Adrenomedullin protects rat dorsal root ganglion neurons against doxorubicin-induced toxicity by ameliorating oxidative stress | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 12، دوره 23، شماره 9، آذر 2020، صفحه 1197-1206 اصل مقاله (1.18 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2020.45134.10514 | ||
| نویسندگان | ||
| Amir Mahmoodazdeh1؛ Sayed Mohammad Shafiee* 1، 2؛ Mohsen Sisakht1؛ Zahra Khoshdel1؛ Mohammad Ali Takhshid3 | ||
| 1Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran | ||
| 2Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran | ||
| 3Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran | ||
| چکیده | ||
| Objective(s): Despite effective anticancer effects, the use of doxorubicin (DOX) is hindered due to its cardio and neurotoxicity. The neuroprotective effect of adrenomedullin (AM) was shown in several studies. The present study aimed to evaluate the possible protective effects of AM against DOX-induced toxicity in dorsal root ganglia (DRGs) neurons. Materials and Methods: Rat embryonic DRG neurons were isolated and cultured. The effect of various concentrations of DOX (0.0 to 100 µM) in the absence or presence of AM (3.125 -100 nM) on cell death, apoptosis, oxidative stress, expression of tumor necrosis-α (TNF-α), interleukin1- β (IL-1β), inducible nitric oxide synthase (iNOS), matrix metalloproteinase (MMP) 3 and 13, and SRY-related protein 9 (SOX9) were examined. Results: Based on MTT assay data, DOX decreased the viability of DRG neurons in a dose and time-dependent manner (IC50=6.88 µm) while dose-dependently, AM protected DRG neurons against DOX-induced cell death. Furthermore, results of annexin V apoptosis assay revealed the protective effects of AM (25 nm) against DOX (6.88 µM)-induced apoptosis and necrosis of DRG neurons. Also, AM significantly ameliorated DOX-induced oxidative stress in DRG neurons. Real-time PCR results showed a significant increase in the expression of TNF-α, IL-1β, iNOS, MMP 3, and MMP 13, and a decrease in the expression of SOX9 following treatment with DOX. Treatment with AM (25 nM) significantly reversed the effects of DOX on the above-mentioned genes expression. Conclusion: Our findings suggest that AM can be considered a novel ameliorating drug against DOX-induced neurotoxicity. | ||
| کلیدواژهها | ||
| Adrenomedullin؛ Dorsal root ganglia؛ Doxorubicin؛ Inflammation؛ Oxidative stress | ||
| مراجع | ||
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