Suppression of glutathione system and upregulation of caspase 3-dependent apoptosis mediate rohypnol-induced gastric injury

IF 5.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
R. Akhigbe, D. T. Oluwole, T. E. Adegoke, M. Hamed, D. Anyogu, A. Ajayi
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引用次数: 5

Abstract

ABSTRACT Objectives: This study investigated the impact of rohypnol on gastric tissue integrity. Methods: Forty male Wistar rats were randomized into control, low dose rohypnol-treated, high dose rohypnol-treated, low dose rohypnol-treated recovery and high dose rohypnol-treated recovery groups. Results: Rohypnol caused significant rise in gastric malondialdehyde (MDA), oxidized glutathione (GSSG), nitric oxide (NO), tumour necrotic factor-α (TNF-α), and interleukin-6 (IL-6) levels. Also, rohypnol caused reductions in gastric reduced glutathione (GSH) (as well as GSH/GSSG), and activities of superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), glutathione peroxidase (GPx), cyclo-oxygenase (COX-2). Furthermore, rohypnol upregulated caspase 3 activity and induced gastric DNA damage, evident by a rise in 8-hydroxydeoxyguanosine (8-OHdG) and DNA fragmentation index (DFI) in gastric tissue. These alterations were coupled with reduced gastric weight and distorted gastric cytoarchitecture. Cessation of rohypnol caused a significant but not complete reversal of rohypnol-induced gastric damage. Conclusion: This study revealed that rohypnol induced gastric injury by suppressing glutathione content and COX-2 activity, and upregulating caspase 3-dependent apoptosis, which was partly reversed by rohypnol withdrawal.
谷胱甘肽系统的抑制和caspase 3依赖性细胞凋亡的上调介导罗苯诺诱导的胃损伤
【摘要】目的:研究迷迭香对胃组织完整性的影响。方法:40只雄性Wistar大鼠随机分为对照组、低剂量罗安诺治疗组、高剂量罗安诺治疗组、低剂量罗安诺治疗恢复期组和高剂量罗安诺治疗恢复期组。结果:迷迭香致胃丙二醛(MDA)、氧化谷胱甘肽(GSSG)、一氧化氮(NO)、肿瘤坏死因子-α (TNF-α)、白细胞介素-6 (IL-6)水平显著升高。此外,rohypnol引起胃还原性谷胱甘肽(GSH)(以及GSH/GSSG)和超氧化物歧化酶(SOD)、过氧化氢酶、谷胱甘肽s -转移酶(GST)、谷胱甘肽过氧化物酶(GPx)、环加氧酶(COX-2)活性的降低。此外,rohypnol上调caspase 3活性,诱导胃DNA损伤,表现为胃组织中8-羟基脱氧鸟苷(8-OHdG)和DNA片段化指数(DFI)的升高。这些改变伴随着胃重量减轻和胃细胞结构扭曲。停止服用rohypnol可显著但不完全逆转rohypnol引起的胃损伤。结论:rohypnol通过抑制谷胱甘肽含量和COX-2活性,上调caspase 3依赖性细胞凋亡诱导胃损伤,该作用可被rohypnol停药部分逆转。
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来源期刊
Redox Report
Redox Report 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
28
审稿时长
>12 weeks
期刊介绍: Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.
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