Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster

Abstract

Dichloroacetic acid (DCA), a water disinfection by-product, has attained emphasis due to its prospect for clinical use against different diseases including cancer along with negative impact on organisms. However, these reports are based on the toxicological as well clinical data using comparatively higher concentrations of DCA without much of environmental relevance. Here, we evaluate cellular as well as organismal effects of DCA at environmentally and mild clinically relevant concentrations (0.02-20.0 μg/ml) using an established model organism, Drosophila melanogaster. Flies were fed on food mixed with test concentrations of DCA for 12-48 h to examine the induction of reactive oxygen species (ROS) generation, oxidative stress (OS), heat shock genes (hsps) and cell death along with organismal responses. We also examined locomotor performance, ROS generation, glutathione (GSH) depletion, expression of GSH-synthesizing genes (gclc and gclm), and hsps at different days (0, 10, 20, 30, 40, 50) of the age in flies after prolonged DCA exposure. We observed mild OS and induction of antioxidant defense system in 20.0 μg/ml DCA-exposed organism after 24 h. After prolonged exposure to DCA, exposed organism exhibited improved survival, elevated expression of hsp27, gclc, and gclm concomitant with lower ROS generation and GSH depletion and improved locomotor performance. Conversely, hsp27 knockdown flies exhibited reversal of the above end points. The study provides evidence for the attenuation of cellular and functional decline in aged Drosophila after prolonged DCA exposure and the effect of hsp27 modulation which further incites studies towards the therapeutic application of DCA.

Agar-polydimethylsiloxane devices for quantitative investigation of oviposition behaviour of adult Drosophila melanogaster

“…7 It is employed in chemical screening and toxicology studies whereby behaviours, such as oviposition, 8 movement, 9 foraging, 10 avoidance, 11 and mating, 12 are assayed in response to environmental toxicants. 1,[12][13][14] Oviposition is the process of egg-laying in D. melanogaster that is dependent on responses of the fly to environmental stimuli (such as chemicals, physical conditions of the substrate, temperature, light, population density, and humidity). [15][16][17][18][19] D. melanogaster possesses sensory neurons (such as taste 20,21 and touch 22,23 sensing systems) to detect various environmental cues prior to selecting preferred sites for oviposition and egg laying.…”

Coupling Mechanism of Electromagnetic Field and Thermal Stress on Drosophila melanogaster

“…ROS level was detected through DCF fluorescence [ 23 ]. The supernatant (5 μl) was loaded with 295 μl of DCFH2-DA with a final concentration of 10 μM and then incubated at 37°C for 40 min.…”

BK channels and a cGMP-dependent protein kinase (PKG) function through independent mechanisms to regulate the tolerance of synaptic transmission to acute oxidative stress at theDrosophilalarval neuromuscular junction

“…A previous publication similarly utilized DCA to activate voltage-gated K þ channels in Drosophila (Dawson-Scully et al, 2010); however, this study did not directly demonstrate DCA activation of voltage-gated K þ channels in neurons or muscles. Recently, it has been shown that mature flies fed DCA display acute increases in ROS production and oxidative stress (Pandey et al, 2014). Therefore, the DCA-induced decrease in time to synaptic failure in Slo 4 mutants could potentially be attributed to DCA activating K þ channels, exacerbating oxidative stress, or modulating other metabolic processes.…”