title: Crocetin, a carotenoid derivative, inhibits retinal ischemic damage in mice.
abstract: Crocetin, an aglycone of crocin, is found both in the saffron crocus (Crocus starus L.) and in gardenia fruit (Gardenia jasminoides Ellis). We evaluated the protective effects of crocetin against the retinal ischemia induced by 5h unilateral ligation of both the pterygopalatine artery (PPA) and the external carotid artery (ECA) in anesthetized mice. The effects of crocetin (20mg/kg, p.o.) on ischemia/reperfusion-induced retinal damage were examined by histological, electrophysiological, and anti-apoptotic analyses. Data for anti-apoptotic analysis was obtained by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Using immunohistochemistry and immunoblotting, the protective mechanism mediating the effects of crocetin was evaluated by examining crocetin's effects on the expression of 8-hydroxy-2-deoxyguanosine (8-OHdG; used as a marker of oxidative stress) and on phosphorylations of mitogen-activated protein kinases [MAPK; viz. extracellular signal-regulated protein kinases (ERK), c-Jun N-terminal kinases (JNK) and p38], and the redox-sensitive transcription factors nuclear factor-kappa B (NF-κB) and c-Jun. The histological analysis revealed that ischemia/reperfusion (I/R) decreased the cell number in the ganglion cell layer (GCL) and the thickness of inner nuclear layer (INL), and that crocetin inhibited GCL and INL. ERG measurements revealed that crocetin prevented the I/R-induced reductions in a- and b-wave amplitudes seen at 5 days after I/R. In addition, crocetin decreased the numbers of TUNEL-positive cells and 8-OHdG-positive cells, and the phosphorylation levels of p38, JNK, NF-κB, and c-Jun present in the retina after I/R. These findings indicate that crocetin prevented ischemia-induced retinal damage through its inhibition of oxidative stress.
authors: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Fumiya
authors: F
authors: Ishizuka
authors: Masamitsu
authors: M
authors: Shimazawa
authors: Naofumi
authors: N
authors: Umigai
authors: Hiromi
authors: H
authors: Ogishima
authors: Shinsuke
authors: S
authors: Nakamura
authors: Kazuhiro
authors: K
authors: Tsuruma
authors: Hideaki
authors: H
authors: Hara
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002338:Carotenoids / Q000494:pharmacology / Q000627:therapeutic use*; D004247:DNA / Q000378:metabolism; D004596:Electroretinography; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D016328:NF-kappa B; D020011:Protective Agents; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases