Treadmill Exercise Training Ameliorates Apoptotic Cells and DNA Oxidation in the Cerebral Cortex of Rats Exposed to Chronic Ketamine Abuse

IF 3.1 3区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Addiction Biology Pub Date : 2025-03-10 DOI:10.1111/adb.70025

Salar Sabziparvar, Kazem Khodaei, Javad Tolouei Azar

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Abstract

Background

Ketamine abuse damages brain function and structure, increasing reactive oxygen species and apoptosis in the cerebral cortex, but moderate-intensity continuous training (MICT) can enhance antioxidant defences and reduce apoptosis. Therefore, we aimed to answer whether MICT can reduce the side effects of chronic ketamine abuse.

Method

24 Wistar rats were split into control (CON), ketamine abuse (KET), exercise after ketamine withdrawal (KET + EX), and non-intervention ketamine withdrawal (KET + WD) groups. Ketamine intervention groups received 50 mg/kg/day ketamine for 8 weeks; KET + EX underwent 5 MICT sessions/week at 60–75% VO2max for 8 weeks post-withdrawal. Post-sampling of cerebral cortex, we evaluated histological changes, apoptotic cell numbers, Bax, Bcl-2, Caspase-3 mRNA/protein, 8-oxo-2′-deoxyguanosine (OXO) expression, glutathione peroxidase (GPX) and glutathione reductase (GR) mRNA and other oxidative stress and antioxidant markers levels. Effect sizes (ES) were used to assess group differences.

Results

MICT significantly reduced apoptotic cells (ES = 14.24, p < 0.0001), decreased Bax and caspase-3 protein expression, and increased Bcl-2 compared to the KET group (Bax: ES = 2.77, p = 0.005; caspase-3: ES = 7.73, p < 0.0001; Bcl-2: ES = 12.11, p < 0.001). It also lowered Bax and caspase-3 mRNA (Bax: ES = 4, p = 0.014; caspase-3: ES = 2.29, p = 0.024). MICT reduced OXO and increased GR and GPX mRNA and nitric oxide (NO) level (GR: ES = 2.02, p = 0.016; GPX: ES = 1.98, p = 0.035; OXO: ES = 11.39, p < 0.0001; NO: ES = 3.52, p = 0.003). Levels of malondialdehyde, myeloperoxidase, glutathione, superoxide dismutase, and catalase remained unchanged between groups.

Conclusion

MICT seems effective in reducing apoptosis and oxidative damage in the cerebral cortex of rats with long-term ketamine abuse.

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跑步机运动训练改善慢性氯胺酮滥用大鼠大脑皮层凋亡细胞和DNA氧化

氯胺酮滥用会损害大脑功能和结构，增加大脑皮层的活性氧和细胞凋亡，但中强度连续训练（MICT）可以增强抗氧化防御，减少细胞凋亡。因此，我们的目的是回答MICT是否可以减少慢性氯胺酮滥用的副作用。方法将24只Wistar大鼠分为对照组（CON）、氯胺酮滥用组（KET）、氯胺酮戒断后运动组（KET + EX）和无干预氯胺酮戒断组（KET + WD）。氯胺酮干预组给予氯胺酮50 mg/kg/d，持续8周；KET + EX在停药后8周内以60-75%最大摄氧量进行5次MICT /周。采集后观察脑组织组织学变化、凋亡细胞数量、Bax、Bcl-2、Caspase-3 mRNA/蛋白、8-oxo-2’-脱氧鸟苷（OXO）表达、谷胱甘肽过氧化物酶（GPX）和谷胱甘肽还原酶（GR） mRNA及其他氧化应激和抗氧化标志物水平。效应量（ES）用于评估组间差异。结果与KET组相比，MICT显著减少凋亡细胞（ES = 14.24, p < 0.0001），降低Bax和caspase-3蛋白表达，升高Bcl-2 (ES = 2.77, p = 0.005；caspase-3: ES = 7.73, p < 0.0001；Bcl-2: ES = 12.11, p < 0.001)。Bax和caspase-3 mRNA表达降低(Bax: ES = 4, p = 0.014；caspase-3: ES = 2.29, p = 0.024)。MICT降低了OXO，增加了GR和GPX mRNA和一氧化氮（NO）水平(GR: ES = 2.02, p = 0.016；GPX: ES = 1.98, p = 0.035；OXO: ES = 11.39, p < 0.0001；NO: ES = 3.52, p = 0.003)。丙二醛、髓过氧化物酶、谷胱甘肽、超氧化物歧化酶和过氧化氢酶的水平在两组之间保持不变。结论MICT可有效减少长期氯胺酮滥用大鼠大脑皮层的细胞凋亡和氧化损伤。

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来源期刊

Addiction Biology 生物-生化与分子生物学

CiteScore

8.10

自引率

2.90%

发文量

118

审稿时长

6-12 weeks

期刊介绍： Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields. Addiction Biology includes peer-reviewed original research reports and reviews. Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.