The antagonism of cholecystokinin octapeptide-8 to the peroxynitrite oxidation on a diabetic cataractal rat model.
BACKGROUND
Cataracts is considered be formed because of an abnormal glucose metabolic pathway or oxidative stress. We explored the damaging role of ONOO- and antagonism of cholecystokinin octapeptide-8 (CCK-8) in diabetic cataractal rat lenses.


METHODS
A diabetic cataractal animal model was established by peritoneal injection of streptozotocine (STZ). Thirty-six normal SD rats were taken as control group; seventy-two were given STZ (45 mg/kg) and then divided into STZ group and CCK-8 group (peritoneal injection CCK-8). STZ induced diabetic rats were treated with CCK-8 for 60 days. Lenses were examined with slit lamp at 20, 40 and 60 days. Immunofluorescent staining and Western blot analysis were used for determining nitrotyrosine (NT, a marker for ONOO-). PT-PCR and gene array analysis were used for determining the expression of inducible nitric oxide synthetase mRNA (iNOS mRNA) in lens epithelium (LEC).


RESULTS
STZ group rats developed lens opacity by 20 days that reached a high level by 60 days after STZ injection. CCK-8 group rats delayed the cataract formation. CCK-8 group rats delayed the cataract formation. There was no distinct expression of NT and iNOS mRNA in control group. In STZ group, there were distinct expression of NT and upregulation of iNOS mRNA; however, CCK-8 group showed weak expression of NT and downregulation of iNOS mRNA.


CONCLUSIONS
NT, which may be a new form of oxidative stress, was expressed in diabetic rat LEC although CCK-8 could reverse NT damage in LEC. The results suggested that CCK-8 might be a useful therapeutic agent against diabetic cataract. The antagonizing mechanism of CCK-8 may be related to direct antagonism of ONOO- as well as its inhibition of the expression of iNOS mRNA for production of NO and therefore decrease in the formation of ONOO-.
Hao
Li-na
LN
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050011, China.
Ling
Yi-qun
YQ
Mao
Qi-yan
QY
Ling
Yi-ling
YL
He
Shou-zhi
SZ
D000818:Animals; D015153:Blotting, Western; D002386:Cataract / Q000209:etiology* / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D005455:Fluorescent Antibody Technique; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012844:Sincalide / Q000494:pharmacology*; D013311:Streptozocin; D014443:Tyrosine / Q000031:analogs & derivatives / Q000235:genetics
D012333:RNA, Messenger; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D013311:Streptozocin; D052247:Nitric Oxide Synthase Type II; D012844:Sincalide