Folic acid‐induced animal model of kidney disease

Lv, Yan

doi:10.1002/ame2.12194

Cited by 46 publications

(27 citation statements)

References 245 publications

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“…Male mice (8 to 10 weeks old) weighing 20 to 25 g were used in the study. The mice were administered an intraperitoneal injection of folic acid (FA, 250 mg/kg dose) (Sigma) dissolved in NaHCO 3 [ 22 , 23 , 24 ]. The control mice were administered an intraperitoneal injection of vehicle (0.3 mol/L NaHCO 3 ).…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Inhibition of S100A4 Attenuates Fibroblast Activation and Renal Fibrosis

Wen

Jiao

Tran

et al. 2022

Cells

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The TGF-β/Smad3 signaling pathway is an important process in the pathogenesis of kidney fibrosis. However, the molecular mechanisms are not completely elucidated. The current study examined the functional role of S100A4 in regulating TGF-β/Smad3 signaling in fibroblast activation and kidney fibrosis development. S100A4 was upregulated in the kidney in a murine model of renal fibrosis induced by folic acid nephropathy. Further, S100A4 was predominant in the tubulointerstitial cells of the kidney. Pharmacological inhibition of S100A4 with niclosamide significantly attenuated fibroblast activation, decreased collagen content, and reduced extracellular matrix protein expression in folic acid nephropathy. Overexpression of S100A4 in cultured renal fibroblasts significantly facilitated TGF-β1-induced activation of fibroblasts by increasing the expression of α-SMA, collagen-1 and fibronectin. In contrast, S100A4 knockdown prevented TGF-β1-induced activation of fibroblast and transcriptional activity of Smad3. Mechanistically, S100A4 interacts with Smad3 to stabilize the Smad3/Smad4 complex and promotes their translocation to the nucleus. In conclusion, S100A4 facilitates TGF-β signaling via interaction with Smad3 and promotes kidney fibrosis development. Manipulating S100A4 may provide a beneficial therapeutic strategy for chronic kidney disease.

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Section: Methodsmentioning

confidence: 99%

Pharmacological Inhibition of S100A4 Attenuates Fibroblast Activation and Renal Fibrosis

Wen

Jiao

Tran

et al. 2022

Cells

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“…It was reported that single or multiple injections of high-dose folic acid (125–250 mg/kg BW) caused tubular necrosis, oxidative stress and increased creatinine levels in rodents [ 52 , 53 , 54 ]. On the other hand, low-dose folic acid had beneficial effects on the cardiovascular system, and improved hyperhomocysteinemia and diabetes [ 23 , 45 , 55 , 56 ]. The 5-MTHF is biologically active and is the primary form of folate in systemic circulation.…”

Section: Discussionmentioning

confidence: 99%

5-Methyltetrahydrofolate Attenuates Oxidative Stress and Improves Kidney Function in Acute Kidney Injury through Activation of Nrf2 and Antioxidant Defense

et al. 2022

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Oxidative stress is a major mediator of adverse outcomes in acute kidney injury (AKI). Deficiency of micronutrients, such as folate, is common in AKI. Our previous study reported that AKI impaired kidney reabsorption of folate and decreased plasma folate level in rats. The present study investigated the effect of 5-methyltetrahydrofolate (5-MTHF), a biologically active form of folate/folic acid, on AKI-impaired kidney function and oxidative stress. Sprague-Dawley rats developed AKI after kidney ischemia (45 min) and reperfusion (24 h). Injection of 5-MTHF (3 µg/kg body weight) improved kidney function and attenuated oxidative stress with a restoration of glutathione and a reduction of lipid peroxidation in the kidney. Injection of 5-MTHF activated transcription factor Nrf2 and increased the expression of glutathione synthesizing enzymes, superoxide dismutase-1 and heme oxygenase-1 in the kidney. Simulated ischemia-reperfusion through hypoxia-reoxygenation increased oxidative stress in proximal tubular cells. Incubation of cells with 5-MTHF alleviated cell injury and increased antioxidant enzyme expression and intracellular glutathione levels. Inhibition of Nrf2 expression through siRNA transfection abolished the effect of 5-MTHF against oxidative stress. These results suggest that low-dose folic acid can improve kidney function through activation of Nrf2 and restoration of antioxidant defence. Micronutrient supplements may improve clinical outcomes in AKI.

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“…Moreover, numerous diabetic kidney injury biomarkers, such as those recently reported by Pelle et al [ 46 ] and Natesan et al [ 11 ], have also not been systematically and comprehensively evaluated in this NA-STZ animal model. Most studies use popular kidney injury parameters [ 47 ] such as blood urea nitrogen (BUN), serum cystatin C, creatinine, uric acid, or/and estimated glomerular flow rate (eGFR) for the evaluation of diabetic kidney injury after NA-STZ injections. The histopathological staining of kidney is also frequently used for the analysis of kidney injury in this NA-STZ animal model.…”

Section: Renal Pathophysiology In This Na/stz Animal Modelmentioning

confidence: 99%

“…Additionally, this model could also provide a platform for testing the therapeutic effects of stem cells and gene therapy on DN [ 11 ]. For studying multiple kidney disease-causing risk factors, this model could also be combined with other kidney disease animal models, such as those induced by folic acid [ 47 , 124 , 125 , 126 ], cisplatin [ 127 , 128 ], cadmium [ 129 , 130 , 131 ], lipopolysaccharide [ 132 , 133 ], and hypoxia or ischemia reperfusion [ 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 ].…”

Section: Redox-related Mechanisms That Remain To Be Elucidated In Thi...mentioning

confidence: 99%

The Nicotinamide/Streptozotocin Rodent Model of Type 2 Diabetes: Renal Pathophysiology and Redox Imbalance Features

2022

Biomolecules

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Diabetic nephropathy (DN) is a common complication of diabetes mellitus. While there has been a great advance in our understanding of the pathogenesis of DN, no effective managements of this chronic kidney disease are currently available. Therefore, continuing to elucidate the underlying biochemical and molecular mechanisms of DN remains a constant need. In this regard, animal models of diabetes are indispensable tools. This review article highlights a widely used rodent model of non-obese type 2 diabetes induced by nicotinamide (NA) and streptozotocin (STZ). The mechanism underlying diabetes induction by combining the two chemicals involves blunting the toxic effect of STZ by NA so that only a percentage of β cells are destroyed and the remaining viable β cells can still respond to glucose stimulation. This NA-STZ animal model, as a platform for the testing of numerous antidiabetic and renoprotective materials, is also discussed. In comparison with other type 2 diabetic animal models, such as high-fat-diet/STZ models and genetically engineered rodent models, the NA-STZ model is non-obese and is less time-consuming and less expensive to create. Given that this unique model mimics certain pathological features of human DN, this model should continue to find its applications in the field of diabetes research.

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Folic acid‐induced animal model of kidney disease

Cited by 46 publications

References 245 publications

Pharmacological Inhibition of S100A4 Attenuates Fibroblast Activation and Renal Fibrosis

Pharmacological Inhibition of S100A4 Attenuates Fibroblast Activation and Renal Fibrosis

5-Methyltetrahydrofolate Attenuates Oxidative Stress and Improves Kidney Function in Acute Kidney Injury through Activation of Nrf2 and Antioxidant Defense

The Nicotinamide/Streptozotocin Rodent Model of Type 2 Diabetes: Renal Pathophysiology and Redox Imbalance Features

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