Toxicological Screening of Four Bioactive Citroflavonoids: In Vitro, In Vivo, and In Silico Approaches

Molecules

Emanuel Hernández-Núñez¹  ÁngelJosabad Alonso-Castro²  AvelAdolfo González-Sánchez³  M.A. Lucio-Garcia⁴  JesúsAlfredo Araujo-León⁴  TaniaIsolina Coral-Martínez⁴  JuanCarlos Sánchez-Salgado⁵  Amanda Sánchez-Recillas⁶  Victor Yáñez-Pérez⁶  Rolffy Ortiz-Andrade⁶  Gabriel Navarrete-Vazquez⁷  Irma Aranda-González⁸  Sergio Hidalgo-Figueroa⁹ 

[1] Departamento de Recursos del Mar, Centro de Investigación y de Estudios Avanzados del Istituto Politécnico Nacional-Unidad Mérida, Merida 97205, Yucatan, Mexico;División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato 36050, Guanajuato, Mexico;Facultad de Ingeniería, Universidad Autónoma de Yucatán, Merida 92203, Yucatan, Mexico;Grupo de Investigación en Química Analítica y Ambiental, Facultad de Química, Universidad Autónoma de Yucatán, Merida 97069, Yucatan, Mexico;Hypermedic MX, Hacienda Santa Cecilia 97, Cafetales I, Coyoacán 04930, Mexico City, Mexico;Laboratorio de Farmacología, Facultad de Química, Universidad Autónoma de Yucatán, Merida 97069, Yucatan, Mexico;Laboratorio de Química Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico;Licenciatura en Nutrición, Facultad de Medicina, Universidad Autónoma de Yucatán, Merida 97000, Yucatan, Mexico;Research, Innovation and Development Consortium for Arid Areas, Potosino Institute of Scientific and Technological Research, San Luis Potosi 78216, San Luis Potosi, Mexico;

关键词: citroflavonoids;    low-risk substances;    acute oral toxicity;    MTT-based assay;    toxicity prediction;   

DOI  :  10.3390/molecules25245959

来源: DOAJ

【 摘 要 】

Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC₅₀ of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD₅₀ value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD⁵⁰ was LD₅₀ > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.

【 授权许可】

Unknown