Turkkan O Kaygusuz, Besir Er, Ramazan Ozmen, James R Komorowski, Kazim Sahin
Low-dose LPS was associated with coordinated disturbances in brain NAD-related metabolism, redox balance, and inflammatory signaling. The combined intervention produced a broader biochemical and molecular response than the single interventions; however, mechanistic, histological, behavioral, and translational studies are required before clinical relevance can be inferred.
BACKGROUND: Systemic lipopolysaccharide (LPS)-induced inflammation can disrupt cerebral redox homeostasis and nicotinamide adenine dinucleotide (NAD)-related metabolism, but the extent to which a multimodal nutritional intervention can attenuate these changes remains unclear.
OBJECTIVE: This study compared the effects of phycocyanin-derived oligopeptides (PC-O), zinc (Zn), selenium (Se), and their combined administration on whole-brain NAD-related metabolites, oxidative status, antioxidant enzyme activities, selected mRNA markers, and the protein abundance of representative neurotrophic, synaptic, astroglial, and inflammatory markers after low-dose LPS exposure.
METHODS: Forty-two male BALB/c mice were allocated to six groups (n = 7/group). PC-O, Zn, Se, or PC-O + Zn + Se was administered orally for 14 days before intraperitoneal LPS challenge (0.04 mg/kg).
RESULTS: LPS was associated with lower concentrations of the four NAD-related analytes and lower antioxidant enzyme activities, higher MDA, reduced BDNF, NGF, Synapsin-1, PGC-1α, and TFAM transcripts, and increased GFAP, IL-1β, and IL-6 transcripts (p < 0.05). Western blot analysis further showed lower BDNF and Synapsin I protein abundance and higher GFAP, IL-1β, and IL-6 protein abundance following LPS exposure (p < 0.05). The single-supplements produced endpoint-dependent changes, whereas the PC-O + Zn + Se group showed the most consistent attenuation across the biochemical, transcript, and selected protein outcomes.
CONCLUSION: Low-dose LPS was associated with coordinated disturbances in brain NAD-related metabolism, redox balance, and inflammatory signaling. The combined intervention produced a broader biochemical and molecular response than the single interventions; however, mechanistic, histological, behavioral, and translational studies are required before clinical relevance can be inferred.