Potential of casein as a nutrient intervention to alleviate lead (Pb) acetate-mediated oxidative stress and neurotoxicity: First evidence in Drosophila melanogaster

Understanding the interaction between dietary protein deficits and neurotoxicants such as lead (Pb) is
critical since oxidative stress is a common denominator under such conditions. The Drosophila system is
an extensively used model to investigate the interaction between nutrients and environmental
toxicants. Accordingly, we have examined the hypothesis that casein (CSN) enrichment has the
propensity to attenuate Pb-associated phenotype, oxidative stress and neurotoxicity in Drosophila
melanogaster. Exposure of young (2–3 d) and adult flies (10–12 d old) to Pb acetate (0–20 mM, 7 d) in
the medium resulted in a concentration dependent mortality and the survivors exhibited a hyperactive
phenotype. While males showed higher susceptibility to Pb among both age groups, young flies were
relatively more susceptible than adults. Pb exposure (5–10 mM, 5 d) among young flies caused robust
oxidative stress as evidenced by markedly elevated levels of reactive oxygen species with concomitant
perturbations in the activities of antioxidant enzymes (diminished SOD and elevated thioredoxin
reductase) and altered redox state. Further, Pb caused significant elevation in the activity of
acetylcholinesterase and dopamine levels. In a satellite study, we assessed the modulatory effect of
CSN-enriched diet (1–2%) on Pb intoxication in terms of lethality, hyperactivity, oxidative stress and
neurotoxicity. CSN markedly offset Pb-induced lethality and diminished the hyperactivity response.
While CSN enrichment among Pb (5 mM) treated flies caused further elevation in ROS levels and
thioredoxin reductase activity, the SOD levels were restored to normalcy. Further, CSN improved the
activity levels of complex I–III and restored the dopamine levels. Our data suggest that Pb-induced
toxicity in the Drosophila system may be predominantly mediated through oxidative stress mechanisms
and the propensity of casein-enriched diet to abrogate such responses. Hence, we propose that
enrichment of diet with protein such as casein may be a useful approach to alleviate Pb associated
adverse effects in children.