Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

Zhang, Jing; Fan, Ying; Zeng, Chuchu; He, Li; Wang, Niansong

doi:10.3390/nu8100589

Cited by 29 publications

(25 citation statements)

References 40 publications

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“…Renal tissues from the mice were fixed for 24 h at 20˚C in 10% neutral formalin, embedded in paraffin, manually sectioned into 4-µm thick tissue sections and stained with hematoxylin and eosin (H&e), periodic acid-Schiff (PaS) and Masson reagent as previously described (19,20). The paraffin-embedded renal tissue sections were analyzed using immunohistochemistry as described in our previous study (19). Briefly, after dewaxing and hydration, the slides were heated in sodium citrate buffer (10 mM; pH 6) for 10 min at 100˚C and incubated with hydrogen peroxide (0.3%) for 10 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…Tissues or cells were lysed with riPa buffer (Beyotime institute of Biotechnology) containing protease and phosphatase inhibitor cocktail, and the protein concentration was measured using the bicinchoninic acid protein assay kit (Bio-rad laboratories, inc.). The protein samples (40 µg per lane for tissue; 30 µg per lane for cells) were separated via SdS-PaGe on 10% gels and transferred to PVdF membranes, as described in our previous study (19). after blocking with PBST containing 3% BSa for 1 h at room temperature, the membranes were incubated with the following primary antibodies overnight at 4˚C: i) GRP78 (1:1,000; Cell Signaling Technology, Inc.; cat.…”

Section: Rna Extraction and Reverse Transcription-quantitative (Rt-q)mentioning

confidence: 99%

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Resveratrol decreases high glucose‑induced apoptosis in renal tubular cells via suppressing endoplasmic reticulum stress

Zhang

Dong

Ding³

et al. 2020

Mol Med Rep

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diabetic nephropathy (dn) is the second most common complication of diabetes mellitus after cardiovascular complications. endoplasmic reticulum (er) stress is known to be associated with dn. resveratrol (rSV) exhibits anti-oxidative, anti-inflammatory and cytoprotective effects. Therefore, the aims of the present study were to investigate the role of rSV in the inhibition of high concentration glucose (HG)-induced apoptosis in renal tubular cells, as well as to examine the protective effects of rSV against diabetes-mediated renal damage via inhibition of er stress in dn. rSV was orally administered to diabetic db/db mice once a day for 12 consecutive weeks. compared with untreated db/db mice, treating db/db mice with RSV significantly decreased urine albumin excretion and the urine albumin to creatinine ratio, and attenuated renal histopathological injury. Furthermore, rSV treatment resulted in decreased expression levels of glucose-regulated protein of 78 kda and c/eBP-homologous protein (two er stress markers) and caspase12 in murine kidneys. rSV administration also inhibited the apoptosis of nrK-52e cells and activation of the er stress signal transduction pathway induced by HG treatment in vitro. collectively, the present results indicated that rSV protected renal tubular cells against HG-induced apoptosis in dn by suppressing er stress.

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Section: Methodsmentioning

confidence: 99%

Section: Rna Extraction and Reverse Transcription-quantitative (Rt-q)mentioning

confidence: 99%

Resveratrol decreases high glucose‑induced apoptosis in renal tubular cells via suppressing endoplasmic reticulum stress

Zhang

Dong

Ding³

et al. 2020

Mol Med Rep

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“…Moreover, it was found that administration of TUDCA at the prediabetic stage resulted in a marked reduction of diabetes incidence in two different mouse models of type1 diabetes (Engin et al 2013). Later, Zhang et al (2016) treated diabetic mice with intraperitoneal TUDCA and noted a significant reduction of blood glucose level with a significant decreased expression of ER stress markers along with decreases in ER stress-associated apoptotic markers.…”

Section: Discussionmentioning

confidence: 99%

Potential prophylactic effect of chemical chaperones for alleviation of endoplasmic reticulum stress in experimental diabetic cataract

