Table 1.
In vivo models of chronic lung diseases treated with modified or non-saccharide GAGs.
| Animal Model | Treatment (Dose and Administration) | Outcome Measures | Reference |
|---|---|---|---|
| Balb/c mice: NE airway inflammation model NE (o.a.) ± ODSH (o.a.) |
Days 1, 4, 7: NE (44 μM) or NS ODSH (635 μM) or NS o.a. Day 8: BAL/lung harvest |
NE induces BAL cells & PMN, KC, HMGB1 ODSH+NE: decreases total cells and PMN; decreases KC and HMGB1 |
Griffin et al. (2014) |
| C57BL/6 mice: P. aeruginosa (PA01) pneumonia model PA01 (i.n.) PA01 (i.t.) ± ODSH (s.c.) |
Day 1: PA01 i.n. ODSH (8.3- 75 mg/kg) or NS s.c. q 12 h x 2 Day 2: BAL/lung harvest Day 1: PA01 i.t. ODSH (75 mg/kg) or NS s.c. 12 h x 4 Day 3: survival |
ODSH decreases PA01 CFU; decreases lung protein content and edema; decreases total and PMN cell count; decreases BAL HMGB1; inhibits TLR2 and TLR4 binding ODSH improves mouse survival |
Sharma et al. (2014) |
| C57Bl/6N P.aeruginosa pneumonia model (PA) CF isolate AA43- embedded in agar beads (i.t.) ± glycol split LMWH, C3gs20 vs. N-acetyl LMWH, C23 s.c. |
Day 1: PA- agar beads (1-2 x 106) vs. sterile beads i.t. Day 1-14: C3gs20 or C23 (30 mg/kg/d) or vehicle s.c. Day 14: BAL and lung harvest Day 1: PA- agar beads (1-2 x 106) vs. sterile beads i.t. Day 10-28: C3gs20 or C23 (30 mg/kg/d) or vehicle s.c. Day 28: BAL and lung harvest |
C23 decreased BAL total cells and PMN; No significant change in PA CFU. C3gs and C23 decreased BAL total cells and PMN, decreased total PA CFU, and decreased IL-17A C3gs20 decreased IL-1β, IL-12pp40, G-CSF, and KC |
Lore et al. (2018) |
| C57BL/6J mice Allergic Asthma model OVA i.p. sensitization and challenge with Ova ± sulfated non-anticoagulant LMWH (S-NACH) i.p. |
Wk 1: Alum/Ova i.p.once per wk x 2 Wk 2-4: Ova 3% inhaled 3x per week S-NACH (10 mg/kg) or NS i.p. Week 5: BAL and lung harvest |
S-NACH decreased Ova-triggered eosinophils, macrophages, lymphocytes in BAL, decreased goblet cell metaplasia, decreased lung tissue hydroxyproline, decreased BAL and serum T2 cytokines, decreased Ova-IgE. | Ghonim et al. (2018) |
| C57BL/6 mice: LL-37- induced rhinosinusitis model LL37 i.n.± polysulfated HA (GM-0111) or HA i.n. |
Day 1: LL-37 (115 μg) GM-0111 or HA (800μg) Day 2: sinus harvest |
LL-37 increases Mast cells, MPO, lamina propria (LP) thickening and cell death GM-0111+LL-37: Decreased Mast cells, MPO, LP thickening and cell death GM-0111 more effective than HA |
Pulsipher et al. (2017) |
| BALB/c mice: Aspergillus chronic rhinosinusitis (CRS) model A.fumigatus extract ± polysulfated HA (GM-1111) or PBS i.n. 3 Groups: 1. 1. PBS 2. 2. A fumigatus+ PBS 3. 3. A. fumigatus+ GM-1111 |
Week 0: All groups sensitized with Alum + PBS or A.fumigatus i.p. Weeks 1-8: PBS or A.fumigatus extract (20,000 PNU i.n.) 3 x per wk. Weeks 5-8: PBS or GM-1111 (600 μg) i.n.5x per wk Week 9: Collect blood and sinonasal tissue |
GM-1111+ A.fumigatus (Af) extract decreased Af-induced CRS symptoms, mucosal edema and injury, goblet cells, TLR2 and TLR4, T2 cytokines, and IgE | Alt et al. (2018) |
| C57BL/6 mice Second hand smoke model of lung disease ± sulfated semisynthetic HA GAG ethers (SAGEs) |
SHS vs. Rm air nasal inhalation 10 min/day x 5 d/wk 4 weeks exposure SAGE (30 mg/kg) i.p. for 3 d/wk Collect BAL and lung RNA and protein |
SAGEs effect on SHS exposure: Blocked lung RAGE expression Blocked BAL protein, total cells, and cytokines: IL-α, IL-2, TNFα |
Tsai et al. (2019) |
| Sprague Dawley rats Rat Emphysema Model with SU51416 (VEGFR inhibitor)± polysulfated dehydropolymer of caffeic acid (CDSO3) 3 Groups: Untreated healthy SU5416 + NS SU5416 + CDSO3 |
Day 1: SU5416 (20 mg/kg) s.c. ± Day 1–Day 21: CDSO3 (60 μg/kg) or NS inhaled 3x per week |
CDSO3 prevented SU5416-induced emphysema, improved rat exercise endurance, decreased oxidative stress, and increased VEGF and HIF-1α, and decreased cleaved caspase-3 | Truong et al. (2017) |
BAL, bronchoalveolar lavage; HIF-1α, hypoxia inducible factor- 1α; i.n., intranasal; i.p., intraperitoneal; i.t., intratracheal; KC, keratinocyte chemoattractant; LMWH, low molecular weight heparin; MPO, myeloperoxidase; PMN, neutrophil; PNU, protein neoantigen units; o.a., oropharyngeal aspiration; RAGE, receptor for advanced glycation end products; s.c., subcutaneous; SHS, second hand smoke; TNFα, tumor necrosis factor α; VEGF, vascular endothelial growth factor.
The bolded text are to emphasize the stimuli for the model type and the drugs used to treat this model.