Abstract
Background/Aims: IB and IN have been shown to improve oxygen-induced retinopathy in mice. The effects of IB and IN on VEGF, IGF-I, and GH (regulators of growth and retinal development) have not been studied. We hypothesized that the effects of IB and IN are partly mediated via their action on these growth factors.
Methods: Newborn rats (n=3 litters/group; 15 pups/litter) received IP injections of saline (Sal), IB (10 mg/Kg), IB (50 mg/Kg), IN (0.2 mg/Kg), or IN (1.0 mg/Kg) on 1, 2 and 3 days postnatal age. At P14, VEGF, IGF-I and GH levels were determined in the retina, vitreous, and serum.
Results: Low doses of IB and IN had no effect on body weight or linear growth although higher serum IGF-I levels (ng/mL) were noted with 10 mg/kg IBU (386.7±30.1, p<0.05) vs Sal (282.1±19.8).). Animals treated with 50 mg/Kg IB had decreased body and organ weights (p<0.001 vs. Sal) and higher serum IGF-I levels (474.5±36.6, p<0.001 vs Sal). Animals treated with 1.0 mg/Kg IN had higher body weights (p<0.01 vs Sal) and linear growth (p<0.001 vs. Sal) and lower serum VEGF levels (101.3±12.1 pg/mL, p<0.05) vs Sal (141.7±13). In the vitreous, animals treated with 50 mg/Kg IB had higher IGF-I levels (121.9±12.1 ng/mL, p<0.05) vs Sal (80.4±4.0) and lower GH levels (2.0±0.39 ng/mL, p<0.05) vs Sal (3.53±0.37), while animals treated with 0.2 mg/kg IN had lower VEGF levels (665.6±24.2 pg/mL, p<0.01) vs Sal (906.3±31.1). In the retina, VEGF levels (pg/mg protein) were suppressed with 50 mg/Kg IB (143.6±11.4, p<0.01 vs Sal (191.2±14.7), but elevated with 1.0 mg/Kg IN (238.7±22.4, p<0.05 vs Sal).
Conclusions: High doses of IB increased total serum IGF-I levels, and decreased body and organ weights indicating decreased IGF-I bioactivity. Suppression of retinal VEGF by IB may suggest a potential therapy if administered during the vasoproliferative phase of retinopathy of prematurity.
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Modanlou, H., Hasan, J., Aranda, J. et al. 251 Effects of Ibuprofen and Indomethacin on VEGF, IGF-I, and GH in the Rat Retina, Vitreous, and Serum. Pediatr Res 58, 397 (2005). https://doi.org/10.1203/00006450-200508000-00280
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DOI: https://doi.org/10.1203/00006450-200508000-00280
