PMID- 30351976
OWN - NLM
STAT- MEDLINE
DCOM- 20190313
LR  - 20211204
IS  - 1205-7541 (Electronic)
IS  - 0008-4212 (Linking)
VI  - 96
IP  - 12
DP  - 2018 Dec
TI  - Protective effect of irbesartan against doxorubicin-induced nephrotoxicity in 
      rats: implication of AMPK, PI3K/Akt, and mTOR signaling pathways.
PG  - 1209-1217
LID - 10.1139/cjpp-2018-0259 [doi]
AB  - Nephrotoxicity is one of the serious undesirable effects related to doxorubicin 
      (DOX). Herein, we have investigated the potential protective effect of irbesartan 
      (IRB) against chronic nephrotoxicity induced by DOX, and the implication of 
      different mechanistic pathways underlying these effects. Rats were treated with 
      either DOX (2.5 mg/kg i.p., 3 times/week) for 2 weeks, and (or) IRB (40 mg/kg, 
      daily) for 3 weeks. IRB prohibited nephrotoxicity induced by DOX, which was 
      evident by the increase in blood urea nitrogen and creatinine levels and 
      histopathological changes. IRB improved DOX-induced alterations in oxidative 
      status by diminishing lipid peroxidation and upregulating the antioxidant 
      enzymes. Also, upon DOX treatment, the renal expression of tumor necrosis 
      factor-alpha, interleukin-6, and caspase-3 were significantly increased; IRB 
      diminished DOX-induced alterations in these parameters. Moreover, DOX 
      significantly decreased the expression level of AMP-activated protein kinase 
      (AMPK). Meanwhile, DOX induced activation of phosphatidylinositol 3-kinase 
      (PI3K)/protein kinase B (Akt/PKB) and mammalian target of rapamycin (mTOR) 
      pathways that cross talked with AMPK. On the contrary, IRB successfully 
      counterbalanced all these effects. Collectively, these outcomes suggest that the 
      modulation of AMPK, PI3K, Akt, and mTOR pathways plays a critical role in 
      conferring the protective effects of IRB against DOX nephrotoxicity.
FAU - Mohamed, Eman A
AU  - Mohamed EA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar 
      University, Cairo, Egypt.
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar 
      University, Cairo, Egypt.
FAU - Ahmed, Hebatalla I
AU  - Ahmed HI
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar 
      University, Cairo, Egypt.
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar 
      University, Cairo, Egypt.
FAU - Zaky, Heba S
AU  - Zaky HS
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar 
      University, Cairo, Egypt.
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar 
      University, Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20181023
PL  - Canada
TA  - Can J Physiol Pharmacol
JT  - Canadian journal of physiology and pharmacology
JID - 0372712
RN  - 0 (Antioxidants)
RN  - 0 (Interleukin-6)
RN  - 0 (Protective Agents)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 80168379AG (Doxorubicin)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - J0E2756Z7N (Irbesartan)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Blood Urea Nitrogen
MH  - Caspase 3/metabolism
MH  - Creatinine/metabolism
MH  - Disease Models, Animal
MH  - Doxorubicin/*pharmacology
MH  - Interleukin-6/metabolism
MH  - Irbesartan/*pharmacology
MH  - Kidney/*drug effects/metabolism
MH  - Lipid Peroxidation/drug effects
MH  - Male
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protective Agents/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - AMPK
OT  - PI3K/Akt
OT  - doxorubicin
OT  - doxorubicine
OT  - irbesartan
OT  - irbesartan
OT  - mTOR
OT  - nephrotoxicity
OT  - nephrotoxicite
OT  - rats
EDAT- 2018/10/24 06:00
MHDA- 2019/03/14 06:00
CRDT- 2018/10/24 06:00
PHST- 2018/10/24 06:00 [pubmed]
PHST- 2019/03/14 06:00 [medline]
PHST- 2018/10/24 06:00 [entrez]
AID - 10.1139/cjpp-2018-0259 [doi]
PST - ppublish
SO  - Can J Physiol Pharmacol. 2018 Dec;96(12):1209-1217. doi: 10.1139/cjpp-2018-0259. 
      Epub 2018 Oct 23.