We investigated the effects of
actinonin, an inhibitor of a matrix-degrading
enzyme meprin, on ischemic
acute kidney injury in male and female rats, and these were compared with the effects of
verapamil, a Ca(2+) channel blocker. Ischemic
acute kidney injury was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral
nephrectomy. At 24 h after reperfusion, renal function and histology of both males and females showed significant deterioration. The degrees of renal dysfunction and histological damage were much more severe in males than in females. Pre-ischemic treatment with
actinonin (10 or 30 mg/kg, i.v.) dose-dependently attenuated the
ischemia/reperfusion-induced renal injury in male rats, but failed to improve the renal injury in female rats. On the other hand,
verapamil (1 mg/kg, i.v.) could efficiently prevent the ischemic
acute kidney injury in female rats, as well as male rats. These results indicate that the renoprotective effect of
actinonin is male-specific, thereby suggesting that
meprin is involved in exacerbation of
ischemia/reperfusion-induced renal injury in male rats. The possibility that
meprin is a key factor involved in the sex difference in the pathogenesis of ischemic
acute kidney injury, warrants further attention.