Curcumin-loaded nanocapsules attenuate LPS-induced toxicity in Drosophila melanogaster and modulate Nrf2 and p38 MAPK signaling

Some diseases and toxic agents induce oxidative stress and inflammatory processes. In this context, curcumin has attracted attention because of its antioxidant properties, although its therapeutic application is limited by factors such as poor bioavailability. Nanoparticle-based delivery systems have been proposed as an approach to improve the biological availability of curcumin. The present study investigated whether curcumin-loaded nanocapsules attenuate lipopolysaccharide (LPS)-induced toxicity in Drosophila melanogaster, with particular emphasis on oxidative stress, antioxidant defenses, and stress-related signaling pathways. Fifty flies of both sexes were divided into four groups: control, LPS (250 µg/kg diet), curcumin-loaded nanocapsules (10 µM), and LPS plus curcumin-loaded nanocapsules. After the treatment period, survival, locomotor and exploratory behaviors, oxidative stress parameters, antioxidant enzyme activities, Nrf2 immunoreactivity, p38 MAPK phosphorylation, and cellular metabolic capacity were evaluated. LPS exposure decreased survival and locomotor performance, increased reactive species and lipid peroxidation, decreased GST, SOD, and CAT activities, reduced Nrf2 immunoreactivity, increased phospho-p38 MAPK and the phospho-p38 MAPK/p38 MAPK ratio, and decreased cellular metabolic capacity. Co-exposure with curcumin-loaded nanocapsules attenuated these LPS-induced alterations. These protective effects were accompanied by restoration of Nrf2 immunoreactivity and reduction of phospho-p38 MAPK signaling. These findings indicate that curcumin-loaded nanocapsules attenuate LPS-induced toxicity in Drosophila melanogaster, and suggest that their protective effects are associated with improved redox homeostasis, antioxidant defenses, cellular function, and modulation of Nrf2 and p38 MAPK signaling.