Basic and Clinical Neuroscience Journal
مجله علوم اعصاب پایه و بالینی
BCN
Medical Sciences
http://bcn.iums.ac.ir
137
journal137
2008-126X
2228-7442
10.32598/bcn
en
jalali
1396
12
1
gregorian
2018
3
1
0
Accepted Articles
online
1
fulltext
en
Adrenomedullin Protects Spinal Motor Neurons against Doxorubicin-Induced Toxicity
Cellular and molecular Neuroscience
Cellular and molecular Neuroscience
Original
Original
<div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:200%"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span style="line-height:200%"><span new="" roman="" style="font-family:" times="">Purpose:</span></span></span></b><span style="font-size:12.0pt"><span style="line-height:200%"><span new="" roman="" style="font-family:" times=""> In the present study, the culture of embryonic spinal motor neurons (SMNs) was used to assess the impacts of adrenomedullin (AM) on neurotoxic effects of doxorubicin (DOX).</span></span></span><span style="font-size:12.0pt"><span style="line-height:200%"></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:200%"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span style="line-height:200%">Materials and methods:</span></span></b> <span style="font-size:12.0pt"><span style="line-height:200%"><span new="" roman="" style="font-family:" times="">To prepare the culture of rat embryonic SMNs, spinal cords were isolated from the rat embryos, digested enzymatically, and triturated to obtain spinal cell suspension. Then, the SMNs were purified from the cell suspension using a single gradient of OptiPrep and were cultured. The SMNs were treated with DOX (0.0-100 µM) and AM (3.125-100 nM) and their viability and apoptosis were evaluated using MTT and annexin V flowcytometric assays. Oxidative stress was assessed through the measurement of cellular reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and 8-iso-prostaglandin F2α (iPF2α) levels. Finally, qPCR was employed to determine the expressions of interleukin1-β (IL-1β), inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), SRY-related protein 9 (SOX9), matrix metalloproteinase (MMP)-3 and -13. </span></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:200%"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span style="line-height:200%"><span new="" roman="" style="font-family:" times="">Results:</span></span></span></b><span style="font-size:12.0pt"><span style="line-height:200%"><span new="" roman="" style="font-family:" times=""> The viability of SMNs was decreased following DOX treatment dose-dependently (IC50 = 10.54 µM). DOX increased the cellular ROS, MDA, NO, and iPF2α levels (p<0.001). Additionally, AM reduced DOX-induced cell death dose-dependently (p<0.001). AM (50 nM) pretreatment also reduced the DOX-induced oxidative stress (p<0.01) and -genes expression (p<0.01). </span></span></span></span></span></span><br>
<b><span style="font-size:12.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times="">Conclusion:</span></span></span></b><span style="font-size:12.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times=""> Based on the results, AM might be considered a protective factor against chemotherapy-induced toxicity in SMNs. </span></span></span></div>
Spinal motor neuron, Doxorubicin, Adrenomedullin, Oxidative stress, Inflammation
0
0
http://bcn.iums.ac.ir/browse.php?a_code=A-10-3650-1&slc_lang=en&sid=1
Mohammad Ali
Takhshid
takhshidma@sums.ac.ir
13700319475328460042199
13700319475328460042199
Yes
Professor Division of Medical Biotechnology, Department of Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
Amir
Mahmoodazdeh
Amir.biochem@gmail.com
13700319475328460042200
13700319475328460042200
No
Assistant Professor Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Sayed Mohammad
Shafiee
shafieem@sums.ac.ir
13700319475328460042201
13700319475328460042201
No
Associated Professor Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Mohsen
Sisakht
mohsen.sisakht@gmail.com
13700319475328460042202
13700319475328460042202
No
Assistant Professor Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Zahra
khosdel
Khoshdelz@sums.ac.ir
13700319475328460042203
13700319475328460042203
No
Assistant Professor Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran