Hinokitiol Prevents Diabetic Acute Kidney Injury by Mitigating ER Stress

Cell Biology International, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

ABSTRACT Acute kidney injury (AKI) in diabetic conditions often advances to chronic disease (CKD), exacerbated by ischemia–reperfusion (IRI) through pathomechanisms such as endoplasmic reticulum (ER) stress and inflammation. Currently, available treatment options for AKI are not uniformly effective, highlighting the need novel interventions. This study aimed examine renoprotective effects of hinokitiol, a natural tropolone compound, against with its capability decrease ER inflammation, along apoptosis. involved NRK‐52E cells grown in‐vitro under high‐glucose subjected 10 mM sodium azide elicit hypoxia/reperfusion (HRI). The expression key markers like binding immunoglobulin protein (BiP), R/PKR‐like kinase (PERK), eukaryotic initiation factor‐2 (eIF2α) well inflammatory proteins was markedly diminished hinokitiol pretreatment (50 μM). Hinokitiol further reduced apoptosis cells. Similarly, in‐vivo study, male Wistar rats STZ‐induced Type 1 diabetes (55 mg/kg, i.p .) were treated 50 100 mg/kg/day . 5 days, followed induction via bilateral IRI. significantly elevated plasma blood urea nitrogen (BUN), creatinine, urinary molecule‐1 (KIM‐1) levels tubular damage rats. also respective expressions rats, demonstrated immunohistochemical analysis immunoblotting. These findings suggest that alleviates modulating PERK/CHOP/NF‐κB axis, likeliness viable therapeutic technique alleviating AKI.

Language: Английский

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Kidney-targeted rhein-loaded liponanoparticles for diabetic nephropathy therapy via size control and enhancement of renal cellular uptake

Theranostics, Journal Year: 2019, Volume and Issue: 9(21), P. 6191 - 6208

Published: Jan. 1, 2019

The optimization of nanoparticle size for passing through glomerular filtration membrane, inefficient renal cellular uptake and rapid urinary excretion nanoparticles are the major obstacles disease treatment via a delivery system. Herein, we propose concept two-step nanoparticular cascade control enhancement to overcome obstacles. Methods: We prepared kidney-targeted rhein (RH)-loaded liponanoparticles (KLPPR) with yolk-shell structure composed by polycaprolactone-polyethyleneimine (PCL-PEI)-based cores kidney targeting peptide (KTP)-modified lipid layers. KLPPR within range 30 ~ 80 nm allowed distribute into membrane KTP (sequence: CSAVPLC) decoration promoted endocytosis non-lysosomal pathway. Results: had an average 59.5±6.2 exhibited high RH loading, sustained release, good stability biocompatibility, in HK-2 cells. In addition, intravenous administration resulted excellent distribution low mice streptozocin-induced diabetic nephropathy (DN), lowered parameters urea nitrogen, serum creatinine index, as well facilitated recovery physiological function improving levels clearance rate suppressing secretion accumulation fibronectin TGF-β1. Conclusion: Definitely, were able target diseased improve therapeutic effect on DN exploiting uptake. This study offers promising strategy diseases using liponanoparticle

Language: Английский

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Acute Kidney Injury: A Bona Fide Complication of Diabetes

Diabetes, Journal Year: 2020, Volume and Issue: 69(11), P. 2229 - 2237

Published: Oct. 14, 2020

The landscape of kidney disease in diabetes has shifted. classical dogma “diabetic nephropathy” progressing through stages albuminuria, leading to decline glomerular filtration rate and end-stage (ESKD), been replaced by a more nuanced understanding the complex heterogeneous nature diabetes. Paralleling this evolution, standardized definitions have resulted growing appreciation that acute injury (AKI) is increasing its incidence rapidly people with are much likely develop AKI than without Here, I propose should be considered complication alongside other complications similarly do not fit neatly into historical microvascular/macrovascular paradigm. In article, we take look at evidence indicating major risk factor for review causes increased risk. We consider long-term implications potential contribution future development chronic disease, ESKD, mortality. Finally, toward strategies better identify new approaches improve outcomes. Recognizing as bona fide open up avenues investigation may ultimately outlook living disease.

Language: Английский

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l -Serine–modified polyamidoamine dendrimer as a highly potent renal targeting drug carrier

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(41), P. 10511 - 10516

Published: Sept. 24, 2018

Effective delivery of drug carriers selectively to the kidney is challenging because their uptake by reticuloendothelial system in liver and spleen, which limits effective treatment diseases results side effects. To address this issue, we synthesized l-serine (Ser)-modified polyamidoamine dendrimer (PAMAM) as a potent renal targeting carrier. Approximately 82% dose was accumulated at 3 h after i.v. injection 111In-labeled Ser-PAMAM mice, while unmodified PAMAM, l-threonine modified l-tyrosine PAMAM resulted accumulations 28%, 35%, 31%, respectively. Single-photon emission computed tomography/computed tomography (SPECT/CT) images also indicated that specifically kidneys. An intrakidney distribution study showed fluorescein isothiocyanate-labeled predominantly proximal tubules. Results cellular LLC-PK1 cells presence inhibitors [genistein, 5-(N-ethyl-N-isopropyl)amiloride, lysozyme] revealed caveolae-mediated endocytosis, micropinocytosis, megalin were associated with accumulation Ser-PAMAM. The efficient angiotensin-converting enzyme (ACE) inhibition effect captopril (CAP), an ACE inhibitor, observed Ser-PAMAM-CAP conjugate. These findings indicate promising carrier for diseases. Thus, demonstrate via Ser modification.

Language: Английский

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Acute kidney injury in diabetic patients: A narrative review

Medicine, Journal Year: 2023, Volume and Issue: 102(21), P. e33888 - e33888

Published: May 26, 2023

Diabetes mellitus (DM) is the most common cause of chronic kidney disease, which leads to end-stage renal failure worldwide. Glomerular damage, arteriosclerosis, and atherosclerosis are contributing factors in diabetic patients, leading progression damage. a distinct risk factor for acute injury (AKI) AKI associated with faster advancement disease patients diabetes. The long-term consequences include development higher cardiovascular cerebral events, poor quality life, high morbidity mortality. In general, not many studies discussed extensively “AKI DM.” Moreover, articles addressing this topic scarce. It also important know so that timely intervention preventive strategies can be implemented decrease injury. Aim review article address epidemiology AKI, its factors, different pathophysiological mechanisms, how differs between nondiabetic therapeutic implications diabetics. increasing occurrence prevalence DM, as well other pertinent issues, motivated us topic.

Language: Английский

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