PMID- 36587501
OWN - NLM
STAT- MEDLINE
DCOM- 20230208
LR  - 20230213
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 115
DP  - 2023 Feb
TI  - Agomelatine improves streptozotocin-induced diabetic nephropathy through 
      melatonin receptors/SIRT1 signaling pathway.
PG  - 109646
LID - S1567-5769(22)01131-6 [pii]
LID - 10.1016/j.intimp.2022.109646 [doi]
AB  - INTRODUCTION: Diabetic nephropathy (DN) is a major cause of end-stage renal 
      disease (ESRD). Agomelatine, a melatonin receptor agonist, has a potent 
      anti-inflammatory activity. The current study aimed to determine the ameliorative 
      anti-inflammatory effect of agomelatine against DN. METHODS: We used 10 % 
      fructose with streptozotocin (STZ) to induce DN in male Wistar rats. Diabetic 
      rats were treated with agomelatine in presence or absence of melatonin receptor 
      antagonist (luzindole) or Sirtuin1 (SIRT1) inhibitor (EX527). SIRT1 expression 
      was measured by qRT-PCR and immunohistochemical analysis. The expression of 
      nuclear factor kappa-light-chain-enhancer of activated B cells (NFkappaB), 
      5'adenosine monophosphate-activated protein kinase (AMPK), intercellular adhesion 
      molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), and monocyte 
      chemoattractant protein-1 (MCP-1) were measured using ELISA. Histological 
      assessment was performed using hematoxylin and eosin-stained renal sections. 
      RESULTS: Fructose and STZ treatment induced diabetes, insulin resistance, and 
      renal damage accompanied by reduced SIRT1 expression, increased NFkappaB activation, 
      and decreased AMPK phosphorylation in the kidney. Agomelatine treatment improved 
      kidney histology and function and upregulated SIRT1 expression (2-fold). 
      Inhibition of melatonin receptors and SIRT1 activity increased NFkappaB 
      phosphorylation (2.13 and 1.98-folds, respectively), reduced AMPK activation 
      (0.51 and 0.53-folds, respectively), increased inflammatory markers ICAM-1 (2.16 
      and 2.23-folds, respectively), VCAM-1 (2.19 and 2.26-folds, respectively), and 
      MCP-1(2.84 and 3.12-folds, respectively), and inhibited the ameliorative effect 
      of agomelatine on kidney structure and function. CONCLUSION: Our findings reveal 
      the ameliorative anti-inflammatory activity of agomelatine against STZ-induced DN 
      and this effect is SIRT1- and melatonin receptor-dependent. Therefore, 
      agomelatine may be beneficial to prevent the development of ESRD from diabetes 
      mellitus.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Mahmoud, Nevertyty M
AU  - Mahmoud NM
AD  - Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, 
      Zagazig, Egypt. Electronic address: NMMahmud@medicine.zu.edu.eg.
FAU - Elshazly, Shimaa M
AU  - Elshazly SM
AD  - Pharmacology and Toxicology Department, Faculty of Pharmacy, Zagazig University, 
      Zagazig, Egypt. Electronic address: shaimaa.elshazly@su.edu.eg.
FAU - Hassan, Arwa A
AU  - Hassan AA
AD  - Pharmacology and Toxicology Department, Faculty of Pharmacy and Pharmaceutical 
      Industries, Sinai University, El-Arish, Egypt. Electronic address: 
      arwa.ahmed@su.edu.eg.
FAU - Soliman, Eman
AU  - Soliman E
AD  - Pharmacology and Toxicology Department, Faculty of Pharmacy, Zagazig University, 
      Zagazig, Egypt. Electronic address: solimane@zu.edu.eg.
LA  - eng
PT  - Journal Article
DEP - 20221230
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Receptors, Melatonin)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - 5W494URQ81 (Streptozocin)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - JL5DK93RCL (Melatonin)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (NF-kappa B)
RN  - 0 (Anti-Inflammatory Agents)
RN  - EC 3.5.1.- (Sirt1 protein, rat)
SB  - IM
MH  - Rats
MH  - Male
MH  - Animals
MH  - *Diabetic Nephropathies/drug therapy/metabolism
MH  - Receptors, Melatonin/therapeutic use
MH  - Sirtuin 1/metabolism
MH  - Streptozocin
MH  - Intercellular Adhesion Molecule-1
MH  - AMP-Activated Protein Kinases/metabolism
MH  - *Diabetes Mellitus, Experimental/metabolism
MH  - *Melatonin/therapeutic use/pharmacology
MH  - Vascular Cell Adhesion Molecule-1
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - NF-kappa B/metabolism
MH  - Anti-Inflammatory Agents/pharmacology
MH  - *Kidney Failure, Chronic
OTO - NOTNLM
OT  - AMPK
OT  - Agomelatine
OT  - Diabetic nephropathy
OT  - Melatonin receptors
OT  - NFkappaB
OT  - SIRT1
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/01/02 06:00
MHDA- 2023/02/09 06:00
CRDT- 2023/01/01 18:10
PHST- 2022/10/16 00:00 [received]
PHST- 2022/12/17 00:00 [revised]
PHST- 2022/12/24 00:00 [accepted]
PHST- 2023/01/02 06:00 [pubmed]
PHST- 2023/02/09 06:00 [medline]
PHST- 2023/01/01 18:10 [entrez]
AID - S1567-5769(22)01131-6 [pii]
AID - 10.1016/j.intimp.2022.109646 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Feb;115:109646. doi: 10.1016/j.intimp.2022.109646. Epub 
      2022 Dec 30.