Evidence of acrylamide induced oxidative stress and neurotoxicity in Drosophila melanogaster – Its amelioration with spice active enrichment: Relevance to neuropathy

Acrylamide (ACR) intoxication in its monomeric form leads to neuronal damage in both experimental
animals and humans. Oxidative stress is one of the principle mechanisms related to the neurotoxicity of
ACR exposure. Hence, the present study aimed to recapitulate the potential of ACR to cause oxidative
stress and neurotoxic effects in Drosophila melanogaster. Exposure of adult male flies (Oregon K strain)
to ACR (1–10 mM, 7 d) in the diet resulted in a concentration and time dependent mortality, while the
survivors exhibited significant locomotor deficits. Further, ACR exposure (1–5 mM, 3 d) caused robust
oxidative stress as evidenced by markedly elevated levels of reactive oxygen species and
hypdroperoxides in head/body regions. Enhanced lipid peroxidation, perturbations in the activities
of antioxidant enzymes accompanied with depletion of reduced glutathione levels in head region at
high concentrations suggested induction of oxidative stress. Further, marked diminution in the
activities of complexes I–III, Succinic dehydrogenase, with concomitant reduction in MTT suggested the
propensity of ACR to impair mitochondrial function. Furthermore, ACR-induced neurotoxic effects were
discernible in terms of diminished ATPase activity, enhanced activity of acetylcholinesterase and
dopamine depletion. In a satellite study, employing a co-exposure paradigm, we tested the propensity
of spice actives namely eugenol (EU) and isoeugenol (IE) to ameliorate ACR-induced neurotoxicity. EU/
IE enriched diet offered marked protection against ACR-induced mortality, locomotor dysfunctions and
oxidative stress. Furthermore, the spice actives prevented the depletion of reduced GSH levels,
maintained the activity of AChE enzyme and dopamine levels in head region. Collectively, these findings
clearly demonstrate that ACR induced neurotoxicity in Drosophila may be mediated through oxidative
stress mechanisms and the potential of spice actives to abrogate the condition. These data suggest that
Drosophila may serve as a suitable model to understand the possible mechanism/s associated with ACR
associated neuropathy.