Effect of artesunate on endotoxin-induced uveitis in rats.
OBJECTIVE
The purpose of this study was to explore the effect of artesunate on endotoxin-induced uveitis (EIU) in rats.


METHODS
EIU was induced in male Long-Evans rats by footpad injection of lipopolysaccharide (LPS 200 μg in 0.1 mL PBS; LPS-only group [LG]). PBS (0.1 mL), prednisolone (10 mg/kg in 0.1 mL PBS; prednisolone group [PG]), and artesunate of three concentrations (1, 10, 100 mg/kg; artesunate groups A, B, C [AGA, AGB, AGC]; all in 0.1 mL of PBS) were injected intravenously, respectively, 1 hour after LPS injection. Twenty-four hours after LPS injection, infiltrating cells and protein concentration in the aqueous humor, as well as tumor necrosis factor (TNF)-α, nitric oxide (NO), prostaglandin E2 (PGE2), and monocyte chemoattractant protein (MCP)-1, were measured.


RESULTS
Rats in AGA did not have significant difference in infiltrating cell number (61.6 × 10(5) cells/mL; range, 20.0-147.8 cells/mL; P = 0.287), protein concentration (48.0 mg/mL; range, 18.0-101.8 mg/mL; P = 0.349), NO concentration (86.9 μM/L; range, 30.5-192.5 μM/L; P = 0.363), but had significant difference in TNF-α (1144.3 pg/mL; range, 460.0-1840.0 pg/mL; P = 0.038), PGE2 (12.8 ng/mL; range, 4.8-27.2 ng/mL; P = 0.005), and MCP-1 (6136 pg/mL; range, 20.0-147.8 pg/mL; P = 0.009) with those of LG. Artesunate at 10 mg/kg and 100 mg/kg significantly suppressed the infiltrating cells, protein concentration, TNF-α, NO, PGE2, and MCP-1 in the aqueous humor induced by LPS (P = 0.011-0.000).


CONCLUSIONS
Dose-dependent decreases of infiltrating cells, protein concentration, TNF-α, PGE2, NO, and MCP-1 in the aqueous humor by artesunate treatment after LPS injection indicate that artesunate can suppress the inflammation of EIU by inhibiting the production of inflammatory mediators.
Wang
Xiao-Qin
XQ
Department of Pharmacology, Third Military Medical University, Chongqing 400038, China. wxqwsh@163.com
Liu
Hai-Lin
HL
Wang
Gui-Bo
GB
Wu
Peng-Fei
PF
Yan
Tian
T
Xie
Jia
J
Tang
Yong
Y
Sun
Lu-Kun
LK
Li
Chen
C
D000818:Animals; D001082:Aqueous Humor / Q000166:cytology / Q000378:metabolism; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D018932:Chemokine CCL2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D037621:Artemisinins; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005136:Eye Proteins; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000077332:Artesunate; D015232:Dinoprostone