclusion:</i></b> This study has established, for the first time, the protective effect of CaD against early AKI in severely burned mice. CaD may exert its protective effect through alleviating oxidative stress, apoptosis, and inflammation, as well as modulating some signaling pathways in the kidney.

Protective Effect of Calcium Dobesilate Administration Against Hepatorenal Damage Induced By CCL4 In Male Mice

2021 ◽  
Author(s):  
Elham Hakimizadeh ◽  
Ayat Kaeidi ◽  
Mohammadreza Rahmani ◽  
Mohammad Allahtavakoli ◽  
Jalal Hassanshahi
Keyword(s):  
Protective Effect ◽  
Antioxidant Properties ◽  
Group Versus ◽  
Histopathological Change ◽  
Renal Tissue ◽  
Protective Effects ◽  
Male Mice ◽  
Calcium Dobesilate ◽  
Liver And Kidney ◽  
Anti Inflammatory

Abstract Purpose: Calcium dobesilate (CaD) has antioxidant and anti-inflammatory properties. In this study, the protective effects of CaD against hepatorenal damage induced by CCL4 in male mice were evaluated. Methods: Thirty male mice randomly were divided into five groups: Control, CaD 100 mg/kg, CCL4, CCL4+CaD 50 mg/kg, and CCL4+CaD 100 mg/kg. Drugs were administered orally once a day for 4-weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase and aspartate aminotransferase levels) were determined. Also, hepatic and renal tissue oxidant/antioxidant markers (glutathione peroxidase, malondialdehyde, total antioxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, and Bcl-2 protein levels were measured by immunoblotting method. The liver and kidney histopathological changes were evaluated by H&E staining.Results: CCL4 induces significant oxidative stress in the kidney and liver that was concomitant with functional and histopathological abnormalities in these organs in the CCL4 group versus the control (P<0.05). CaD could significantly improve the histopathological change in the liver and kidney tissues of CCL4+CaD 100 mg/kg mice versus the CCL4 group (P<0.05). In addition, CaD attenuated apoptosis in the liver and kidney tissues (P<0.05).Conclusion: The protective effect of CaD may be related to its anti-inflammatory and antioxidant properties.

Platycodin D Ameliorates Acute Kidney Injury in Septic Rats by Regulating Mitogen Activated Protein Kinase Pathway

2020 ◽  
Vol 19 (3) ◽  
pp. 270-276
Author(s):  
Jianying Wang ◽  
Xiaoting Yu
Keyword(s):  
Acute Kidney Injury ◽  
Protein Kinase ◽  
Protective Effect ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
B Cell Lymphoma ◽  
Mitogen Activated Protein Kinase ◽  
Cecal Ligation And Puncture ◽  
Platycodin D ◽  
Mitogen Activated Protein

Acute kidney injury is a severe complication of sepsis. We have shown a protective effect of Platycodin D on sepsis induced acute kidney injury in an animal model that employs cecal ligation and puncture. Cecal ligation and puncture induced a series of degenerative changes in kidney, such as edema, hyperemia, and expansion in glomerular capillary, and inflammatory cells infiltration that were attenuated by Platycodin D. Also, rise in proinflammatory cytokine levels in septic rats was blunted by Platycodin D. Furthermore, Platycodin D administration reduced rise in serum levels of kidney injury markers-blood urea nitrogen and serum creatinine-in septic rats. Moreover, Platycodin D administration also suppressed the cell apoptosis in kidney that was associated with enhanced B-cell lymphoma 2 protein and reduced cleaved cysteine-aspartic protease-3 and BCL2-associated X protein. Lastly, Platycodin D administration attenuated sepsis-induced increase of phospho (p)-extracellular signal-regulated kinase, p-c-Jun NH2-terminal kinase, and p-p38. In conclusion, Platycodin D demonstrated protective effect against sepsis induced acute kidney injury through inactivation of mitogen activated protein kinase pathways, thus providing promising therapeutic strategy for the treatment of sepsis.

