title: Pharmacokinetic and Toxicological Evaluation of a Zinc Gluconate-Based Chemical Sterilant Using In Vitro and In Silico Approaches.
abstract: Sclerosing agents as zinc gluconate-based chemical sterilants (Infertile®) are used for chemical castration. This solution is injected into the animal testis, but there are not enough evidences of its safety profiles for the receivers. The present work aimed to establish the pharmacokinetics and toxicological activity of Infertile, using in vitro and in silico approaches. The evaluation at the endpoint showed effects in a dose-dependent manner. Since necrosis is potentially carcinogenic, the possible cell death mechanism could be apoptosis. Our data suggested that Infertile at 60 mM presented risk for animal health. Even though Infertile is a licensed product by the Brazilian Ministry of Agriculture, Livestock and Supply, it presented a high mutagenic potential. We suggest that the optimal dose must be less than 6 mM, once, at this concentration, no mutagenicity or genotoxicity was observed.
authors.affiliation: Department of Biophysics and Biometry, Rio de Janeiro State University, Boulevard 28 de Setembro, 87 Fundos, 4° Andar, 20551-030 Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Araujo-Lima
authors.affiliation: Department of Biophysics and Biometry, Rio de Janeiro State University, Boulevard 28 de Setembro, 87 Fundos, 4° Andar, 20551-030 Rio de Janeiro, RJ, Brazil.
authors.forename: Rafael J M
authors.initials: RJ
authors.lastname: Nunes
authors.affiliation: Department of Biophysics and Biometry, Rio de Janeiro State University, Boulevard 28 de Setembro, 87 Fundos, 4° Andar, 20551-030 Rio de Janeiro, RJ, Brazil.
authors.forename: Raphael M
authors.initials: RM
authors.lastname: Carpes
authors.affiliation: Department of Genetics and Molecular Biology, Federal University of the State of Rio de Janeiro, Rua Frei Caneca, 94 Centro, 20211-040 Rio de Janeiro, RJ, Brazil.
authors.forename: Claudia A F
authors.identifier: 0000-0003-4584-2757
authors.initials: CA
authors.lastname: Aiub
authors.affiliation: Department of Biophysics and Biometry, Rio de Janeiro State University, Boulevard 28 de Setembro, 87 Fundos, 4° Andar, 20551-030 Rio de Janeiro, RJ, Brazil.
authors.forename: Israel
authors.identifier: 0000-0003-1677-197X
authors.initials: I
authors.lastname: Felzenszwalb
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001938:Brazil; D002273:Carcinogens / Q000633:toxicity*; D002369:Castration / Q000379:methods; D003198:Computer Simulation; D005942:Gluconates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D000067996:RAW 264.7 Cells; D019779:Salmonella enterica / Q000737:chemistry / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology
chemical_list: D002273:Carcinogens; D005942:Gluconates; C030691:gluconic acid