Assessment of cytotoxicity, genotoxicity, and mutagenicity of the dexchlorpheniramine reference standard and pharmaceutical formula in human peripheral blood mononuclear cells

Abstract Dexchlorpheniramine is a first-generation classical antihistamine, clinically used to treat allergies. The main objective of our study was to evaluate the effects of the dexchlorpheniramine reference standard (DCPA Ref. St) and a pharmaceutical formula on DNA in human peripheral blood mononuclear cells (PBMCs). We exposed PBMCs to five different concentrations (0.5, 2.5, 5, 10, and 50 ng/mL) of DCPA Ref. St DCPA Ref. St and pharmaceutical formula in order to evaluate their cytotoxic, genotoxic, and mutagenic potential. The results showed that both dexchlorpheniramine formulations did not affect PBMC viability and CD3+, CD4+, or CD8+ lymphocyte subpopulations. The DCPA Ref. St and pharmaceutical formula neither induced genotoxic or mutagenic effects nor numerical or structural chromosomal alterations in PBMCs after 24 hours of exposure.

CdCl2 has zero-order kinetic cellular influx and induces cytotoxicity and genotoxicity at low concentrations in human leukocytes in vitro / El CdCl2 tiene un influjo celular cinético de orden cero e induce citotoxicidad y genotoxicidad a bajas concentraciones en leucocitos humanos in vitro

SUMMARY Cadmium (Cd2+) is a nonessential heavy metal that possesses a high capacity of bioaccumulation and exhibits toxic characteristics even at low concentrations. This study evaluated the genotoxicity and cytotoxicity in human leukocytes in vitro after exposure to a lower range of Cd2+concentration (1-25 (g/mL) using an unprecedented strategy by correlating between intracellular Cd2+ levels after exposure and cellular damage. Results demonstrated that Cd2+exposure from 5 to 25 fig/mL significantly increased the unviability of leukocytes, as well as the DNA damage, which was dose-dependent. The intracellular Cd2+ levels in leukocytes ranged from 9.85 to 94.38 pg/cell, and cytotoxicity and genotoxicity were induced at a concentration of24.22 pg/cell. The relationship between exposure concentration and intra-cellular Cd2+ levels suggests that its influx occurs in human leukocytes under zero-order kinetics.

RESUMEN El cadmio (Cd2+) es un metal pesado no esencial que posee una alta capacidad de bioacumulación y presenta características tóxicas incluso en bajas concentraciones. Este estudio evaluó la genotoxicidad y la citotoxicidad en leucocitos humanos in vitro después de la exposición a un rango inferior de concentración de Cd2+ (1-25 (g / mL) mediante una estrategia sin precedentes al correlacionar los niveles intracelulares de Cd2+ después de la exposición y el daño celular. Los resultados demostraron que la exposición a Cd2+ de 5 a 25 (g/mL aumentó significativamente la inviabilidad de los leucocitos, así como el daño en el ADN, que era dependiente de la dosis. Los niveles intracelulares de Cd2+ en leucocitos oscilaron entre 9,85 y 94,38 pg/célula, y se indujo la citotoxicidad y la genotoxicidad a una concentración de 24,22 pg/ célula. La relación entre la concentración de la exposición y los niveles intracelulares de Cd2+ sugiere que su influjo se produce en leucocitos humanos bajo una cinética de orden cero.