PMID- 31230218
OWN - NLM
STAT- MEDLINE
DCOM- 20201013
LR  - 20201013
IS  - 1559-0259 (Electronic)
IS  - 1530-7905 (Linking)
VI  - 20
IP  - 1
DP  - 2020 Feb
TI  - Role of ATP-Sensitive Potassium Channel (K(ATP)) and eNOS in Mediating the 
      Protective Effect of Nicorandil in Cyclophosphamide-Induced Cardiotoxicity.
PG  - 71-81
LID - 10.1007/s12012-019-09535-8 [doi]
AB  - Cyclophosphamide (CP) is a widely used chemotherapeutic agent but its clinical 
      usefulness is challenged with different forms of toxicities. No studies have 
      evaluated the possible protective effect of nicorandil (NIC) in CP-induced 
      cardiotoxicity. Our study aimed to investigate this effect by using NIC 
      (3 mg/kg/day) orally for 5 days, in the presence or absence of cardiotoxicity 
      induced by intraperitoneal (i.p.) injection of CP (150 mg/kg) on 4th and 5th 
      days. We confirmed the role of ATP-sensitive potassium channel (K(ATP)) by 
      coadministration of glibenclamide (GP) (5 mg/kg/day) 2 h before NIC (3 mg/kg/day) 
      for 5 days. Moreover, the role of endothelial nitric oxide synthase (eNOS) was 
      confirmed by coadministration of nitro-omega-L-arginine (L-NNA) (25 mg/kg/day) for 
      5 days. Results showed that CP succeeded in induction of cardiotoxicity which 
      manifested by a significant increase in heart weights, creatine kinase-MB 
      (CK-MB), lactate dehydrogenase (LDH), troponin I, cardiac tissue malondialdehyde 
      (MDA), tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL1 beta), and caspase-3 
      levels. Furthermore, CP group showed toxic histopathological changes of marked 
      cardiac damage in addition to a significant decrease in total antioxidant 
      capacity (TAC), superoxide dismutase (SOD), eNOS gene expression, and B cell 
      lymphoma 2 (Bcl2) immunoexpression. NIC succeeded in reversing CP-induced 
      cardiotoxicity by its potassium channel opening effect, stimulating eNOS gene 
      expression, anti-inflammatory, antiapoptotic, and antioxidant properties. 
      Coadministration of GP or L-NNA could diminish the protective effect of NIC. This 
      proves the important role of K(ATP) and eNOS in mediating such protection.
FAU - Refaie, Marwa M M
AU  - Refaie MMM
AUID- ORCID: 0000-0001-6211-9558
AD  - Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, 
      61511, Egypt. marwamonier@yahoo.com.
FAU - Shehata, Sayed
AU  - Shehata S
AD  - Department of Cardiology, Faculty of Medicine, Minia University, El-Minia, 61511, 
      Egypt.
FAU - El-Hussieny, Maram
AU  - El-Hussieny M
AD  - Department of Pathology, Faculty of Medicine, Minia University, El-Minia, 61511, 
      Egypt.
FAU - Abdelraheem, Wedad M
AU  - Abdelraheem WM
AD  - Department of Medical Microbiology and Immunology, Faculty of Medicine, Minia 
      University, El-Minia, 61511, Egypt.
FAU - Bayoumi, Asmaa M A
AU  - Bayoumi AMA
AD  - Department of Biochemistry, Faculty of Pharmacy, Minia University, El-Minia, 
      61511, Egypt.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cardiovasc Toxicol
JT  - Cardiovascular toxicology
JID - 101135818
RN  - 0 (Inflammation Mediators)
RN  - 0 (KATP Channels)
RN  - 0 (Protective Agents)
RN  - 260456HAM0 (Nicorandil)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cardiotoxicity
MH  - *Cyclophosphamide
MH  - Disease Models, Animal
MH  - Heart Diseases/chemically induced/enzymology/pathology/*prevention & control
MH  - Inflammation Mediators/metabolism
MH  - KATP Channels/*agonists/metabolism
MH  - Male
MH  - Myocytes, Cardiac/*drug effects/enzymology/pathology
MH  - Nicorandil/*pharmacology
MH  - Nitric Oxide Synthase Type III/genetics/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Protective Agents/*pharmacology
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - Up-Regulation
OTO - NOTNLM
OT  - Cardiotoxicity
OT  - Cyclophosphamide
OT  - Endothelial nitric oxide synthase
OT  - Glibenclamide
OT  - Nicorandil
OT  - Potassium channel
EDAT- 2019/06/24 06:00
MHDA- 2020/10/21 06:00
CRDT- 2019/06/24 06:00
PHST- 2019/06/24 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/06/24 06:00 [entrez]
AID - 10.1007/s12012-019-09535-8 [pii]
AID - 10.1007/s12012-019-09535-8 [doi]
PST - ppublish
SO  - Cardiovasc Toxicol. 2020 Feb;20(1):71-81. doi: 10.1007/s12012-019-09535-8.