title: Curcumin suppresses N-methyl-N-nitrosourea-induced photoreceptor apoptosis in Sprague-Dawley rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology II, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1010, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Emoto
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Norihisa
authors.initials: N
authors.lastname: Uehara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Takashi
authors.initials: T
authors.lastname: Yuri
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shikata
authors.forename: Airo
authors.initials: A
authors.lastname: Tsubura
mesh_terms: D000477:Alkylating Agents / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D008770:Methylnitrosourea / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000473:pathology
chemical_list: D000477:Alkylating Agents; D000975:Antioxidants; D008770:Methylnitrosourea; D003474:Curcumin
keywords: 8-OHdG; 8-hydroxy-2-deoxyguanosine; Apoptosis; MNU; N-methyl-N-nitrosourea; TUNEL; TdT-mediated dUTP-digoxigenin nick-end labeling; curcumin; oxidative stress; photoreceptor; rat; retina; retinal degeneration; retinitis pigmentosa