Abstract
Purpose :
To compare the effect of NACA and NAC on oxidative damage-induced retinal degeneration
Methods :
C57BL/6 mice were untreated or treated with 7 mg/ml of NAC or NACA in drinking water and given daily intraperitoneal (IP) injections of 2.57 mg/kg of paraquat (PQ) daily for 7 days, or a single intravitreous injection of 514 µg of PQ. ERGs were performed 14 days after starting IP PQ or 7 days after single intravitreous injection of PQ. Then reduced to oxidized glutathione ratio (GSH/GSSG), protein carbonyl content, and malondialdehyde (MDA) was measured.
Results :
After 14 days of IP PQ, mean scotopic b-wave amplitude (µV) (1.5 cdxs/m2) in PQ control, NAC-treated, and NACA-treated mice (n=6) was, 216±27.7, 397±77.6, and 498±54.6, and 553±40.4 in normal mice (p<0.05 by ANOVA for difference between NACA and NAC) and mean photopic b-wave amplitude (1.4 cdxs/m2) was 91±19.6, 191±50.4, and 255±50.1, and 289±40.6 in normal mice (p<0.05 by ANOVA for difference between NACA and NAC). Retinal levels of MDA (µg) in PQ control, NAC, and NACA groups were 9.03±0.32, 7.75±0.16, and 6.45±0.33, and 6.3±0.56 in retinas of mice not treated with PQ). Carbonyl content (nmol/mg protein) was 2.58±0.16, 1.97±0.19, 1.47±0.14, and 1.19±0.11 in normal retina. GSH/GSSG ratio was 1.37±0.15, 1.86±0.16, and 2.98±0.18, and 3.13±0.14 in normal retina (p<0.05 by ANOVA with Bonferroni for NACA vs NAC for each of these 3 variables). Seven days after intravitreous injection of PQ, mean scotopic b-wave amplitude (µV) in PQ control, NAC-treated, and NACA-treated mice (n=6) was 156±20.4, 267±31.4, and 503±33.6, and 583±26.2 in normal mice (p<0.05 by ANOVA for difference between NACA and NAC) and mean photopic b-wave amplitude (1.4 cdxs/m2) was 97±18.4, 219±9.8, and 273±14.2, and 295±14.6 (p<0.05 NACA vs NAC). Retinal levels of MDA (µg) in PQ control, NAC, and NACA groups were 1339±0.39, 10.82±0.21and 8.16±0.21, and 6.9±0.14 in retinas of mice not treated with PQ. Carbonyl content (nmol/mg protein) was 3.39±0.29, 2.27±0.16, 1.69±0.18, and 1.28±0.18 in normal retina. GSH/GSSG ratio was 2.54±0.12; 3.52±0.16, and 4.15±0.1 compared with 4.41±0.15 in normal retina (p<0.05 for NACA vs NAC by ANOVA with Bonferroni for each of the 3 variables).
Conclusions :
Oral NACA is superior to oral NAC for prevention of PQ-induced oxidative damage and loss of function in the retina.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.