Insights of In-silico Neurotoxicity Studies of Glucuronolactone, Taurine and Gluconolactone Correlating the Induced Neuronal Alteration in Rat Pups

Abstract

Background: Signifi cant concentrations of food additives found in energy drinks have the potential to be neurotoxic and promote oxidative stress, among other negative consequences. Pregnant rats were split up into six groups for the current study. Group 1 received vehicle, CAF standard (25 mg/kg p.o.), groups 3-6 received GLUR (5 mg/kg p.o.), TAU (8 mg/kg p.o.), GLU (84 mg/kg p.o.), and combinations of the three chosen food additives (CF), respectively. From prenatal day 3 through postnatal day 15, certain food additives were administered to pregnant rats at signifi cant doses. After parturition on PND 21, behavioral changes were assessed using the Rotarod, active avoidance, and elevated plus maze tests. On PND 30, 45, and 60, rat brain tissue had its acetylcholine and epinephrine levels evaluated. Further, on days 30 and 60, brain tissue was assessed for the presence of oxidative stress markers such as lipid peroxidation, catalase, superoxide dismutase, and glutathione peroxidase. Finally, histopathological studies were carried out in brain hippocampal region. Further in-silico studies were carried out on selected receptors. Results: Rat pups fed with food additives showed a signifi cant (p &lt 0.001) change in behavior, including memory, cognition, and motor activity. Increased lipid peroxidation and decreased anti-oxidant enzymes were signifi cant in TAU and CF groups. Further in-silico studies were carried out, where GLUR showed high binding affi nity to specifi c receptor targets, GABA A and NMDA1 receptors, and specifi c enzyme targets MAO A and MAO B neurotransmitter metabolic enzymes compared to caff eine hinted the decrease in neurotransmitters as in-vivo studies. Conclusion: The current fi ndings support the hypothesis that the chosen dose and mix of food additives altered rat pups’ neurobehavioral and neurotransmitter profi les.