Skeletal muscle post-conditioning by diazoxide, anti-oxidative and anti-apoptotic mechanisms.
Mol Biol Rep
; 39(12): 11093-103, 2012 Dec.
Article
in En
| MEDLINE
| ID: mdl-23053996
ABSTRACT
Pretreatment with diazoxide, K(ATP) channel opener, increases tissue tolerance against ischemia reperfusion (IR) injury. In clinical settings pretreatment is rarely an option therefore we evaluated the effect of post-ischemic treatment with diazoxide on skeletal muscle IR injury. Rats were treated with either saline, diazoxide (K(ATP) opener; 40 mg/kg) or 5-hydroxydecanoate (5-HD; mitochondrial K(ATP) inhibitor; 40 mg/kg) after skeletal muscle ischemia (3 h) and reperfusion (6, 24 or 48 h). Tissue contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activities, Bax and Bcl-2 protein expression and muscle histology were determined. Apoptosis was examined (24 and 48 h) after ischemia. IR induced severe histological damage, increased MDA content and Bax expression (24 and 48 h; p < 0.01) and decreased CAT and SOD activities (6 and 24 h, p < 0.01 and 48 h, p < 0.05), with no significant effect on Bcl-2 expression. Diazoxide reversed IR effects on MDA (6 and 24 h; p < 0.05), SOD (6 and 24 h; p < 0.01) and CAT (6 and 48 h, p < 0.05 and 24 h p < 0.01) and tissue damage. Diazoxide also decreased Bax (24 and 48 h; p < 0.05) and increased Bcl-2 protein expression (24 and 48 h; p < 0.01). Post-ischemic treatment with 5-HD had no significant effect on IR injury. Number of apoptotic nuclei in IR and 5-HD treated groups significantly increased (p < 0.001) while diazoxide decreased apoptosis (p < 0.01). The results suggested that post-ischemic treatment with diazoxide decrease oxidative stress in acute phase which modulates expression of apoptotic proteins in the late phase of reperfusion injury. Involvement of KATP channels in this effect require further evaluations.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apoptosis
/
Muscle, Skeletal
/
Diazoxide
/
Ischemic Postconditioning
Limits:
Animals
Language:
En
Journal:
Mol Biol Rep
Year:
2012
Type:
Article
Affiliation country:
Iran