scholarly journals ADAMTS-13-Regulated Nrf2 Signaling Inhibits Ferroptosis to Ameliorate Cisplatin-Induced Acute Kidney Injury

2021 ◽  
Author(s):  
Xiaoyan Meng ◽  
Wenjing Huang ◽  
Weiwei Mo ◽  
Tingting Shu ◽  
Haoqiang Yang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Western Blot ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Tubular Damage ◽  
Nrf2 Signaling Pathway ◽  
Function Impairment ◽  
Pas Staining ◽  
Related Proteins ◽  
The Relationship

Abstract Background: ADAMTS-13 plays an important role in acute kidney injury (AKI), but the mechanism of cisplatin (CP) induced AKI remains unclear. Ferroptosis is increased in CP-induced AKI, and ADAMTS13 levels are associated with ferritin expression. In this article, we will explore the relationship between the three.Methods： After CP induction, mice were given 0.1 and 0.3nmol/kg ADAMTS-13, and then Scr and BUN were detected by the kits. The pathological changes of renal tissue were observed by staining with HE and PAS staining, and Western blot detected the expressions of KIM1 and NGAL in renal tissu. Perl's staining detected iron deposition in renal tissues, the kits detected iron levels, and western blot detected the expression of ferroptosis related proteins. Then the mechanism was further explored by adding ferroptosis inhibitors Ferrostatin 1 (Fer-1) and iron supplements Fe. The expression of Nrf2 pathway related proteins were detected by Western blot.Results: ADAMTS13 alleviated CP-induced ferroptosis in AKI mice with renal function impairment and tubular damage. Fer-1partially reversed CP-induced AKI, and Fe exacerbated this effect. ADAMTS13 alleviated CP-induced inflammatory response and oxidative stress in AKI mice, during which the Nrf2 signaling pathway was abnormal.Conclusion:ADAMTS-13-regulated Nrf2 signaling inhibits ferroptosis to ameliorate CP-induced AKI.

scholarly journals Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

2012 ◽  
Vol 302 (5) ◽  
pp. F561-F570 ◽  
Author(s):  
Yanzhang Li ◽  
Xiaopeng Tong ◽  
Hasiyeti Maimaitiyiming ◽  
Kate Clemons ◽  
Ji-Min Cao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Transgenic Mice ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

cGMP-dependent protein kinase (PKG) is a multifunctional protein. Whether PKG plays a role in ischemia-reperfusion-induced kidney injury (IRI) is unknown. In this study, using an in vivo mouse model of renal IRI, we determined the effect of renal IRI on kidney PKG-I levels and also evaluated whether overexpression of PKG-I attenuates renal IRI. Our studies demonstrated that PKG-I levels (mRNA and protein) were significantly decreased in the kidney from mice undergoing renal IRI. Moreover, PKG-I transgenic mice had less renal IRI, showing improved renal function and less tubular damage compared with their wild-type littermates. Transgenic mice in the renal IRI group had decreased tubular cell apoptosis accompanied by decreased caspase 3 levels/activity and increased Bcl-2 and Bag-1 levels. In addition, transgenic mice undergoing renal IRI demonstrated reduced macrophage infiltration into the kidney and reduced production of inflammatory cytokines. In vitro studies showed that peritoneal macrophages isolated from transgenic mice had decreased migration compared with control macrophages. Taken together, these results suggest that PKG-I protects against renal IRI, at least in part through inhibiting inflammatory cell infiltration into the kidney, reducing kidney inflammation, and inhibiting tubular cell apoptosis.

scholarly journals Artificial Intelligence Imaging to Observe the Protective Effect of Hydrogen Sulfide on Acute Kidney Injury Caused by Urinary Sepsis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ziying Yu ◽  
Xiaoli Zhang
Keyword(s):  
Artificial Intelligence ◽  
Acute Kidney Injury ◽  
Hydrogen Sulfide ◽  
Protective Effect ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Diagnosis And Treatment ◽  
Sepsis Group ◽  
Short Period ◽  
Urinary Sepsis

