Kazak Filiz, Akalın Pınar Peker, Yarım Gül Fatma, Başpınar Nuri, Özdemir Özgür, Ateş Mehmet Burak, Altuğ Muhammed Enes, Deveci Mehmet Zeki Yılmaz
Department of Biochemistry, Veterinary Faculty, Hatay Mustafa Kemal University, Hatay, Turkey.
Department of Biochemistry, Veterinary Faculty, Ondokuz Mayıs University, Samsun, Turkey.
Int J Neurosci. 2021 Mar 8:1-7. doi: 10.1080/00207454.2021.1896507.
This study was designed to investigate the possible antioxidant, antiapoptotic and neuroprotective effects of nobiletin on cisplatin-induced neurotoxicity rat model by evaluating neurotrophins, antioxidants and histopathology.
Forty male Wistar Albino rats were divided into four groups: control, cisplatin (CIS), cisplatin + nobiletin (CIS + NOB) and nobiletin + cisplatin (NOB + CIS). CIS + NOB was applied nobiletin (10 mg/kg, i.p.) during the last four days whereas NOB + CIS was applied nobiletin during the first four days of the study. Cisplatin (4 mg/kg, i.p. twice a day) was administered to the experimental groups on the 5th day of the study. All rats were sacrificed on the 10th day of the study. BDNF, NGF, G6PD, GPx, tGSH and MDA levels were determined in brain. In addition, routin histolopathological analysis and caspase-3 immunoreactivity assay were conducted.
BDNF concentrations increased in nobiletin-administered groups, compared to Control and CIS and that the increase was statistically significant in NOB + CIS ( < 0.05). It was also found that G6PD activity increased ( < 0.05) in the nobiletin-administered groups, compared to control and CIS. Histopathologically, neuronal degeneration, oedema and gliosis increased in CIS compared to Control, and nobiletin administration decreased neuronal degeneration and oedema compared to CIS ( < 0.05). Cisplatin increased ( < 0.05) caspase-3 immunoreactivity in cerebrovascular endothelium and neurons compared to Control, while nobiletin administration decreased caspase-3 immunoreactivity in cerebrovascular endothelium. Caspase-3 immunoreactivity in neurons decreased only in NOB + CIS ( < 0.05).
Nobiletin increased BDNF concentration and G6PD activity in brain and when evaluated together with histopathological and immunohistochemical findings, it may have antioxidant, antiapoptotic and neuroprotective effects against cisplatin.
本研究旨在通过评估神经营养因子、抗氧化剂和组织病理学，探讨橙皮素对顺铂诱导的神经毒性大鼠模型可能具有的抗氧化、抗凋亡和神经保护作用。
将40只雄性Wistar白化大鼠分为四组：对照组、顺铂组（CIS）、顺铂+橙皮素组（CIS+NOB）和橙皮素+顺铂组（NOB+CIS）。在研究的最后四天，CIS+NOB组腹腔注射橙皮素（10mg/kg），而NOB+CIS组在研究的前四天给予橙皮素。在研究的第5天，给实验组腹腔注射顺铂（4mg/kg，每天两次）。所有大鼠在研究的第10天处死。测定脑中脑源性神经营养因子（BDNF）、神经生长因子（NGF）、葡萄糖-6-磷酸脱氢酶（G6PD）、谷胱甘肽过氧化物酶（GPx）、总谷胱甘肽（tGSH）和丙二醛（MDA）水平。此外，进行常规组织病理学分析和半胱天冬酶-3免疫反应性测定。
与对照组和顺铂组相比，给予橙皮素的组中BDNF浓度升高，且在NOB+CIS组中升高具有统计学意义（P<0.05）。还发现，与对照组和顺铂组相比，给予橙皮素的组中G6PD活性升高（P<0.05）。组织病理学上，与对照组相比，顺铂组神经元变性、水肿和胶质细胞增生增加，与顺铂组相比，给予橙皮素可减少神经元变性和水肿（P<0.05）。与对照组相比，顺铂增加了脑血管内皮细胞和神经元中的半胱天冬酶-3免疫反应性（P<0.05），而给予橙皮素可降低脑血管内皮细胞中的半胱天冬酶-3免疫反应性。仅在NOB+CIS组中神经元中的半胱天冬酶-3免疫反应性降低（P<0.05）。
橙皮素增加了脑中BDNF浓度和G6PD活性，结合组织病理学和免疫组化结果评估，它可能对顺铂具有抗氧化、抗凋亡和神经保护作用。
