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    Cabazitaxel causes a dose-dependent central nervous system toxicity in rats
    (Elsevier, 2016) Karavelioglu, Ergun; Gonul, Yucel; Aksit, Hasan; Boyaci, Mehmet Gazi; Karademir, Mustafa; Simsek, Nejdet; Guven, Mustafa
    Background: Chemotherapeutic agents may lead to serious neurological side effects, which in turn can deteriorate the quality of life and cause dose limiting. Direct toxic effect or metabolic derangement of chemotherapeutic agents may cause these complications. Cabazitaxel is a next generation semi-synthetic taxane derivative, which is effective in both preclinical models of human tumors sensitive or resistant to chemotherapy and in patients with progressive prostate cancer despite docetaxel treatment. Aim: The primary aim of this study was to investigate the central nervous system toxicity of Cabazitaxel. Secondary aim was to investigate the safety dose of Cabazitaxel for the central nervous system. Methods: A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups as follows: group 1 (Controls), group 2 (Cabazitaxel 0.5 mg/kg), group 3 (Cabazitaxel 1.0 mg/kg) and group 4 (Cabazitaxel 1.5 mg/kg). Cabazitaxel (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to groups 2, 3 and 4 at 05, 1.0 and 1.5 mg/kg (body-weight/week) doses, respectively for four consecutive weeks. Beside this, group 1 received only i.p. saline at the same volume and time. At the end of the study, animals were sacrificed and bilateral brain hemispheres were removed for biochemical, histopathological and immunohistochemical examinations. Results: Intraperitoneal administration of Cabazitaxel has exerted neurotoxic effect on rat brain. We have observed that biochemical and immunohistochemical results became worse in a dose dependent manner. Conclusion: Our findings have suggested that Cabazitaxel may be a neurotoxic agent and can trigger apoptosis in neuron cells especially at high doses. (C) 2015 Elsevier B.V. All rights reserved.
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    Increased Expression of Matrix Metalloproteinases in Ligamentum Flavum Hypertrophy of the Patients with Lumbar Spinal Stenosis
    (Kamla-Raj Enterprises, 2016) Eser, Betul; Eser, Olcay; Simsek, Nejdet; Bulbul, Erdogan; Guven, Mustafa
    This paper shows an investigation of the expressions of MMP-3,-13 and their polymorphisms in patients with lumbar spinal stenosis (LSS). Hypertrophied LF tissues and peripheral bloods were obtained from 50 patients with LSS. The expressions of MMP-3,-13 and their polymorphisms were analyzed. No relationship was found between thickness of LFs and MMP-3,-13 genotypes. LF tissues were divided to three groups as grade 1, 2 and 3. Rich elastic fibrils were observed in grade 1. Elastic fibers and elastin/collagen rates decreased in grade 2-3 and 4, and collagen fibers increased and presented a cystic degeneration. MMP-3 immunopositive cells were higher than MMP-13. A correlation between LF thicknesses and MMP-3 was detected. Both MMP-3, -13 were expressed (MMP-3 in higher quantities) in high grade hypertrophied LF. The researchers expect that this paper would provide a better understanding of the pathogenesis of LF hypertrophy and lead to therapeutic alternatives for LSS patients.
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    Selenium protects cerebral cells by cisplatin induced neurotoxicity
    (Acta Cirurgica Brasileira, 2015) Karavelioglu, Ergun; Boyaci, Mehmet Gazi; Simsek, Nejdet; Sonmez, Mehmet Akif; Koc, Rabia; Karademir, Mustafa; Guven, Mustafa
    PURPOSE: To evaluate the central nervous system toxicity of cisplatin and neuroprotective effect of selenium. METHODS: Twenty-one male Wistar albino rats were divided into three groups: control (C), cisplatin (CS), cisplatin and selenium (CSE, n=7 in each group). Cisplatin (12 mg/kg/day, i.p.) was administered to CS and CSE groups for three days. Furthermore, CSE group received 3mg/kg/day (twice-a-day as 1.5 mg/kg) selenium via oral gavage five days before cisplatin injection and continued for 11 consecutive days. The same volumes of saline were administered to C group intraperitoneally and orally at same time. RESULTS: Heterochromatic and vacuolated neurons and dilated capillary vessels in the brain were observed in the histochemical examinations of cisplatin treated group. Rats that were given a dose of 3mg/kg/day selenium decreased the cisplatin induced histopathological changes in the brain, indicating a protective effect. In addition, cytoplasmic staining of the cell for bcl-2, both cytoplasmic and nuclear staining for bax were determined to be positive in the all groups. Bax positive cells were increased in the CS group compared to C group, in contrast to decreased bcl-2 positivity. CONCLUSION: Selenium limited apototic activity and histological changes due to the cisplatin related central neurotoxicity.