Aldose Reductase Inhibitors Improve Myocardial Reperfusion Injury in Mice by a Dual Mechanism

Aldose reductase mediates myocardial ischemia-reperfusion injury in part by opening mitochondrial permeability transition pore.

Aldose reductase (AR), a member of the aldo-keto reductase family, has been demonstrated to play a central role in mediating myocardial ischemia-reperfusion (I/R) injury. Recently, using transgenic mice broadly overexpressing human AR (ARTg), we demonstrated that AR is an important component of myocardial I/R injury and that inhibition of this enzyme protects heart from I/R injury (20-22, 48, 4...

Central role for aldose reductase pathway in myocardial ischemic injury.

Aldose reductase (AR), a member of the aldo-keto reductase family, has been implicated in the development of vascular and neurological complications of diabetes. Recently, we demonstrated that aldose reductase is a component of myocardial ischemic injury and that inhibitors of this enzyme protect rat hearts from ischemia-reperfusion injury. To rigorously test the effect of aldose reductase on m...

Current status of aldose reductase inhibitors.

Selective irreversible inhibitors of aldose reductase.

A series of 5-substituted-1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid analogues have been examined as irreversible inhibitors of aldose reductase. The 5-alpha-bromoacetamide and 5-alpha-iodoacetamide analogues 5 and 6 gave irreversible inhibition of aldose reductase while the 5-alpha-chloroacetamide analogue 3 did not show this type of inhibition. Protection studies indicate that irreve...

Aldose reductase inhibitors of plant origin.

Diabetic complications are attributed to hyperglycaemic condition which is in turn associated with the polyol pathway and advanced glycation end products. Aldose reductase (AR) is the principal enzyme of polyol pathway which plays a vital role in the development of diabetic complications. AR inhibitory activity can be screened by both in vitro and in vivo methods. In vitro assays for AR enzyme ...