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Effect of vitamin E on doxorubicin and paclitaxel-induced memory impairments in male rats

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Abstract

Purpose

In addition to peripheral neuronal dysfunction, conventional chemotherapy can be associated with other neurological treatment-limiting adverse effects, including cognitive dysfunction, memory impairment, and anxiety, which are referred to as “chemobrain”. This study aimed to investigate the effects of doxorubicin (DOX) and paclitaxel (PAC) on learning and memory in rats using radial arm water maze (RAWM) and investigated a potential beneficial effect of vitamin E (Vit. E).

Methods

Adult male rats were injected with four doses of 2 mg/kg/week DOX, or 2 mg/kg PAC every other day intraperitoneally. Vit. E was co-administered with these drugs in other groups to study its antioxidative effects. Using the RAWM, each rat was assessed for learning and memory performance through two sets of six trials separated by a 5-min rest period evaluating both short- and long-term effects on memory.

Results

There was no deficit in learning or long-term memory in both drug groups compared to control. However, rats in both drug groups made significantly more errors in all short-term memory trials. This effect was mitigated when Vit. E was co-administered with either drug. Moreover, PAC (but not DOX) induced hippocampal lipid peroxidation by increasing the levels of standard biomarker thiobarbituric acid reactive substances (TBARS). Interestingly, Vit. E prevented PAC-induced hippocampal oxidative stress. Furthermore, both DOX and PAC were correlated with reduction in Brain-Derived Neurotrophic Factor (BDNF) expression levels in the hippocampus, which was overcome by the co-administration of Vit. E.

Conclusion

There is a potential role of Vit. E in alleviating short-term memory impairment in rats exposed to chemotherapy, possibly by reducing hippocampal oxidative stress and neurodegeneration.

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Data availability

The data that support the findings of this study are not openly available due to logistic reasons. However, they will be available upon reasonable request. Data archiving is not mandated.

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Acknowledgements

This work was supported by Deanship of Research in Jordan University of Science and Technology (grant #: 109/2021). Also, the authors would like to thank Khawla Al-Mhedat and Roaa Obiedat for their technical support.

Funding

This project was funded by the Deanship of Research, Jordan University of Science and Technology (Grant number: 109/2021).

Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan

    Ahmad A. Altarifi, Kareem Sawali & Malik Abu Al-Rub

  2. Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab Emirates

    Karem H. Alzoubi

  3. Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

    Karem H. Alzoubi

  4. Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, Jordan

    Tareq Saleh

  5. Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan

    Omar Khabour

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  1. Ahmad A. Altarifi
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Correspondence to Ahmad A. Altarifi.

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Altarifi, A.A., Sawali, K., Alzoubi, K.H. et al. Effect of vitamin E on doxorubicin and paclitaxel-induced memory impairments in male rats. Cancer Chemother Pharmacol 93, 215–224 (2024). https://doi.org/10.1007/s00280-023-04602-y

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