PMID- 31376360
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20190916
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 311
DP  - 2019 Sep 25
TI  - Nicorandil combats doxorubicin-induced nephrotoxicity via amendment of TLR4/P38 
      MAPK/NFkappa-B signaling pathway.
PG  - 108777
LID - S0009-2797(19)30720-3 [pii]
LID - 10.1016/j.cbi.2019.108777 [doi]
AB  - Nicorandil ameliorated doxorubicin-induced nephrotoxicity; this study aimed to 
      show and explain the mechanism of this protection. A precise method was 
      elucidated to study the effect of nicorandil on doxorubicin-induced 
      nephrotoxicity in rats depending on the critical inflammation pathway TLR4/MAPK 
      P38/NFkappa-B. Adult male rats were subdivided into four groups. The 1st group was 
      normal control, the 2nd group received nicorandil (3 mg/kg; p.o., for 4 weeks), 
      the 3rd group received doxorubicin (2.6 mg/kg, i.p., twice per week for 4 weeks), 
      and the fourth group was combination of doxorubicin and nicorandil for 4 weeks. 
      Nephrotoxicity was assessed by biochemical tests through measuring Kidney 
      function biomarkers such as [serum levels of urea, creatinine, albumin and total 
      protein] besides renal kidney injury molecule-1 (KIM-1) and cystatin C], 
      oxidative stress parameters such as [renal tissue malondialdehyde (MDA), reduced 
      glutathione (GSH), SOD, catalase and nrf-2], mediators of inflammation such as 
      [Toll like receptor 4 (TLR-4), Nuclear factor kappa-light-chain-enhancer of 
      activated B cells (NF-kB), p38 MAPK, Interleukin 1 beta (IL-1 beta), and Tumor 
      necrosis factor alpha (TNF-alpha)] and markers of apoptosis [BAX and Bcl-2 in renal 
      tissue]. Finally, our data were supported by histopathology examination. 
      Nicorandil pretreatment resulted in a significant decrease in nephrotoxicity 
      biomarkers, oxidative stress markers, inflammatory mediators and prevented 
      apoptosis through decreasing BAX and increasing Bcl-2 in renal tissues. 
      Nicorandil prevented all the histological alterations caused by doxorubicin. 
      Nicorandil is a promising antidote against doxorubicin-induced nephrotoxicity by 
      neutralizing all toxicity mechanisms caused by doxorubicin through normalizing 
      inflammatory cascade of TLR4/MAPK P38/NFkappa-B.
CI  - Copyright (c) 2019. Published by Elsevier B.V.
FAU - Khames, Ali
AU  - Khames A
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Deraya 
      University, Minia, Egypt; Department of Pharmacology, National Organization for 
      Drug Control and Research (NODCAR), Cairo, Egypt.
FAU - Khalaf, Marwa M
AU  - Khalaf MM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef 
      University, Beni-Suef, Egypt. Electronic address: marwa.khalaf@pharm.bsu.edu.eg.
FAU - Gad, Amany M
AU  - Gad AM
AD  - Department of Pharmacology, National Organization for Drug Control and Research 
      (NODCAR), Cairo, Egypt.
FAU - Abd El-Raouf, Ola M
AU  - Abd El-Raouf OM
AD  - Department of Pharmacology, National Organization for Drug Control and Research 
      (NODCAR), Cairo, Egypt.
FAU - Kandeil, Mohamed Ahmed
AU  - Kandeil MA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef 
      University, Beni-Suef, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20190731
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Havcr1protein, rat)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 260456HAM0 (Nicorandil)
RN  - 80168379AG (Doxorubicin)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Blood Urea Nitrogen
MH  - Cell Adhesion Molecules/blood
MH  - Creatinine/blood
MH  - Doxorubicin/*toxicity
MH  - Glutathione/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Kidney/*drug effects/metabolism/pathology
MH  - Male
MH  - NF-E2-Related Factor 2/metabolism
MH  - NF-kappa B/metabolism
MH  - Nicorandil/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - Superoxide Dismutase/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Doxorubicin
OT  - Inflammation
OT  - Nephrotoxicity
OT  - Nicorandil
EDAT- 2019/08/04 06:00
MHDA- 2019/09/17 06:00
CRDT- 2019/08/04 06:00
PHST- 2019/05/01 00:00 [received]
PHST- 2019/07/16 00:00 [revised]
PHST- 2019/07/31 00:00 [accepted]
PHST- 2019/08/04 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2019/08/04 06:00 [entrez]
AID - S0009-2797(19)30720-3 [pii]
AID - 10.1016/j.cbi.2019.108777 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2019 Sep 25;311:108777. doi: 10.1016/j.cbi.2019.108777. Epub 
      2019 Jul 31.