Abstract
The aim of the present study was to evaluate the anti-glioma activity of 3-(4-fluorobenzyl)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (AV23) in a preclinical model of glioblastoma, as well as behavioral parameters and toxicological profile. The implantation of C6 cells in the left striatum of male Wistar rats was performed by stereotaxic surgery. After recovery, animals were treated with vehicle (canola oil) or AV23 (10 mg/kg/day) intragastrically for 15 days. It was found that AV23 reduced tumor volume by 90%. Serum biochemical parameters such as triglycerides, cholesterol, HDL-cholesterol, LDL-cholesterol, albumin, aspartate aminotransferase, urea, creatinine and total proteins were not changed; however, there was a slight increase in alanine aminotransferase. The compound AV23 reverted the hypoglycemia and the reduction in body weight caused by glioblastoma. Additionally, AV23 was able to revert the reduction of locomotion caused by the tumor implantation. Therefore, the compound AV23 can be considered a promising candidate in the treatment of glioblastoma.
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Funding
This study was financed by Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS − 17/2551-0000988-6) and in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. W.C., F.M.S and R.M.S. are recipient of the CNPq fellowship.
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Alana de Vasconcelos: AV23 synthesis, animal’s treatment, statistical analysis, manuscript preparation. Larissa Ribeiro de Moura: AV23 synthesis. Nathalia Stark Pedra: C6 cells culture, animal’s treatment, biochemical analysis, tumor quantification. Natália Pontes Bona: C6 cells culture, glioma implantation, animal’s treatment, biochemical and behavioral analysis, tumor quantification, statistical analysis. Mayara Sandrielly Pereira Soares: Glioma implantation, animal’s treatment. Magno da Silva Marques: Histological analysis. Ana Paula Horn: Histological analysis. Luiza Spohr: Glioma implantation, animal’s treatment, behavioral analysis. Roselia Maria Spanevello: Experimental design, results interpretation, discussion, and manuscript preparation. Francieli Moro Stefanello: Experimental design, results interpretation, discussion, and manuscript preparation. Wilson Cunico: Experimental design, results interpretation, discussion, and manuscript preparation.
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All procedures involving animal models were approved by the Animal Ethics and Experimentation Committee of the Federal University of Pelotas (UFPel) under protocol number CEEA (9219). The protocols complied with the Brazilian Guidelines for the Care and Use of Animals in Scientific Research Activities (DBCA), which is in accordance with the expectations described by the National Council for the Control of Animal Experimentation (CONCEA).
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de Vasconcelos, A., de Moura, L.R., Pedra, N.S. et al. Thiazolidine-2,4-dione derivative exhibits antitumoral effect and reverts behavioral and metabolic changes in a model of glioblastoma. Metab Brain Dis 37, 2053–2059 (2022). https://doi.org/10.1007/s11011-022-01005-5
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DOI: https://doi.org/10.1007/s11011-022-01005-5