PMID- 31168342
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 2008-3866 (Print)
IS  - 2008-3874 (Electronic)
IS  - 2008-3866 (Linking)
VI  - 22
IP  - 4
DP  - 2019 Apr
TI  - Empagliflozin alleviates renal inflammation and oxidative stress in 
      streptozotocin-induced diabetic rats partly by repressing HMGB1-TLR4 receptor 
      axis.
PG  - 384-390
LID - 10.22038/ijbms.2019.31788.7651 [doi]
AB  - OBJECTIVES: 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-kappaB 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-alpha) 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.
FAU - Ashrafi Jigheh, Zahra
AU  - Ashrafi Jigheh Z
AD  - Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Ghorbani Haghjo, Amir
AU  - Ghorbani Haghjo A
AD  - Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, 
      Iran.
FAU - Argani, Hassan
AU  - Argani H
AD  - Urology and Nephrology Research Center, Beheshti University of Medical Sciences, 
      Tehran, Iran.
FAU - Roshangar, Leila
AU  - Roshangar L
AD  - Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
FAU - Rashtchizadeh, Nadereh
AU  - Rashtchizadeh N
AD  - Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, 
      Iran.
FAU - Sanajou, Davoud
AU  - Sanajou D
AD  - Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Nazari Soltan Ahmad, Saeed
AU  - Nazari Soltan Ahmad S
AD  - Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Rashedi, Jalil
AU  - Rashedi J
AD  - Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Dastmalchi, Siavoush
AU  - Dastmalchi S
AD  - Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, 
      Iran.
FAU - Mesgari Abbasi, Mehran
AU  - Mesgari Abbasi M
AD  - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, 
      Iran.
LA  - eng
PT  - Journal Article
PL  - Iran
TA  - Iran J Basic Med Sci
JT  - Iranian journal of basic medical sciences
JID - 101517966
PMC - PMC6535193
OTO - NOTNLM
OT  - Diabetic nephropathy
OT  - Empagliflozin
OT  - HMGB1
OT  - Inflammation
OT  - TLR-4
COIS- All authors declare no conflict of interests.
EDAT- 2019/06/07 06:00
MHDA- 2019/06/07 06:01
PMCR- 2019/04/01
CRDT- 2019/06/07 06:00
PHST- 2019/06/07 06:00 [entrez]
PHST- 2019/06/07 06:00 [pubmed]
PHST- 2019/06/07 06:01 [medline]
PHST- 2019/04/01 00:00 [pmc-release]
AID - 10.22038/ijbms.2019.31788.7651 [doi]
PST - ppublish
SO  - Iran J Basic Med Sci. 2019 Apr;22(4):384-390. doi: 
      10.22038/ijbms.2019.31788.7651.