Amelioration of fenitrothion induced oxidative DNA damage and inactivation of caspase-3 in the brain and spleen tissues of male rats by N-acetylcysteine
Amelioration of fenitrothion induced oxidative DNA damage and inactivation of caspase-3 in the brain and spleen tissues of male rats by N-acetylcysteine
复制标题
DOI：
10.1016/j.lfs.2019.06.009
复制
发表时间：
2019-08-15
期刊：
影响因子：
6.1
通讯作者：
Arisha, Ahmed Hamed
中科院分区：
文献类型：
--
作者：
Alam, Rasha T.;Imam, Tamer S.;Arisha, Ahmed Hamed
N-乙酰半胱氨酸（NAC）由于其在恢复几种生理参数和缓解氧化应激方面的有益作用而在很大程度上被用作有效的化学保护剂。有趣的是，有人认为NAC的作用机制不仅是抗氧化剂谷胱甘肽的前体，而且可能涉及几种神经营养和炎症途径。杀螟硫磷是一种有机磷杀虫剂，暴露于杀螟硫磷会促进氧化应激，并诱导免疫反应和各种组织（包括大脑和脾脏）的一些有害变化。本研究的主要目的是探讨N-乙酰半胱氨酸对杀螟松中毒引起的雄性大鼠大脑和脾脏组织免疫学和神经学改变以及氧化性DNA损伤的改善作用。我们的研究结果表明，口服暴露于杀螟松30天，导致减少红细胞计数除了白细胞增多，淋巴细胞增多，嗜中性粒细胞。此外，这种给药途径增加了LDH、TNF-α和IL-2的血清水平，同时降低了血清免疫球蛋白（IgG和IgM）浓度。此外，一个显着下调的抗氧化标记物（GSH和SOD）与自由基（MDA）水平的升高被注意到。关于大脑，杀螟硫磷给药抑制AchE活性，增加大脑GABA、5-羟色胺和多巴胺水平。此外，它诱导的氧化性DNA损伤的8-羟基2-脱氧鸟苷（8 OH 2dG）和促凋亡基因，包括Bax和p53的mRNA表达的升高，但Bcl-2的表达减少。N-乙酰半胱氨酸共治疗恢复了这些参数中的大多数的正常生理张力。脑和脾组织中GFAP和Caspase-3的免疫染色分别增强。总之，N-乙酰半胱氨酸补充剂对杀螟硫磷暴露引起的免疫毒性、神经毒性和氧化性DNA损伤具有改善作用。
N-acetylcysteine (NAC) has largely been used as an effective chemo- protective agent owing to their beneficial effect in restoring several physiological parameters and relieving oxidative stress. Interestingly, it has been suggested that NAC mechanisms of action extend beyond being a precursor to the antioxidant glutathione and that they may involve several neurotropic and inflammatory pathways. Exposure to fenitrothion, an organophosphorus insecticide, promotes oxidative stress and induces several deleterious changes in the immune response and various tissues including cerebrum and spleen. The main objective of our study was to investigate ameliorative efficacy of N-acetylcysteine for immunological and neurological alterations and oxidative DNA damage induced by fenitrothion toxicity in cerebrum and spleen tissues of male rats. Our results revealed that oral exposure to fenitrothion for 30 days caused a reduction in the erythrocyte count in addition to leukocytosis, lymphocytosis, and neutrophilia. Also, this route of administration increased the serum levels of LDH, TNF-alpha, and IL-2 with reduction in serum immunoglobulins (IgG & IgM) concentrations. Furthermore, a significant downregulation in the antioxidant markers (GSH & SOD) with an elevation of free radical (MDA) levels were noticed. Regarding the brain, fenitrothion administration inhibited AchE activity and increased brain GABA, serotonin and dopamine levels. Moreover, it induced an elevation in oxidative DNA damage indicated by 8-hydroxy 2-deoxyguanosine (8OH2dG) and mRNA expression of pro-apoptotic genes, including Bax, and p53, but Bcl-2 expression was reduced. N-acetylcysteine co-treatment restored the normal physiological tone in most of these parameters. Immunostaining for GFAP and Caspase-3 markers in the brain and spleen tissues were increased respectively. In conclusion, N-acetylcysteine supplementation has an ameliorative effect against immunotoxic, neurotoxic and oxidative DNA damage induced by fenitrothion exposure.