Browsing by Subject "Acute kidney injury"

Now showing 1 - 6 of 6
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    Aromadendrin alleviates LPS-induced kidney apoptosis and inflammation by inhibiting phosphorylation of MAPK and NF-κB signaling pathways
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Ma, Xiaohong; Liu, Wenhua; Wang, Bin; Shi, Feizhuang
    Background. Excessive inflammation and apoptosis in kidneys are critical players in the pathogenesis of acute kidney injury (AKI). Aromadendrin is a natural flavonoid characterized by anti-inflammatory, anti-apoptotic, and antioxidant actions. Thus, we investigated the roles and mechanisms of aromadendrin in the development of AKI. Methods. Lipopolysaccharide (LPS) was used to induce AKI mice, and one hour after LPS challenge, the mice received oral administration of aromadendrin or vehicle. Renal functions were assessed by measuring blood urea nitrogen and creatinine in serum. Histological changes were determined by hematoxylin and eosin staining. Apoptotic cells of renal tissues were detected by TUNEL staining. Gene expression was measured by western blotting and RT-qPCR. Results. Aromadendrin alleviated LPS-induced renal dysfunctions and histological defects in mice. Additionally, aromadendrin suppressed excessive inflammation and tissue apoptosis in the kidneys of LPS-induced AKI mice. Mechanistically, aromadendrin blocked the activation of NF-κB and MAPK pathways in LPS-induced AKI mice. Conclusion. Aromadendrin alleviates LPS-stimulated inflammation and tissue cell apoptosis in kidneys by inactivating the NF-κB and MAPK pathways
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    Automated systematic random sampling and Cavalieri stereology of histologic sections demonstrating acute tubular necrosis after cardiac arrest and cardiopulmonary resuscitation in the mouse
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Wakasaki, Rumie; Eiwaz, Mahaba; McClellan, Nicholas; Matsushita, Katsuyuki; Kirsti Golgotiu, Kirsti Golgotiu; Hutchens, Michael P.
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    Flavonoids in Kidney Health and Disease
    (Frontiers, 2018-04-24) Vargas, Félix; Romecín, Paola; Wangesteen, Rosemary; Atucha, Noemí M.; García-Estañ, Joaquín; García-Guillén, Ana I.; Vargas-Tendero, Pablo; Paredes, M. Dolores; Fisiología
    This review summarizes the latest advances in knowledge on the effects of flavonoids on renal function in health and disease. Flavonoids have antihypertensive, antidiabetic, and antiinflammatory effects, among other therapeutic activities. Many of them also exert renoprotective actions that may be of interest in diseases such as glomerulonephritis, diabetic nephropathy, and chemically-induced kidney insufficiency. They affect several renal factors that promote diuresis and natriuresis, which may contribute to their well-known antihypertensive effect. Flavonoids prevent or attenuate the renal injury associated with arterial hypertension, both by decreasing blood pressure and by acting directly on the renal parenchyma. These outcomes derive from their interference with multiple signaling pathways known to produce renal injury and are independent of their blood pressure-lowering effects. Oral administration of flavonoids prevents or ameliorates adverse effects on the kidney of elevated fructose consumption, high fat diet, and types I and 2 diabetes. These compounds attenuate the hyperglycemia-disrupted renal endothelial barrier function, urinary microalbumin excretion, and glomerular hyperfiltration that results from a reduction of podocyte injury, a determinant factor for albuminuria in diabetic nephropathy. Several flavonoids have shown renal protective effects against many nephrotoxic agents that frequently cause acute kidney injury (AKI) or chronic kidney disease (CKD), such as LPS, gentamycin, alcohol, nicotine, lead or cadmium. Flavonoids also improve cisplatin- or methotrexate-induced renal damage, demonstrating important actions in chemotherapy, anticancer and renoprotective effects. A beneficial prophylactic effect of flavonoids has been also observed against AKI induced by surgical procedures such as ischemia/reperfusion (I/R) or cardiopulmonary bypass. In several murine models of CKD, impaired kidney function was significantly improved by the administration of flavonoids from different sources, alone or in combination with stem cells. In humans, cocoa flavanols were found to have vasculoprotective effects in patients on hemodialysis. Moreover, flavonoids develop antitumor activity against renal carcinoma cells with no toxic effects on normal cells, suggesting a potential therapeutic role in patients with renal carcinoma.
