title: Ethyl pyruvate inhibits retinal pathogenic neovascularization by downregulating HMGB1 expression.
abstract: Retinal pathogenic angiogenesis in the eyes is a causative factor in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. This study was designed to examine the pathogenic role of the high-mobility group box-1 (HMGB1) protein and the inhibitory effect of ethyl pyruvate (EP), a well-known antioxidant substance, in retinal pathogenic angiogenesis in mice with oxygen-induced retinopathy (OIR), one of the animal models of proliferative ischemic retinopathy. The OIR mouse model was used for our in vivo studies. The mice were exposed to 75% oxygen from postnatal day 7 (P7) to P11, after which the mice were brought to room air and intraperitoneally injected with EP (50 mg/kg, or 100 mg/kg) for five days. At P17, the mice were perfused with fluorescein isothiocyanate-dextran, and flat-mounted retinas were used to measure nonperfused and neovascular tufts. In OIR mice, an intraperitoneal injection of EP reduced the nonperfused retinal area in the treatment group and significantly reduced the retinal neovascular tufts. In addition, EP inhibited the overexpression of HMGB1 in the retinas of OIR mice. These data suggest that EP could serve as an innovative pharmaceutical agent to prevent retinal neovascularization through inhibiting HMGB1 expression.
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Kyuhyung
authors.initials: K
authors.lastname: Jo
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: So Dam
authors.initials: SD
authors.lastname: Shin
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Chan-Sik
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Sohn
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Seon Gi
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000494:pharmacology; D011773:Pyruvates / Q000627:therapeutic use*; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000188:drug therapy*
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D011773:Pyruvates; C046522:ethyl pyruvate; D010100:Oxygen