With the development of medical technology products and the rapid development of computer technology, medical AI has become a hotbed in scientific research and clinical practice. Some medical AI-assisted diagnosis has been applied to the clinic to assist doctors in formulating treatment plans. The traditional method of clinical diagnosis and treatment is that the physician makes an intentional diagnosis and then performs ancillary tests. The clinician performs diagnosis and treatment by identifying clinical symptoms and analyzing auxiliary examination results. Modern medical AI is based on big data collection and analyzes the test results through artificial intelligence and computer algorithms. It can output diagnostic results with high sensitivity and specificity for clinical tests. Acute kidney injury (AKI) is a common clinical emergency. The main clinical features are elevated blood creatinine, decreased urine output, and sharp decline in renal function within a short period of time, and it is a hot spot worldwide. In this experiment, a rabbit sepsis model was replicated by inoculating E. coli bacteria into the rabbit’s unilateral ureteral lumen and ligation. NaHS was used as an exogenous hydrogen sulfide donor to observe the effects of hydrogen sulfide on UTIs. The protective effect of oxidative stress and inflammatory response in acute kidney injury with hyperemia. In the experiment, the production of endogenous hydrogen sulfide was decreased in the Sepsis group, and the renal CSE activity was decreased, while the content of endogenous hydrogen sulfide in the NaHS group was higher than that of the Sepsis group, and the CSE activity of renal tissue was increased. It can be seen that the plasma hydrogen sulfide and renal tissue SCE levels in septic acute kidney injury increased after NaHS intervention, and the renal tissue damage was reduced, suggesting that hydrogen sulfide is mainly generated endogenously through the action of CSE, which causes damage to the kidneys. The expressions of iNOS and HO-1 in renal tissues of urinary sepsis are increased. H2S can play a certain protective effect on acute kidney injury in urinary sepsis by down-regulating iNOS and up-regulating the expression of HO-1.

Roflumilast, a phosphodiesterase 4 inhibitor, attenuates cadmium-induced renal toxicity via modulation of NF-κB activation and induction of NQO1 in rats

2019 ◽  
Vol 38 (5) ◽  
pp. 588-597 ◽  
Author(s):  
MN Ansari ◽  
RI Aloliet ◽  
MA Ganaie ◽  
TH Khan ◽  
Najeeb-ur-Rehman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Urine Volume ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Treated Group ◽  
Renal Tissue ◽  
High Dose ◽  
Dependent Manner ◽  
Histopathological Studies

Objective: In the present study, the protective effect of Roflumilast (ROF, a selective phosphodiesterase (PDE-4) inhibitor) was investigated against cadmium (Cd)-induced nephrotoxicity in rats. Methods: A total of 24 rats were selected and randomly divided into four groups ( n = 6). Group 1 served as the control; groups 2–4 administered with CdCl2 (3 mg/kg, i.p.) for 7 days; groups 3 and 4 were co-administered with ROF in doses of 0.5 and 1.5 mg/kg, orally for 7 consecutive days. Nephrotoxicity was evaluated by measuring urine volume, urea and creatinine levels in urine and serum. Oxidative stress was confirmed by measuring malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels in kidney tissue followed by histopathological studies. Results: CdCl2 administration results in a significant ( p < 0.01) decrease in urine volume, urea, and creatinine levels in urine, as well as GSH, SOD, and CAT levels in renal tissue. In addition, Cd also produced significantly increased ( p < 0.01) urea and creatinine levels in serum and TBARS levels in renal tissues. Rats treated with ROF significantly ( p < 0.01) restore the altered levels of kidney injury markers, nonenzymatic antioxidant, as well as depleted enzymes in dose-dependent manner. An increased expression of NF-κB p65 and decreased expression of GST and NQO1 in the Cd only treated group were significantly reversed by high dose of ROF (1.5 mg/kg). Histopathological changes were also ameliorated by ROF administration in Cd-treated groups. Conclusion: In conclusion, ROF treatment showed protective effect against renal damage and increased oxidative stress induced by Cd administration.

