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Late anti‐apoptotic effect of K ATP channel opening in skeletal muscle
Author(s) -
Farahini Hossein,
Habibey Rouhollah,
Ajami Marjan,
Davoodi Sayed Hossein,
Azad Nahid,
Soleimani Mansoureh,
TavakkoliHosseini Morteza,
PazokiToroudi Hamidreza
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12015
Subject(s) - glibenclamide , malondialdehyde , diazoxide , chemistry , apoptosis , endocrinology , skeletal muscle , medicine , superoxide dismutase , channel blocker , catalase , oxidative stress , biology , biochemistry , diabetes mellitus , insulin , calcium
Summary Necrosis and apoptosis caused by ischaemia–reperfusion ( IR ) result in myocyte death and atrophy. ATP ‐sensitive K + ( K ATP ) channels activation increases tissue tolerance of IR ‐injury. Thus, in the present study, we evaluated the effects of K ATP channel activation on skeletal muscle apoptosis after IR . Male Wistar rats were treated with 40 mg/kg, i.p., diazoxide (a K ATP channel opener) or 5 mg/kg, i.p., glibenclamide (a K ATP channel inhibitor) 30 min before the induction of 3 h ischaemia, followed by 6, 24 or 48 h reperfusion. At the end of the reperfusion period, the gastrocnemius muscle was removed for the analysis of tissue malondialdehyde content, superoxide dismutase ( SOD ) and catalase ( CAT ) activity, Bax and Bcl‐2 protein expression, histological damage and the number of apoptotic nuclei. Ischaemia–reperfusion increased malondialdehyde content ( P < 0.01) and Bax expression ( P < 0.01) and induced severe histological damage, in addition to decreasing CAT and SOD activity ( P < 0.01 and P < 0.05, respectively) and Bcl‐2 expression ( P < 0.01). Diazoxide reversed the effects of IR on tissue damage, MDA content, SOD and CAT activity (after 6 and 24 h reperfusion; P < 0.05) and Bax and Bcl‐2 expression (after 24 and 48 h reperfusion; P < 0.01). In contrast, glibenclamide pretreatment had no effect. The number of apoptotic nuclei in the IR and glibenclamide‐pretreated groups increased significantly ( P < 0.001 vs Sham). In contrast, diazoxide pretreatment decreased the number of apoptotic nuclei compared with the IR group ( P < 0.01). The results of the present study suggest that the K ATP channel activator diazoxide attenuates lipid peroxidation during the first hour of reperfusion and modulates apoptotic pathways at later time points.