Browsing by Author "Olivero-Verbel J."

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Ecotoxicological assessment of perchlorate using in vitro and in vivo assays
(Springer Verlag, 2018) Acevedo Barrios, Rosa; Sabater-Marco C.; Olivero-Verbel J.
Perchlorate is an inorganic ion widespread in the environment, generated as a natural and anthropogenic pollutant, with known endocrine disruption properties in the thyroid gland. Nonetheless, there are few reports of its ecotoxicological impact on wildlife. The aim of this study was to evaluate the adverse effects of KClO4 exposure on different cell lines, HEK, N2a, and 3T3, as well as in ecological models such as Vibrio fischeri, Pseudokirchneriella subcapitata, Daphnia magna, and Eisenia fetida. Perchlorate exhibited similar toxicity against tested cell lines, with LC50 values of 19, 15, and 19 mM for HEK, N2a, and 3T3, respectively; whereas in V. fischeri, the toxicity, examined as bioluminescence reduction, was considerably lower (EC50 = 715 mM). The survival of the freshwater algae P. subcapitata was significatively impaired by perchlorate (LC50 = 72 mM), and its effect on the lethality in the crustacean D. magna was prominent (LC50 = 5 mM). For the earthworm E. fetida, the LC50 was 56 mM in soil. In this organism, perchlorate induced avoidance behavior, weight loss, and decreased egg production and hatchling, as well as morphological and histopathological effects, such as malformations, dwarfism, and necrosis. In conclusion, perchlorate toxicity varies according to the species, although E. fetida is a sensitive model to generate information regarding the toxicological impact of KClO4 on biota. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
In silico drug repurposing for the identification of potential candidate molecules against arboviruses infection
(Elsevier B.V., 2020) Montes-Grajales D.; Puerta-Guardo H.; Espinosa D.A.; Harris E.; Caicedo-Torres W.; Olivero-Verbel J.; Martínez-Romero E.
Arboviral diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses represent a major public health problem worldwide, especially in tropical areas where millions of infections occur every year. The aim of this research was to identify candidate molecules for the treatment of these diseases among the drugs currently available in the market, through in silico screening and subsequent in vitro evaluation with cell culture models of DENV and ZIKV infections. Numerous pharmaceutical compounds from antibiotics to chemotherapeutic agents presented high in silico binding affinity for the viral proteins, including ergotamine, antrafenine, natamycin, pranlukast, nilotinib, itraconazole, conivaptan and novobiocin. These five last compounds were tested in vitro, being pranlukast the one that exhibited the best antiviral activity. Further in vitro assays for this compound showed a significant inhibitory effect on DENV and ZIKV infection of human monocytic cells and human hepatocytes (Huh-7 cells) with potential abrogation of virus entry. Finally, intrinsic fluorescence analyses suggest that pranlukast may have some level of interaction with three viral proteins of DENV: envelope, capsid, and NS1. Due to its promising results, suitable accessibility in the market and reduced restrictions compared to other pharmaceuticals; the anti-asthmatic pranlukast is proposed as a drug candidate against DENV, ZIKV, and CHIKV, supporting further in vitro and in vivo assessment of the potential of this and other lead compounds that exhibited good affinity scores in silico as therapeutic agents or scaffolds for the development of new drugs against arboviral diseases. © 2019 Elsevier B.V.