scholarly journals Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Marco A. C. de Resende ◽  
Alberto V. Pantoja ◽  
Bruno M. Barcellos ◽  
Eduardo P. Reis ◽  
Thays D. Consolo ◽  
...  
Keyword(s):  
Renal Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Arterial Occlusion ◽  
Kidney Injury ◽  
Ischemic Postconditioning ◽  
Tubular Damage ◽  
Ketamine Infusion ◽  
Renal Histology

Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI.Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology.Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG.Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model.

scholarly journals Protective Effect of Joa-Gui Em through the Improvement of the NLRP3 and TLR4/NF-κb Signaling by Ischemia/Reperfusion-Induced Acute Renal Failure Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Se Won Na ◽  
Youn Jae Jang ◽  
Mi Hyeon Hong ◽  
Jung Joo Yoon ◽  
Ho Sub Lee ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Protective Effect ◽  
Kidney Function ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Kidney Size ◽  
Acute Renal Dysfunction

Joa-gui em (左歸飮, JGE) is known to be effective for treating kidney-yin deficient syndrome. However, there is a lack of objective pharmacological research on improving kidney function. This study was designed to evaluate whether JGE improves renal function and related mechanisms in rats with acute renal injury induced by ischemia/reperfusion (I/R). The acute renal failure (ARF) group was subjected to reperfusion after inserting a clip into the renal artery for 45 min. The ARF + JGE (100 or 200 mg/kg/day) groups were orally administered for four days after their I/R surgery, respectively. JGE treatment suppressed the increase in kidney size in the ARF animal model and alleviated the polyuria symptoms. In addition, to confirm the effect of improving the kidney function of JGE, lactate dehydrogenase levels, blood urea nitrogen/creatinine ratio, and creatinine clearance were measured. As a result, it decreased in the ARF group but significantly improved in the JGE group. Also, as a result of examining the morphological aspects of renal tissue, it was shown that JGE improved renal fibrosis caused by ARF. Meanwhile, it was confirmed that JGE reduced inflammation through the nucleotide-binding oligomerization domain-like receptor pyrin domain containing-3 (NLRP3) and toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathways, which are the major causes of acute ischemic kidney injury, thereby improving renal function disorder. The JGE has a protective effect by improving the NLRP3 and TLR4/NF-κB signaling pathway in rats with acute renal dysfunction induced by I/R injury.

Evaluating the Proposed Mechanism by Which Atorvastatin Can Protect Renal Tissue against Contrast Media: An Animal study

2019 ◽  
pp. 75-84
Keyword(s):  
Contrast Media ◽  
Kidney Injury ◽  
Saline Group ◽  
Pleiotropic Effect ◽  
Renal Tissue ◽  
Male Rats ◽  
Dependent Manner ◽  
Group 2 ◽  
Dose Dependent ◽  
Media Group

Contrast- induced nephropathy (CIN) is an elevation of serum creatinine of ≥ 0.5 mg/dL from baseline after two to three days of exposure to contrast substance if there is no other cause for acute kidney injury. Atorvastatin may protect normal kidney physiology from contrast- induced kidney injury by effects unrelated to hypolipidemia termed pleiotropic effect by decline of endothelin production, angiotensin system down regulation, and under expression of endothelial adhesion molecules. This study was conducted to assess the strategy by which atorvastatin can achieve protective effect for kidneys after exposure to contrast media in an animal model. A 40 male rats were distributed randomly into 4 groups; ten rats for each: group (1): given normal saline; group (2): CIN group given iopromide as contrast media; group (3): given atorvastatin (20mg/kg) and iopromide; and group (4): given atorvastatin (40mg/kg) and iopromide. Blood collected by cardiac puncture for detection of serum glutathione, malondialdehyde, matrix metalloproteinase-9, and interleukin-18. The results have shown a significant increase in inflammatory and oxidative stress markers in contrast media group, and significant reduction in these markers in atorvastatin treated groups, in a dose-dependent manner. As conclusion, atorvastatin mechanism for protection against CIN in a dose-dependent manner can mediate by anti-inflammatory and antioxidant effects.

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