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    Neoastilbin ameliorates sepsis-induced liver and kidney injury by blocking the TLR4/NF-κB pathway
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2024) Xu, Ruiming; Wang, Dawei; Shao, Zhengyi; Li, Xiangbo; Cao, Qiumei
    Sepsis frequently causes systemic inflammatory response syndrome and multiple organ failure in patients. Neoastilbin (NAS) is a flavonoid that plays vital functions in inflammation. This work aims to investigate the protective effects of NAS against sepsisinduced liver and kidney injury and elucidate its underlying mechanisms. The mouse model was established using cecal ligation puncture (CLP) induction. NAS was given to mice by gavage for 7 consecutive days before surgery. Liver and kidney function, oxidative stress, and inflammatory factors in serum or tissues were examined by ELISA or related kits. The expression of relevant proteins was assessed by Western blot. Hematoxylin and eosin and/or periodic acid-Schiff staining revealed that NAS ameliorated the pathological damage in liver and kidney tissues of CLPinduced mice. NAS improved liver and kidney functions, as evidenced by elevated levels of blood urea nitrogen, Creatinine, ALT, and AST in the serum of septic mice. TUNEL assay and the expression of Bcl-2 and Bax showed that NAS dramatically reduced apoptosis in liver and renal tissues. NAS treatment lowered the levels of myeloperoxidase and malondialdehyde, while elevated the superoxide dismutase content in liver and kidney tissues of CLPinduced mice. The levels of inflammatory cytokines (IL6, TNF-α, and IL-1β) in the serum and both tissues of CLP-injured mice were markedly decreased by NAS. Mechanically, NAS downregulated TLR4 expression and inhibited NF-κB activation, and overexpression of TLR4 reversed the protective effects of NAS against liver and kidney injury. Collectively, NAS attenuated CLP-induced apoptosis, oxidative stress, inflammation, and dysfunction in the liver and kidney by restraining the TLR4/NF-κB pathway.
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    The role and mechanism of PKM2 in the development of LPS-induced acute kidney injury
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Wu, Jiajun; Rong, Shu; Zhou, Jing; Yuan, Weijie
    A previous study suggested that pyruvate kinase M2 (PKM2) plays a vital role of metabolic reprogramming in the regulation of the innate inflammatory response, while PKM2 is a sensitive biomarker for nephrotoxicity. In this study, we investigated the role and mechanism of PKM2 in development of LPS-induced acute kidney injury. The AKI model of mice was established using LPS. The serum levels of blood urea nitrogen (Bun), creatinine (Cr), and Cystatin C (CysC) were identified using the enzyme-linked immunosorbent assay (ELISA). Hematoxylin and Eosin staining (H&E) was employed to assess pathological changes in kidney tissues of LPSinduced AKI model. Immunohistochemical staining and Western blot analysis were carried out to determine the expression of apoptosis-related factors at protein levels. We found that Bun, CysC, and Cr were significantly increased in the LPS group compared with the control group. The histopathological assay showed model swollen tubular epithelial cells and the presence of vacuolar degeneration in the LPS-induced AKI. In addition, expression levels of PKM2 significantly increased in the LPS group compared with the control group at both protein and mRNA levels (P<0.01). The inhibition of PKM2 by shikonin notably suppressed the expression of HIF-1α and apoptosis-related factors such as BNIP3, Bax, and Caspase-3, while the inhibition of PKM2 by shikonin significantly improved the histopathological symptoms of LPS-induced AKI. This study demonstrated the potential role of PKM2 in LPSinduced AKI and identified PKM2 as a promising therapeutic target in the treatment of AKI.
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    Transplantation of mesenchymal stem cells preserves podocyte homeostasis through modulation of parietal epithelial cell activation in adriamycin-induced mouse kidney injury model
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Aslam, Rukhsana; Hussain, Ali; Cheng, Kang; Kumar, Vinod; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.
    To determine the role of the transplantation of bone marrow-derived mesenchymal stem cells (MSCs) in podocyte renewal, we studied BALB/C mice with or without adriamycin-induced acute kidney injury. MSCs were transplanted ectopically under the capsule of the left kidney or into the peritoneal cavity after the onset of kidney injury to test their local or systemic paracrine effects, respectively. Adriamycin produced increases in urine protein: creatinine ratios, blood urea nitrogen, and blood pressure, which improved after both renal subcapsular and intraperitoneal MSCs transplants. The histological changes of adriamycin kidney changes regressed in both kidneys and in only the ipsilateral kidney after intraperitoneal or renal subcapsular transplants indicating that the benefits of transplanted MSCs were related to the extent of paracrine factor distribution. Analysis of kidney tissues for p57-positive podocytes showed that MSC transplants restored adriamycin-induced decreases in the abundance of these cells to normal levels, although after renal subcapsular transplants these changes did not extend to contralateral kidneys. Moreover, adriamycin caused inflammatory activation of PECs with coexpression of CD44 and phospho-ERK, which was normalized in both or only ipsilateral kidneys depending on whether MSCs were transplanted in the peritoneal cavity or subcapsular space, respectively