Niclosamide ethanolamine improves kidney injury in db/db mice

Han, Pengxun; Zhan, Hongyue; Shao, Mumin; Wang, Wenjing; Song, Gaofeng; Yu, Xuewen; Zhang, Chunlei; Ge, Na; Yi, Tiegang; Li, Shunmin; Sun, Huili

doi:10.1016/j.diabres.2018.08.003

Cited by 21 publications

(20 citation statements)

References 27 publications

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“…Ethanolamine serum levels also increased with MetS in this study. Previous studies reported that ethanolamine may improve kidney injury in the mouse T2D model 30,31 . We speculate that enhancement of serum ethanolamine might indicate the high risk of kidney injury in these untreated patients.…”

Section: Discussionmentioning

confidence: 69%

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Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population

Wang

Zhuang

et al. 2020

Clinical Translational Sci

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Metabolomics is a promising technology for elucidating the mechanisms of metabolic syndrome (MetS). However, measurements in patients with MetS under different conditions vary. Metabolomics experiments in different populations and pathophysiological conditions are, therefore, indispensable. We performed a serum metabolomics investigation in untreated patients with MetS in the Chinese population. Untreated patients with MetS were recruited to this study. Metabolites were measured using a traditional 1H nuclear magnetic resonance (NMR) experiment followed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS‐DA). Key metabolic pathways were identified by searching the Kyoto Encyclopedia of Genes and Genomes Pathway Database. A total of 28 patients with MetS and 30 healthy subjects were enrolled. All patients were untreated because they were unaware of or neglected to treat their MetS. By 1H NMR, we identified 49 known substances. Following PCA and OPLS‐DA, 36 metabolites were confirmed to be closely associated with MetS compared with the control group; 33 metabolites were increased, whereas 3 metabolites were reduced. Importantly, 14 metabolites that changed in the serum of these untreated patients with MetS were previously unreported. Pathway analysis revealed the top 15 metabolic pathways associated with untreated MetS, which included 3 amino acid metabolic pathways. Our data suggest that untreated patients exhibit a worse pathophysiologic manifestation, which may result in more rapid progression of MetS. Thus, we propose that health education be reinforced to improve the public’s knowledge, attitude, and practice regarding MetS. The rates of “untreated” patients due to unawareness and neglect must be reduced immediately.

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Section: Discussionmentioning

confidence: 69%

“…Previous studies reported that ethanolamine may improve kidney injury in the mouse T2D model. 30,31 We speculate that enhancement of serum ethanolamine might indicate the high risk of kidney injury in these untreated patients. N,N-dimethylglycine and trimethylamine N-oxide are closely associated with elevated HbA 1c .…”

Section: Discussionmentioning

confidence: 91%

Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population

Wang

Zhuang

et al. 2020

Clinical Translational Sci

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“…Excessive mitochondrial ROS levels were associated with mitochondrial injury in mice with diabetic nephropathy (Hwang et al 2012). Mice with diabetic kidney disease exhibited urinary albumin excretion (Han et al 2018(Han et al , 2019 Moreover, studies in dogs (Chacar et al 2017) and cats (Ferlizza et al 2017;Maeda et al 2015) have shown that urinary proteins are one of the early biomarkers of CKD. In addition, the ER is an organelle with several essential functions, including protein synthesis and processing (Chen et al 2010).…”

Section: Introductionmentioning

confidence: 99%

The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice

Wang

Lee

Hsu

et al. 2021

Environ Health Perspect

193

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BACKGROUND: Understanding the epidemic of chronic kidney disease of uncertain etiology may be critical for health policies and public health responses. Recent studies have shown that microplastics (MPs) contaminate our food chain and accumulate in the gut, liver, kidney, muscle, and so on. Humans manufacture many plastics-related products. Previous studies have indicated that particles of these products have several effects on the gut and liver. Polystyrene (PS)-MPs (PS-MPs) induce several responses, such as oxidative stress, and affect living organisms. OBJECTIVES: The aim of this study was to investigate the effects of PS-MPs in kidney cells in vitro and in vivo. METHODS: PS-MPs were evaluated in human kidney proximal tubular epithelial cells (HK-2 cells) and male C57BL/6 mice. Mitochondrial reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, inflammation, and autophagy were analyzed in kidney cells. In vivo, we evaluated biomarkers of kidney function, kidney ultrastructure, muscle mass, and grip strength, and urine protein levels, as well as the accumulation of PS-MPs in the kidney tissue. RESULTS: Uptake of PS-MPs at different concentrations by HK-2 cells resulted in higher levels of mitochondrial ROS and the mitochondrial protein Bad. Cells exposed to PS-MPs had higher ER stress and markers of inflammation. MitoTEMPO, which is a mitochondrial ROS antioxidant, mitigated the higher levels of mitochondrial ROS, Bad, ER stress, and specific autophagy-related proteins seen with PS-MP exposure. Furthermore, cells exposed to PS-MPs had higher protein levels of LC3 and Beclin 1. PS-MPs also had changes in phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (AKT)/mitogen-activated protein kinase (mTOR) signaling pathways. In an in vivo study, PS-MPs accumulated and the treated mice had more histopathological lesions in the kidneys and higher levels of ER stress, inflammatory markers, and autophagy-related proteins in the kidneys after PS-MPs treatment by oral gavage. CONCLUSIONS:The results suggest that PS-MPs caused mitochondrial dysfunction, ER stress, inflammation, and autophagy in kidney cells and accumulated in HK-2 cells and in the kidneys of mice. These results suggest that long-term PS-MPs exposure may be a risk factor for kidney health.

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“…The potential therapeutic effect of niclosamide and its analogues has been reported in many diseases including Parkinson’s disease, cancer, type 2 diabetes, bacterial and viral infection, rheumatoid arthritis, and systemic sclerosis through multiple mechanisms such as uncoupling of oxidative phosphorylation, and modulation of Wnt/β-catenin, mTORC1, STAT3, NF-κB, and Notch signaling pathways [ 81 , 82 ]. Moreover, niclosamide and its analogues have been shown to exert renoprotective effects in various kidney models including unilateral ureteral obstruction, renal ischemia/reperfusion injury, adriamycin nephropathy, as well as db/db and STZ-induced type 1 diabetic kidney injury [ 83 , 84 , 85 , 86 , 87 ]. Despite its promising antifibrotic effect in kidney disease, the underlying mechanism is still not clear.…”

Section: Pharmacological Activation Of Pink1mentioning

confidence: 99%

The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease

Huang

Bian

Cao

et al. 2021

IJMS

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Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.

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Niclosamide ethanolamine improves kidney injury in db/db mice

Cited by 21 publications

References 27 publications

Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population

Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population

The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice

The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease

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