PMID- 36525794
OWN - NLM
STAT- MEDLINE
DCOM- 20230105
LR  - 20230111
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 114
DP  - 2023 Jan
TI  - Liraglutide ameliorates gentamicin-induced acute kidney injury in rats via 
      PGC-1alpha- mediated mitochondrial biogenesis: Involvement of PKA/CREB and 
      Notch/Hes-1 signaling pathways.
PG  - 109578
LID - S1567-5769(22)01063-3 [pii]
LID - 10.1016/j.intimp.2022.109578 [doi]
AB  - Acute kidney injury (AKI) is a challenging side effect which may clinically 
      impede the use of gentamicin (GM). The present study explored the impact of 
      liraglutide (Lir) on GM-induced kidney injury in rats. Lir (0.2 and 0.4 mg/kg, 
      s.c) was given for 10 days (a dose/day) starting 3 days before giving GM 
      (100 mg/kg, i.p) once daily for 7 days. Interestingly, Lir notably ameliorated 
      GM-induced elevated levels of renal injury markers; urea and creatinine. 
      Moreover, Lir remarkably mitigated malondialdehyde (MDA) level and elevated 
      glutathione (GSH) level as well as superoxide dismutase (SOD) activity. Also, Lir 
      pre-treatment notably diminished inflammatory markers levels; interleukin-1beta 
      (IL-1beta), tumor necrosis factor alpha (TNF-alpha), vascular cell adhesion molecule 
      (VCAM), monocyte chemoattractant protein 1 (MCP-1) and interferon gamma (INF-gamma). 
      In addition, Lir significantly replenished expression of Peroxisome 
      proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), Protein kinase 
      A (PKA), cAMP response element-binding protein (CREB), nuclear Nuclear factor 
      erythroid 2-related factor 2 (Nrf2), heme Oxygenase-1 (HO-1), B-cell lymphoma 2 
      (Bcl-2), and remarkably attenuated expression of Notch homolog 1 (Notch1), Hairy 
      and enhancer of split-1 (Hes-1), Bcl-2-associated X (Bax), cleaved caspase 3 and 
      nuclear Nuclear factor Kappa B (NF-kappaB (p65)). The nephroprotective activity of 
      Lir was further confirmed by histopathological examination as well as 
      transmission electron microscopy (TEM). In conclusion Lir achieved its 
      nephroprotective effects through the amelioration of oxidative stress, 
      inflammatory and apoptotic manifestations. It is worth-mentioning that the 
      current study is the first to focus on the involvement of mitochondrial 
      biogenesis and its upstream regulators, PKA/CREB and Notch/Hes-1 signaling 
      pathways in the nephroprotective potentials of Lir. The attenuation of the 
      aforementioned injurious aspects is partially attributed to the improvement of 
      the mitochondrial status as demonstrated by elevated PGC-1alpha expression via 
      acceleration of PKA/CREB and abatement of Notch/Hes-1 signaling pathways.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Elkhoely, Abeer
AU  - Elkhoely A
AD  - Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, 
      Cairo, Egypt. Electronic address: abeerelkhoely@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20221214
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 839I73S42A (Liraglutide)
RN  - 0 (Gentamicins)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Liraglutide/pharmacology/therapeutic use
MH  - Gentamicins
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Organelle Biogenesis
MH  - Signal Transduction
MH  - NF-kappa B/metabolism
MH  - *Acute Kidney Injury/chemically induced/drug therapy/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
OTO - NOTNLM
OT  - Gentamicin
OT  - Kidney injury
OT  - Liraglutide
OT  - Mitochondrial biogenesis
OT  - PGC-1alpha
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- 2022/12/17 06:00
MHDA- 2023/01/06 06:00
CRDT- 2022/12/16 18:19
PHST- 2022/08/07 00:00 [received]
PHST- 2022/12/06 00:00 [revised]
PHST- 2022/12/08 00:00 [accepted]
PHST- 2022/12/17 06:00 [pubmed]
PHST- 2023/01/06 06:00 [medline]
PHST- 2022/12/16 18:19 [entrez]
AID - S1567-5769(22)01063-3 [pii]
AID - 10.1016/j.intimp.2022.109578 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Jan;114:109578. doi: 10.1016/j.intimp.2022.109578. Epub 
      2022 Dec 14.