PMID- 35074407
OWN - NLM
STAT- MEDLINE
DCOM- 20220221
LR  - 20220221
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 293
DP  - 2022 Mar 15
TI  - Role of JNK, ERK, and p38 MAPK signaling pathway in protective effect of 
      sildenafil in cyclophosphamide-induced placental injury in rats.
PG  - 120354
LID - S0024-3205(22)00054-6 [pii]
LID - 10.1016/j.lfs.2022.120354 [doi]
AB  - AIMS: Chemotherapeutic agents; cyclophosphamide (CYC) is used for treatment of 
      cancer and autoimmune diseases. Grievously, CYC is non-selective as it affects 
      both tumor and healthy cells resulting in systemic toxicity including placenta. 
      The present study aimed to evaluate the effect of phosphodiesterase 5 inhibitor, 
      sildenafil (Sild) on CYC-induced placental injury in rats. MATERIALS AND METHODS: 
      Thirty-two female Wister rats were randomly divided into 4 experimental groups. 
      Group 1: control pregnant group; Group 2: Sild-treated pregnant rats; Group 3: 
      pregnant rats received CYC; Group 4: pregnant rats received Sild and CYC. 
      Placental malondialdehyde (MDA), total nitrite/nitrate (NOx), reduced glutathione 
      (GSH), tumor necrosis factor-alpha (TNF-alpha), platelet growth factor (PlGF), c-Jun 
      N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK), 
      extracellular signal-regulated kinase (ERK) and cleaved caspase-3 were measured. 
      Histological changes, Nuclear Factor kappa-light-chain-enhancer of activated B 
      (NF-kappaB), Connexin 43 (GJA1) and proliferating cell nuclear antigen (PCNA) 
      immuno-expressions were also evaluated. KEY FINDINGS: CYC showed significant 
      decrease in placental GSH, NOx, PlGF, GJA1 and PCNA immuno-expressions but 
      significant increase in placental MDA, TNF-alpha, JNK, P38MAPK, ERK, caspase-3 and 
      NF-kB immuno-expression. Sild showed significant improvement in all oxidative, 
      inflammatory and apoptotic parameters. SIGNIFICANCE: Sild is a promising 
      protective drug against placental injury induced by CYC through antagonizing MAPK 
      (JNK, ERK, and p38) signaling pathway with anti-oxidant, anti-inflammatory and 
      anti-apoptotic effects.
CI  - Copyright (c) 2022. Published by Elsevier Inc.
FAU - Abdelzaher, Walaa Yehia
AU  - Abdelzaher WY
AD  - Department of Pharmacology, Faculty of Medicine, Minia University, Minia 61511, 
      Egypt.
FAU - Bahaa, Haitham Ahmed
AU  - Bahaa HA
AD  - Department of Obstetrics and Gynecology, Faculty of Medicine, Minia University, 
      Minia 61511, Egypt.
FAU - Elkhateeb, Reham
AU  - Elkhateeb R
AD  - Department of Obstetrics and Gynecology, Faculty of Medicine, Minia University, 
      Minia 61511, Egypt.
FAU - Atta, Medhat
AU  - Atta M
AD  - Department of Anatomy, Faculty of Medicine, Minia University, Minia 61511, Egypt.
FAU - Fawzy, Michael Atef
AU  - Fawzy MA
AD  - Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61511, 
      Egypt.
FAU - Ahmed, Amira F
AU  - Ahmed AF
AD  - Department of Histology and Cell Biology, Faculty of Medicine, Minia University, 
      Minia, 61511, Egypt.
FAU - Rofaeil, Remon Roshdy
AU  - Rofaeil RR
AD  - Department of Pharmacology, Faculty of Medicine, Minia University, Minia 61511, 
      Egypt; Department of Pharmacology, Deraya University, New Minia, Egypt. 
      Electronic address: remon.roshdy@deraya.edu.eg.
LA  - eng
PT  - Journal Article
DEP - 20220121
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - BW9B0ZE037 (Sildenafil Citrate)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*toxicity
MH  - Cyclophosphamide/*toxicity
MH  - Female
MH  - MAP Kinase Signaling System/*drug effects/physiology
MH  - Male
MH  - Phosphodiesterase 5 Inhibitors/*pharmacology
MH  - Placenta/*drug effects/pathology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Wistar
MH  - Sildenafil Citrate/*pharmacology
OTO - NOTNLM
OT  - Cyclophosphamide
OT  - ERK
OT  - JNK
OT  - Placental injury
OT  - Sildenafil
OT  - p38 MAPK
EDAT- 2022/01/26 06:00
MHDA- 2022/02/22 06:00
CRDT- 2022/01/25 05:40
PHST- 2021/11/10 00:00 [received]
PHST- 2022/01/14 00:00 [revised]
PHST- 2022/01/18 00:00 [accepted]
PHST- 2022/01/26 06:00 [pubmed]
PHST- 2022/02/22 06:00 [medline]
PHST- 2022/01/25 05:40 [entrez]
AID - S0024-3205(22)00054-6 [pii]
AID - 10.1016/j.lfs.2022.120354 [doi]
PST - ppublish
SO  - Life Sci. 2022 Mar 15;293:120354. doi: 10.1016/j.lfs.2022.120354. Epub 2022 Jan 
      21.