Therapeutic efficacy to dose-dependent toxicity of Cabazitaxel in C6-induced glioblastoma model of rats.

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.