Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Rigalli, Juan Pablo [VerfasserIn]   i
Titel:The trypanocidal benznidazole promotes adaptive response to oxidative injury
Titelzusatz:involvement of the nuclear factor-erythroid 2-related factor-2 (Nrf2) and multidrug resistance associated protein 2 (MRP2)
Verf.angabe:Juan Pablo Rigalli, Virginia Gabriela Perdomo, Nadia Ciriaci, Daniel Eleazar Antonio Francés, María Teresa Ronco, Amy Michele Bataille, Carolina Inés Ghanem, María Laura Ruiz, José Enrique Manautou, Viviana Alicia Catania
E-Jahr:2016
Jahr:12 May 2016
Umfang:9 S.
Fussnoten:Gesehen am 21.10.2021
Titel Quelle:Enthalten in: Toxicology and applied pharmacology
Ort Quelle:Orlando, Fla. : Academic Press, 1959
Jahr Quelle:2016
Band/Heft Quelle:304(2016), Seite 90-98
ISSN Quelle:1096-0333
Abstract:Oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. Benznidazole (BZL) is the only trypanocidal agent available for treatment of Chagas disease in endemic areas. Its use is associated with side effects, including increases in biomarkers of hepatotoxicity. However, BZL potential to cause oxidative stress has been poorly investigated. Here, we evaluated the effect of a pharmacologically relevant BZL concentration (200μM) at different time points on redox status and the counteracting mechanisms in the human hepatic cell line HepG2. BZL increased reactive oxygen species (ROS) after 1 and 3h of exposure, returning to normality at 24h. Additionally, BZL increased glutathione peroxidase activity at 12h and the oxidized glutathione/total glutathione (GSSG/GSSG+GSH) ratio that reached a peak at 24h. Thus, an enhanced detoxification of peroxide and GSSG formation could account for ROS normalization. GSSG/GSSG+GSH returned to control values at 48h. Expression of the multidrug resistance-associated protein 2 (MRP2) and GSSG efflux via MRP2 were induced by BZL at 24 and 48h, explaining normalization of GSSG/GSSG+GSH. BZL activated the nuclear erythroid 2-related factor 2 (Nrf2), already shown to modulate MRP2 expression in response to oxidative stress. Nrf2 participation was confirmed using Nrf2-knockout mice in which MRP2 mRNA expression was not affected by BZL. In summary, we demonstrated a ROS increase by BZL in HepG2 cells and a glutathione peroxidase- and MRP2 driven counteracting mechanism, being Nrf2 a key modulator of this response. Our results could explain hepatic alterations associated with BZL therapy.
DOI:doi:10.1016/j.taap.2016.05.007
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1016/j.taap.2016.05.007
 Volltext: http://www.sciencedirect.com/science/article/pii/S0041008X16301132
 DOI: https://doi.org/10.1016/j.taap.2016.05.007
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Benznidazole
 Multidrug resistance associated protein 2
 Nuclear factor-erythroid 2-related factor-2
 Oxidative stress
K10plus-PPN:1745147004
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68682329   QR-Code
zum Seitenanfang