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Therapeutic Efficacy to Dose-Dependent Toxicity of Cabazitaxel in C6-Induced Glioblastoma Model of Rats Publisher



Mohammadzadeh Z1 ; Khaksari M2 ; Nematollahi MH3 ; Kheirandish R4 ; Moslemizadeh A5 ; Delshad S4 ; Faramarz S6 ; Tezerji SS7 ; Torkashvand M8 ; Shahba S9 ; Bashiri H10
Authors
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Authors Affiliations
  1. 1. Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Haft-Bagh Highway, P.O. Box 76169 13555, Kerman, Iran
  2. 2. Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Haft-Bagh Highway, P.O. Box 76169 13555, Kerman, Iran
  3. 3. Physiology Research Center, Afzalipour School of Medicine, Kerman University of Medical Sciences, Haft-Bagh Highway, P.O. Box 76169 13555, Kerman, Iran
  4. 4. Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Imam Khomeni Highway, P.O. Box 76169 13439, Kerman, Iran
  5. 5. Department of Immunology, Tehran University of Medical Sciences, Dameshgh St., Vali-e Asr Ave., P.O. Box 14167 53955, Tehran, Iran
  6. 6. Department of Biochemistry, Kerman University of Medical Sciences, Haft-Bagh Highway, P.O. Box 76169 13555, Kerman, Iran
  7. 7. Department of Behavioural and Molecular Neurobiology, Regensburg Center for Neuroscience, University of Regensburg, Universitatsstraβe 31, 93053, Regensburg, Germany
  8. 8. College of Engineering, University of Tehran, Dameshgh St., Vali-e Asr Ave., P.O. Box 14167 53955, Tehran, Iran
  9. 9. Department of Biotechnology, School of Medicine, Semnan University of Medical Sciences, Bassij Blvd, P.O. Box 35147-99442, Semnan, Iran
  10. 10. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Haft-Bagh Highway, P.O. Box 76169 13555, Kerman, Iran

Source: Toxicology Research Published:2025


Abstract

This study was designed to adjust effective chemotherapy doses of cabazitaxel (CBZ) on cognitive behaviors, inflammatory cytokines and oxidative stress parameters, and survival rate in C6-induced GBM of rats. Male Sprague-Dawley rats bearing intra-caudate nucleus (CN) C6 inoculation were randomly divided into nine groups as follows: sham, tumor, Temozolomide (TMZ) vehicle, TMZ, CBZ vehicle, CBZ at doses of 0.5, 1, 2 and 4 mg/kg. Behavioral tests survival rate, histopathology, immunohistochemistry, oxidative stress, and inflammatory cytokines were evaluated. All drug treatments reduced the volume and number of tumor cells dose-dependently and CBZ4 was able to cause the greatest reduction. The %Survival rate of animals using CBZ1 significantly increased compared to other treatment groups. CBZ1 reduced anxiety-like behaviors and increased the balance of the animal with GBM. CBZ1 and CBZ2 groups improved C6-induced learning disabilities. Treatments could ameliorate tumor-induced dysregulation of oxidative stress. TNF-α/IL-10 decreased in the CBZ1 group compared to other treatment groups, which may indicate an improvement in inflammatory balance. Our findings demonstrate that the administration of CBZ at a dosage of 1 mg/kg exerts advantageous impacts on both the survival rate and neurocognitive performance of rats within the GBM model. However, our results showed that CBZ may have toxic effects, especially in a dose of 4 mg/kg. © 2025 The Author(s). Published by Oxford University Press. All rights reserved.
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