scholarly journals Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1166
Author(s):  
Kai-Fan Tsai ◽  
Yung-Lung Chen ◽  
Terry Ting-Yu Chiou ◽  
Tian-Huei Chu ◽  
Lung-Chih Li ◽  
...  

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral glucose-lowering agents. Apart from their glucose-lowering effects, large clinical trials assessing certain SGLT2 inhibitors have revealed cardiac and renal protective effects in non-diabetic patients. These excellent outcomes motivated scientists and clinical professionals to revisit their underlying mechanisms. In addition to the heart and kidney, redox homeostasis is crucial in several human diseases, including liver diseases, neural disorders, and cancers, with accumulating preclinical studies demonstrating the therapeutic benefits of SGLT2 inhibitors. In the present review, we aimed to update recent advances in the antioxidant roles of SGLT2 inhibitors in common but debilitating human diseases. We anticipate that this review will guide new research directions and novel therapeutic strategies for diabetes, cardiovascular diseases, nephropathies, liver diseases, neural disorders, and cancers in the era of SGLT2 inhibitors.

Author(s):  
Jiang Liu ◽  
Jiang Tian ◽  
Komal Sodhi ◽  
Joseph I. Shapiro

AbstractIn different large-scale clinic outcome trials, sodium (Na+)/glucose co-transporter 2 (SGLT2) inhibitors showed profound cardiac- and renal-protective effects, making them revolutionary treatments for heart failure and kidney disease. Different theories are proposed according to the emerging protective effects other than the original purpose of glucose-lowering in diabetic patients. As the ATP-dependent primary ion transporter providing the Na+ gradient to drive other Na+-dependent transporters, the possible role of the sodium–potassium adenosine triphosphatase (Na/K-ATPase) as the primary ion transporter and its signaling function is not explored. Graphic Abstract


HORMONES ◽  
2013 ◽  
Vol 12 (4) ◽  
pp. 483-494 ◽  
Author(s):  
Cláudia Nogueira ◽  
Selma Souto ◽  
Eduardo Vinha ◽  
Daniel Carvalho-Braga ◽  
Davide Carvalho

Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1376
Author(s):  
Laura Lohan ◽  
Florence Galtier ◽  
Thibault Manson ◽  
Thibault Mura ◽  
Audrey Castet-Nicolas ◽  
...  

Background and objectives: Renal failure is a contraindication for some glucose-lowering drugs and requires dosage adjustment for others, particularly biguanides, sulfonylureas, and inhibitors of dipeptidyl peptidase 4. In this study, we assessed adherence to prescription recommendations for glucose-lowering drugs according to renal function in hospitalized diabetic subjects. Materials and Methods: This prospective cohort study was carried out over a 2-year period in a university hospital. Glomerular filtration rate (GFR) was determined by averaging all measurements performed during hospitalization. Glucose-lowering drug dosages were analyzed according to the recommendations of the relevant medical societies. Results: In total, 2071 diabetic patients (53% hospitalized in cardiology units) were examined. GFR was <30 mL/min/1.73 m2 in 13.4% of these patients, 30–44 in 15.1%, 45–60 in 18.3%, and >60 in 53.3%. Inappropriate oral glucose-lowering treatments were administered to 273 (13.2%) patients, including 53 (2.6%) with a contraindication. In cardiology units, 53.1% and 14.3% of patients had GFRs of <60 and <30 mL/min/1.73 m2, respectively, and 179 (15.4%) patients had a contraindication or were prescribed an excessive dose of glucose-lowering drugs. Conclusions: We showed that the burden of inappropriate prescriptions is high in diabetic patients. Given the high number of patients receiving these medications, particularly in cardiology units, a search for potential adverse effects related to these drugs should be performed.


2019 ◽  
Vol 15 (5) ◽  
pp. 349-356 ◽  
Author(s):  
Angus Gill ◽  
Stephen P. Gray ◽  
Karin A. Jandeleit-Dahm ◽  
Anna M.D. Watson

Background: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. Conclusion: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds.


2019 ◽  
Vol 14 (5) ◽  
pp. 442-452 ◽  
Author(s):  
Wenjie Zheng ◽  
Yumin Yang ◽  
Russel Clive Sequeira ◽  
Colin E. Bishop ◽  
Anthony Atala ◽  
...  

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 168
Author(s):  
Isabel Torres-Cuevas ◽  
Iván Millán ◽  
Miguel Asensi ◽  
Máximo Vento ◽  
Camille Oger ◽  
...  

The loss of redox homeostasis induced by hyperglycemia is an early sign and key factor in the development of diabetic retinopathy. Due to the high level of long-chain polyunsaturated fatty acids, diabetic retina is highly susceptible to lipid peroxidation, source of pathophysiological alterations in diabetic retinopathy. Previous studies have shown that pterostilbene, a natural antioxidant polyphenol, is an effective therapy against diabetic retinopathy development, although its protective effects on lipid peroxidation are not well known. Plasma, urine and retinas from diabetic rabbits, control and diabetic rabbits treated daily with pterostilbene were analyzed. Lipid peroxidation was evaluated through the determination of derivatives from arachidonic, adrenic and docosahexaenoic acids by ultra-performance liquid chromatography coupled with tandem mass spectrometry. Diabetes increased lipid peroxidation in retina, plasma and urine samples and pterostilbene treatment restored control values, showing its ability to prevent early and main alterations in the development of diabetic retinopathy. Through our study, we are able to propose the use of a derivative of adrenic acid, 17(RS)-10-epi-SC-Δ15-11-dihomo-IsoF, for the first time, as a suitable biomarker of diabetic retinopathy in plasmas or urine.


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