Integrated Biomarker Response ranks the systemic oxidative burden of modified nucleoside analogues and quantifies quercetin-mediated redox recovery in LPS-induced endotoxemia in rats
DOI:
https://doi.org/10.22376/ijlpr.v16i3.2052Keywords:
Modified nucleosides, quercetin, oxidative stress, Integrated Biomarker Response, lipopolysaccharideAbstract
Modified nucleoside analogues are re-emerging as candidate antibacterial scaffolds, but their systemic redox cost under inflammation and the value of a dietary antioxidant co-treatment are poorly quantified. Eighty-five male Wistar rats were randomised into 17 groups (n = 5): naive control, LPS-only, LPS + quercetin, and seven analogues (2FaraA, 6ClAraPur, araCMP, TTU, FluMP, araC, cCMP) each with and without quercetin on a uniform LPS background. Six hepatic oxidative markers and eleven haematological markers were measured and compressed using the Integrated Biomarker Response (IBR), an Oxidative Stress Index (OSI), principal-component analysis (PCA) and ROC analysis. The analogues imposed a reproducible, rank-ordered oxidative burden: araC (IBR = 21.57) >cCMP (18.57) > 2FaraA (16.34) >FluMP (13.38) > TTU (12.74) > 6ClAraPur (11.43) >araCMP (11.30), all above LPS-only (7.70) and control (0.40). OSI mirrored IBR (Pearson r = 0.983). Quercetin restored the IBR toward control in every analogue, by 64.9–84.3 % (mean 74.4 %), with the largest rescue for araC, the most pro-oxidant member. PC1 captured 80.2 % of variance, ordering the groups along a single oxidative-burden axis. The antioxidant enzymes GPX, GSH and SOD (directed AUC 0.81–0.86) were most sensitive to quercetin, whereas serum AST was not (Kruskal–Wallis p = 0.73), indicating a redox-specific rather than a generalised hepatoprotective effect. These results establish a compact, integrative safety-screening framework that ranks modified nucleosides by systemic oxidative liability and demonstrates a consistent, class-independent quercetin redox rescue of approximately 74 %, offering a quantitative read-out for nucleoside-based antibacterial development.
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