The flavonoid baicalin counteracts ischemic and oxidative insults to retinal cells and lipid peroxidation to brain membranes.
The purpose of the present study was to determine whether the flavonoid, baicalin is effective at blunting the negative influence of ischemia/reperfusion to the rat retina in situ and of various insults to a transformed retinal ganglion cells (RGC-5 cells) in culture. Baicalin was administered intraperitoneally just before and after an ischemic insult to retina of one eye of a rat. Ischemia was delivered by raising the intraocular pressure above the systolic blood pressure for 50min. Seven days after ischemia, retinas were analysed for the localisation of various antigens. Retinal extracts were also analysed for various mRNAs. Moreover, the content of specific proteins was deduced in retinal and optic nerve extracts. Also, RGC-5 cells in culture were given one of three different insults, light (1000lx for 2 days), hydrogen peroxide (200microM H(2)O(2) for 24h) or serum deprivation (48h) where cell survival and reactive oxygen species (ROS) formation was assayed. Moreover, a lipid peroxidation assay was used to compare the antioxidant capacity of baicalin with the flavonoid, epigallocatechin gallate (EGCG). Ischemia/reperfusion to the retina affected the localisation of Thy-1 and choline acetyltransferase (ChAT) and the content of various proteins (optic nerve and retina) and mRNAs (retina). Importantly, baicalin statistically blunted most of the effects induced by ischemia/reperfusion. Only the increase in caspase-8 and caspase-3 mRNAs caused by ischemia/reperfusion were unaffected by baicalin treatment. Baicalin also attenuated significantly the negative insult of light, hydrogen peroxide and serum withdrawal to RGC-5 cells. In the lipid peroxidation studies, baicalin was also found to be equally effective as EGCG to act as an antioxidant. Significantly, the negative insult of serum withdrawal on RGC-5 cell survival was blunted by baicalin but not by EGCG revealing the different properties of the two flavonoids.
Jung
S H
SH
Nuffield Laboratory of Ophthalmology, Oxford University, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Kang
K D
KD
Ji
D
D
Fawcett
R J
RJ
Safa
R
R
Kamalden
T A
TA
Osborne
N N
NN
D000818:Animals; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000633:toxicity; D005419:Flavonoids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010775:Photic Stimulation / Q000009:adverse effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism
D016895:Culture Media, Serum-Free; D005419:Flavonoids; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D018800:Thy-1 Antigens; C038044:baicalin; D006861:Hydrogen Peroxide; D002795:Choline O-Acetyltransferase; D020169:Caspases