The Effects of Moderate-Intensity Continuous Training (MICT) and Berberine Supplementation (BB) on Ketamine-Induction Ferroptosis in Testicular Tissue of Wistar Rats: Emphasis on the Xc/GSH/GPX Signaling Pathway

Document Type : Original Article

Authors

Department of Exercise Physiology and Corrective Exercises, Faculty of Sport Sciences, Urmia University, Urmia, Iran

Abstract

Background and Purpose:  Long-term consumption of ketamine can result in adverse changes in biological tissues, including the testicles, as well as disruptions in the ferroptosis process. The primary strategy for addressing these effects involves discontinuing ketamine use and adopting nutritional interventions, supplementation, and exercise. Therefore, the present study aimed to investigate the effects of ketamine withdrawal, ketamine withdrawal combined with moderate-intensity continuous training (MICT), ketamine withdrawal accompanied by berberine supplementation (BB), and ketamine withdrawal combined with the MICT+BB on indices related to testicular ferroptosis in Wistar rats following chronic exposure to ketamine.
Materials and Methods: In this experimental study, 36 rats were randomly assigned to six groups, each consisting of six rats: 1) control, 2) ketamine, 3) ketamine withdrawal, 4) ketamine withdrawal + BB, 5) ketamine withdrawal + MICT, and 6) ketamine withdrawal + BB + MICT. Rats in the intervention groups were administered ketamine at a dose of 100 mg per kilogram of body weight for 8 weeks. Following this period, ketamine injection was stopped for all groups. Rats in the MICT groups exercised at an intensity equal to 65-70% of their maximum speed, while those in the BB supplementation groups received a dosage of 50 mg per kilogram of body weight for an additional 8 weeks. Levels of iron (Fe), glutathione (GSH), glutathione peroxidase (GPX), and malondialdehyde (MDA), as well as the expression of ferritin heavy chain (Fth), ferroportin (Fpn), iron-regulating transferrin receptor (Tfr1), and solute carrier family 7 member 11 (SLC7A11) were assessed. A one-way analysis of variance (ANOVA) was employed for between-group comparisons, and Tukey's post-hoc test was employed to identify differences among groups.
Results: Ketamine administration resulted in increased levels of Fe, MDA, and Tfr1, while GSH and GPX levels were decreased. In the ketamine withdrawal + BB and ketamine withdrawal + MICT groups, the levels of GPX, SLC7A11, GSH, and Fpn were significantly increased, whereas, MDA and Tfr1 were significantly reduced. Ultimately, the combined group (ketamine withdrawal + BB + MICT) exhibited the most substantial improvement in these indices (p < 0.05).
Conclusion: In summary, ketamine appears to increase oxidative stress and induce ferroptosis in the testicular tissue. Conversely, MICT and BB supplementation, both independently and synergistically can significantly ameliorate oxidative stress and the indices of testicular ferroptosis in male Wistar rats following chronic ketamine exposure. Overall, although both BB and MICT independently can effectively reduce the damage caused by oxidative stress and testicular ferroptosis, the results suggest that combination of MICT + BB has a  synergistic effect.
 

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References

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History

  • Receive Date: 05 September 2024
  • Revise Date: 18 October 2024
  • Accept Date: 10 November 2024
  • First Publish Date: 12 November 2024
  • Publish Date: 19 February 2025

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