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Iranian Journal of Basic Medical Sciences، جلد ۲۲، شماره ۴، صفحات ۳۸۴-۳۹۰
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عنوان انگلیسی Empagliflozin alleviates renal inflammation and oxidative stress in streptozotocin-induced diabetic rats partly by repressing HMGB1-TLR4 receptor axis
چکیده انگلیسی مقاله Objective(s): Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, possesses verified anti-inflammatory and anti-oxidative stress effects against diabetic nephropathy. The present investigation aims to examine empagliflozin effects on the renal levels of high mobility group box-1 (HMGB1), a potent inflammatory cytokine, and its respective receptor toll-like receptor-4 (TLR-4) in STZ-induced diabetic rats.Materials and Methods: Empagliflozin at 10 mg/kg per os (p.o.) was administered for 4 weeks, starting 8 weeks after the induction of diabetes. Renal function, kidney inflammation, oxidative stress, and apoptosis markers as well as renal HMGB1, receptor for advanced glycation end products (RAGE), and TLR-4 levels were assessed.Results: In addition to down-regulating NF-κB activity in renal cortices, empagliflozin reduced renal levels of HMGB1, RAGE, and TLR-4. It alleviated renal inflammation as indicated by diminished renal expressions of inflammatory cytokines and chemokines like tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) and also decreased urinary levels of interleukin-6 (IL-6) and alpha-1 acid glycoprotein (AGP). Moreover, empagliflozin ameliorated renal oxidative stress as demonstrated by decreased renal malondialdehyde (MDA) and elevated renal activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX). It also suppressed renal caspase-3, the marker of apoptosis; and furthermore, enhanced renal function noticed by the declined levels of serum urea and creatinine.Conclusion: These findings underline that empagliflozin is able to attenuate diabetes-related elevations in renal HMGB1 levels, an influential inflammatory cytokine released from the necrotic and activated cells, and its correspondent receptors, i.e., RAGE and TLR-4.
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نویسندگان مقاله | Zahra Ashrafi Jigheh
Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran


| Amir Ghorbani Haghjo
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran


| Hassan Argani
Urology and Nephrology Research Center, Beheshti University of Medical Sciences, Tehran, Iran


| Leila Roshangar
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran


| Nadereh Rashtchizadeh
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran


| Davoud Sanajou
Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran


| Saeed Nazari Soltan Ahmad
Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran


| Jalil Rashedi
Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran


| Siavoush Dastmalchi
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran


| Mehran Mesgari Abbasi
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
نشانی اینترنتی http://ijbms.mums.ac.ir/article_12191.html
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زبان مقاله منتشر شده en
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نوع مقاله منتشر شده Original Article
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