Ajayi A F, Akhigbe R E
Reproductive Physiology and Bioinformatics Research Unit, Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
Department of Human Physiology, Faculty of Basic Medical Sciences, Baze University, Abuja, Nigeria.
Heliyon. 2021 Jul 3;7(7):e07481. doi: 10.1016/j.heliyon.2021.e07481. eCollection 2021 Jul.
Codeine, a common drug of abuse, has been reported to induce organ damage; however, there are scanty available data on the effects of codeine on the brain.
Thus, we tested the hypothesis that redox dysregulation and inflammation of the brain induced by codeine exposure is 8-OHdG and/or caspase 3-dependent.
New Zealand White rabbits () received vehicle (control; n = 7), low-dose codeine (4 mg/kg/day ; n = 6), or high-dose codeine (10 mg/kg/day ; n = 6) for six weeks. Body weight was checked before and after the study.
Findings showed that codeine exposure resulted in redox dysregulation (evident by elevated MDA and HO accompanied by reduced enzymatic antioxidant activities), elevated MPO activity, and distorted cytoarchitecture of the brain tissue. The observed codeine-induced redox imbalance and brain inflammation was accompanied by depletion of neuronal and purkinje cells, reduced AchE activity, and elevated 8-OHdG levels and caspase 3 activity.
The current study demonstrates that chronic codeine use induces oxido-inflammatory response and apoptosis of the brain tissue that is associated with neuronal and purkinje cells injury, and impaired AchE activity through 8-OHdG and/or caspase 3-dependent pathway.
可待因是一种常见的滥用药物，据报道可导致器官损伤；然而，关于可待因对大脑影响的现有数据很少。
因此，我们检验了这样一个假设，即可待因暴露诱导的大脑氧化还原失调和炎症是依赖8-羟基脱氧鸟苷（8-OHdG）和/或半胱天冬酶3的。
新西兰白兔（）接受载体（对照组；n = 7）、低剂量可待因（4毫克/千克/天；n = 6）或高剂量可待因（10毫克/千克/天；n = 6），为期六周。在研究前后检查体重。
研究结果表明，可待因暴露导致氧化还原失调（表现为丙二醛（MDA）和过氧化氢（HO）升高，同时酶促抗氧化活性降低）、髓过氧化物酶（MPO）活性升高以及脑组织细胞结构扭曲。观察到的可待因诱导的氧化还原失衡和脑部炎症伴随着神经元和浦肯野细胞的减少、乙酰胆碱酯酶（AchE）活性降低、8-OHdG水平升高和半胱天冬酶3活性升高。
当前研究表明，长期使用可待因会诱导脑组织的氧化炎症反应和细胞凋亡，这与神经元和浦肯野细胞损伤以及通过8-OHdG和/或半胱天冬酶3依赖途径导致的AchE活性受损有关。
