Caffeic acid and quercetin exert caspases-independent apoptotic effects on Leishmania major promastigotes, and reactivate the death of infected phagocytes derived from BALB/c mice
10.1016/j.apjtb.2017.01.022
- Author:
Radia BELKHELFA-SLIMANI
1
;
Bahia DJERDJOURI
1
Author Information
1. Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene
- Publication Type:Journal Article
- Keywords:
Apoptosis;
iNOS;
Leishmania major;
NF-κB;
Phagocytes;
TNF-α
- From:Asian Pacific Journal of Tropical Biomedicine
2017;7(4):321-331
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the leishmanicidal effects of two antioxidants, caffeic acid and quercetin on Leishmania major (L. major) promastigotes in vitro, and their immuno-modulatory effects on infected phagocytes derived from susceptible BALB/c mice. Methods Caffeic acid and quercetin-induced cell death was examined by Pi-Hoechst double staining of L. major promastigotes and MTT assay, in the presence or absence of protease inhibitors in vitro. Caffeic acid or quercetin were administered subcutaneously to BALB/c mice infected with L. major promastigotes through a dorsal air pouch. Nitric oxide and superoxide anion production by phagocytes infiltrating the air pouch and the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B in the air pouch membrane were therefore evaluated using appropriate methods. Results Caffeic acid and quercetin displayed a dose-dependent cytotoxic effect against L. major promastigotes, and induced cell death via caspases-independent pathways. In vivo, L. major promastigotes inoculation into air pouch cavity of BALB/c mice leads to a sequential influx of neutrophils (hours), followed by macrophages (days). Results showed that L. major delayed apoptosis of infected neutrophils and macrophages by the cleavage of the nuclear factor kappa B p65
