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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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.