Inhibitory effects of bucillamine on increased blood-retinal barrier permeability in streptozotocin-induced diabetic rats.
OBJECTIVE
To investigate the effect of bucillamine for prevention of increasing blood-retinal barrier (BRB) permeability in streptozotocin (STZ)-induced diabetic rats.


METHODS
The groups included control and STZ-induced diabetic rats treated with or without bucillamine. Six months after intervention, the concentrations of reduced and oxidative glutathione (GSH and GSSG) in the retina were measured biochemically. In addition, vitreous fluorescein, which leaks from the vessels after intravenous injection of fluorescein sodium, was measured to evaluate BRB permeability. To evaluate the scavenging ability against the reactive oxygen species (ROS) in vitro, the second-order rate constant for the reaction of bucillamine with ROS was estimated from the kinetics based on the rate constant for the reaction of ROS.


RESULTS
The BRB permeability was significantly higher (p = 0.01) in diabetic rats not treated with bucillamine, and bucillamine inhibited the BRB permeability. The GSH concentration and the GSH/GSSG ratio in the retinas decreased in diabetic rats not treated with bucillamine; bucillamine inhibited the decrease of the GSH concentrations. The ROS scavenging activity of bucillamine was similar with that of GSH.


CONCLUSIONS
In diabetic retinas, oxidative stress might increase, which may be one of the causes of BRB breakdown. The antioxidant effects of bucillamine might take part in inhibition of increased permeability of the BRB in diabetes.
Hikichi
Taiichi
T
Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Japan. hikichi@asahikawa-med.ac.jp
Mori
Fumihiko
F
Nakamura
Masao
M
Shishido
Naomi
N
Sasaki
Mai
M
Horikawa
Yoshitaka
Y
Yoshida
Akitoshi
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001813:Blood-Retinal Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D012171:Retinal Vessels / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005978:Glutathione; D003545:Cysteine; C026535:bucillamine; D019803:Glutathione Disulfide