et al. 2019

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Background: Imbalance between protein synthesis and endoplasmic reticulum (ER) capacity to modify and fold proteins lead to the accumulation of unfolded proteins resulting in ER stress and apoptosis. Chaperones are major defense molecules assisting in protein folding, transport, and cellular signaling. ER stress plays a major role in the pathogenesis of diabetes mellitus (DM) and its complications, e.g., diabetic cataract. In the present investigation, the chemical chaperones 4-phenylbutyric acid (4-PBA), tauroursodeoxycholic acid (TUDCA), and trimethylamine N-oxide (TMAO) are used as potential therapeutic agents for alleviation of DM-induced ER stress and diabetic cataract in rats. Animals are subjected to biochemical analysis of blood and lenses for ER stress and apoptosis markers. Moreover, ophthalmologic examination and histopathologic examination of the lenses were done to confirm the results. Results: Both ophthalmic and lens histopathologic examination revealed that treatment with 4-PBA and TUDCA retarded the occurrence of cataract markedly. Whereas, treatment with TMAO caused a partial improvement of cataract. Moreover, biochemical tests showed that both 4-PBA and TUDCA produced a remarkable improvement in the ER marker levels (VEGF and caspase-12), GSH, MDA, TAC levels in lens tissues. On the other hand, TMAO had no significant effect on these parameters. However, Western blot analysis of lens homogenates showed a suppressed expression of GRP78 and CHOP after treatment with 4-PBA, TUDCA, and TMAO. Moreover, all treated groups showed a significant improvement of lens soluble proteins and their UV spectra absorption. A significant improvement in fasting blood sugar, GSH, serum MDA, and TAC were noted in all treated groups. 4-PBA produced a significant decrease in insulin resistance, whereas TUDCA and TMAO showed insignificant change. Conclusion: The present research found that the tested chaperones could be used as a therapeutic approach for clinically relevant disorders featuring ER dysfunction such as DM and for reducing its complications in the eye mainly cataract. However, TUDCA and 4-PBA were found to have a more potential efficacy in reducing most of the tested parameters as compared to TMAO.

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“…40 Short-term treatment with TUDCA was also recently shown to protect against folic acid nephropathy in a mouse model of the disease. 43,44 In this study, we hypothesized that TUDCA treatment would prevent the development of proteinuria, albuminuria and renal glomerular and/or tubular injury in a model of salt-sensitive hypertension, the ET B -deficient rat. 43,44 In this study, we hypothesized that TUDCA treatment would prevent the development of proteinuria, albuminuria and renal glomerular and/or tubular injury in a model of salt-sensitive hypertension, the ET B -deficient rat.…”

mentioning

confidence: 99%

“…41 More recent studies report beneficial effects of TUDCA treatment against aldosterone-infused renal injury 42 and diabetic nephropathy. 43,44 In this study, we hypothesized that TUDCA treatment would prevent the development of proteinuria, albuminuria and renal glomerular and/or tubular injury in a model of salt-sensitive hypertension, the ET B -deficient rat. We further examined whether TUDCA treatment would blunt renal apoptosis and inflammation in response to a high salt diet in the ET B -deficient rat model.…”

mentioning

confidence: 99%

Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt‐induced renal injury and inflammation

et al. 2018

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Aim: Chronic high salt intake exaggerates renal injury and inflammation, especially with the loss of functional ET B receptors. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone and bile salt that is approved for the treatment of hepatic diseases. Our aim was to determine whether TUDCA is reno-protective in a model of ET B receptor deficiency with chronic high salt-induced renal injury and inflammation. Methods: ET B -deficient and transgenic control rats were placed on normal (0.8% NaCl) or high salt (8% NaCl) diet for 3 weeks, receiving TUDCA (400 mg/kg/d; ip) or vehicle. Histological and biochemical markers of kidney injury, renal cell death and renal inflammation were assessed. Results: In ET B -deficient rats, high salt diet significantly increased glomerular and proximal tubular histological injury, proteinuria, albuminuria, excretion of tubular injury markers KIM-1 and NGAL, renal cortical cell death and renal CD4 + T cell numbers. TUDCA treatment increased proximal tubule megalin expression as well as prevented high salt diet-induced glomerular and tubular damage in ET B -deficient rats, as indicated by reduced kidney injury markers, decreased glomerular permeability and proximal tubule brush border restoration, as well as reduced renal inflammation. However, TUDCA had no significant effect on blood pressure. Conclusions: TUDCA protects against the development of glomerular and proximal tubular damage, decreases renal cell death and inflammation in the renal cortex in rats with ET B receptor dysfunction on a chronic high salt diet. These results highlight the potential use of TUDCA as a preventive tool against chronic high salt induced renal damage. K E Y W O R D SCD4 + T cells, cell death, ET B receptors, high salt diet, renal injury

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Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

Cited by 29 publications

References 40 publications

Resveratrol decreases high glucose‑induced apoptosis in renal tubular cells via suppressing endoplasmic reticulum stress

Resveratrol decreases high glucose‑induced apoptosis in renal tubular cells via suppressing endoplasmic reticulum stress

Potential prophylactic effect of chemical chaperones for alleviation of endoplasmic reticulum stress in experimental diabetic cataract

Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt‐induced renal injury and inflammation

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