B79-18 Lysyl Oxidase Family Activity in Experimental Interstitial Pneumonia and Pharmacologic Modulation by Ecdisten, Acetylcysteine, and Polyoxidonium

Abstract Rationale Lysyl oxidase (LOX) and LOX-like isoenzymes (LOXL1-4) drive collagen/elastin cross-linking and matrix remodeling, central to pulmonary fibrosis. We assessed how interstitial pneumonia (IP) alters LOX/LOXL activities in blood and lung tissue, and whether antioxidant/immunomodulatory regimens attenuate this signal. Methods White rats (150–200 g) were exposed to chronic tobacco smoke for two months to induce IP, then randomized (n = 8/group) to: intact; IP control; ecdisten; acetylcysteine (ACC); polyoxidonium; ecdisten+ACC; ecdisten+polyoxidonium; ecdisten+ACC+polyoxidonium. Treatments were given per os once daily for 15 days. After sacrifice, serum and lung homogenates were analyzed for LOX-1/2/3/4 by ELISA (Quantikine/R&D Systems). Group comparisons used percentage change vs IP control and vs intact. Results Baseline/IP effect. Versus intact animals, IP increased serum LOX-1/2/3/4 ≈2.7–2.8-fold (e.g., LOX-1: 15.3±0.49 vs 5.6±0.18 ng/mL; LOX-3: 16.5±0.53 vs 6.1±0.19 ng/mL). Lung tissue showed similar rises ≈2.7–2.8-fold (e.g., LOX-1: 18.1±0.58 vs 6.4±0.20 ng/mg protein; LOX-3: 19.4±0.62 vs 7.0±0.22). These patterns indicate strong fibrotic/remodeling activation. Monotherapies. Versus IP control, ecdisten reduced serum LOX-1/2/3/4 by ∼20–26% (e.g., LOX-1 11.4±0.36; LOX-4 11.2±0.36 ng/mL). ACC achieved smaller reductions (∼11–16%). Polyoxidonium produced the largest monotherapy effect (∼28–33% serum reduction; e.g., LOX-1 10.2±0.32; LOX-3 11.8±0.38 ng/mL). Lung homogenate results paralleled serum (ecdisten ∼20–25%, ACC ∼10–15%, polyoxidonium ∼30–34% lower vs IP control). Combinations Dual regimens amplified effects: ecdisten+ACC lowered serum LOX-1/2/3/4 by ∼41–43%; ecdisten+polyoxidonium by ∼47–48%. The triple therapy (ecdisten+ACC+polyoxidonium) produced the most pronounced attenuation (∼56–60% vs IP control), bringing both serum and lung LOX values close to intact (e.g., lung LOX-1 7.3±0.23 vs intact 6.4±0.20 ng/mg). Conclusions Experimental IP robustly upregulates LOX-1/2/3/4 in blood and lung, consistent with active fibrotic remodeling. Pharmacologic modulation—especially triple therapy with ecdisten+ACC+polyoxidonium—substantially suppresses LOX/LOXL activity toward intact levels. These findings support LOX/LOXL enzymes as measurable biomarkers and therapeutic targets for anti-fibrotic strategies and justify translational evaluation in ILD cohorts. This abstract is funded by: None

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