Curcumin suppresses N-methyl-N-nitrosourea-induced photoreceptor apoptosis in Sprague-Dawley rats

Retinitis pigmentosa is a group of inherited neurodegenerative human diseases characterized by the loss of photoreceptor cells by apoptosis and lead to eventual blindness. A single intraperitoneal (i.p.) injection of N-methyl-N-nitrosourea (MNU), an alkylating agent, causes photoreceptor cell apoptosis within seven days in rats. Curcumin is a polyphenolic natural product with pluripotent properties including antioxidant activity. The purpose of the present study was to evaluate the efficacy of curcumin against photoreceptor apoptosis in a MNU-induced retinal degeneration rat model.

Seven-week-old female Sprague-Dawley rats received a single i.p. injection of 40 mg/kg MNU. Three days prior to MNU injection, daily i.p. injections of 100 or 200 mg/kg curcumin were started, and the injections were continued once daily until sacrifice. Rats were sacrificed at 6, 12, 24 and 72 h, and 7 days after MNU, and their eyes were examined morphologically and morphometrically to evaluate the photoreceptor cell ratio and retinal damage ratio in hematoxylin and eosin-stained sections. Retinal 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were quantified by enzyme-linked immunosorbent assay (ELISA), and the apoptotic cell ratio in photoreceptor cells was determined in situ by TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL).

Curcumin (200 mg/kg) significantly (p<0.01) suppressed the loss of photoreceptor cells, as determined by the photoreceptor cell ratio at the central retina seven days after MNU, and this effect was dose-dependent. At 12 h after MNU injection, when the oxidative DNA damage caused by MNU peaked, curcumin significantly reduced the level of 8-OHdG (0.78 vs. 0.50 ng/ml) (p<0.05) and the percentage of TUNEL-positive photoreceptor cells (17.5% vs. 10.8%) (p<0.05) as compared with MNU-exposed, curcumin-untreated retina, respectively.

Curcumin inhibited MNU-induced photoreceptor cell apoptosis by suppressing DNA oxidative stress. These findings indicate that curcumin may help to suppress the onset and progression of human retinitis pigmentosa.