sulindac and Diabetic-Neuropathies

A study comparing ibuprofen (600 mg four times a day) vs sulindac (200 mg twice a day), and a placebo in the treatment of painful diabetic peripheral neuropathy was conducted in 18 male outpatients. Discomfort was characterized and rated with a subjective neuropathy score. The response to both ibuprofen and sulindac was better than it was to placebo in the entire group. There were no changes in glucose control or renal function. Further studies are necessary to evaluate the significance of aldose reductase-inhibitor properties of nonsteroidal anti-inflammatory drugs and to select the "best" one of these drugs for the treatment of diabetic neuropathy.

Topics: Aldehyde Reductase; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Diabetic Neuropathies; Humans; Ibuprofen; Male; Middle Aged; Sulindac

The purpose of this study was to define pathological abnormalities in the peripheral nerve of a large animal model of long-duration type 1 diabetes and also to determine the effects of treatment with sulindac. Detailed morphometric studies were performed to define nerve fiber and endoneurial capillary pathology in 6 control dogs, 6 type 1 diabetic dogs treated with insulin, and 6 type 1 diabetic dogs treated with insulin and sulindac for 4 years. Myelinated fiber and regenerative cluster density showed a non-significant trend toward a reduction in diabetic compared to control animals, which was prevented by treatment with sulindac. Unmyelinated fiber density did not differ among groups. However, diabetic animals showed a non-significant trend toward an increase in axon diameter (p < 0.07), with a shift of the size frequency distribution towards larger axons, which was not prevented by treatment with sulindac. Endoneurial capillary density and luminal area showed a non-significant trend toward an increase in diabetic animals, which was prevented with sulindac treatment. Endoneurial capillary basement membrane area was significantly increased (p < 0.05) in diabetic animals, but was not prevented with sulindac treatment. We conclude that the type 1 diabetic dog demonstrates minor structural abnormalities in the nerve fibers and endoneurial capillaries of the sciatic nerve, and treatment with sulindac ameliorates some but not all of these abnormalities.

Topics: Animals; Capillaries; Cyclooxygenase Inhibitors; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Dogs; Microscopy, Electron; Nerve Fibers; Nerve Fibers, Myelinated; Sciatic Nerve; Sulindac

We studied the influence of sulindac, a nonsteroidal anti-inflammatory agent on experimental streptozotocin-induced diabetic neuropathy. Untreated diabetic rats were compared with nondiabetic rats, diabetic rats treated with low dose insulin and diabetic rats given sulindac (6.0 mg/kg by gavage 5 of 7 days weekly). Neuropathy was assessed by following serial in vivo motor and sensory caudal conduction, resistance to ischemic conduction failure, and in vitro conduction in sural myelinated and unmyelinated sensory fibers. The impact of low dose insulin and sulindac treatment on the microenvironment of the L4 dorsal root ganglion and sciatic endoneurium was assessed by measuring local perfusion and oxygen tension after 16 weeks of diabetes. Sulindac normalized conduction velocity in caudal sensory fibers, sural myelinated fibers and sural unmyelinated fibers, and reduced the number of diabetic cataracts. Sulindac also normalized a deficit in dorsal root ganglion blood flow and a reduction in sciatic endoneurial oxygen tension in diabetic rats. Low dose insulin improved neuropathy as well but the pattern of benefits was less robust than that of sulindac. Sulindac may be a candidate for a clinical trial in human diabetic polyneuropathy.

Topics: Animals; Capillary Resistance; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Electrophysiology; Insulin; Male; Nerve Fibers; Neural Conduction; Neurons, Afferent; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Sulindac

Sorbitol, resulting from glucose metabolism through aldose reductase, may play a role in diabetic complications such as cataracts, neuropathy, and vasculopathy. Sulindac (Clinoril) and sorbinil, two inhibitors of aldose reductase, decreased sorbitol formation in cataract or nerve tissue incubated in high glucose TC-199 media. Sulindac, a widely used anti-rheumatic drug, may have clinical applications in preventing diabetic complications.

Topics: Aldehyde Reductase; Animals; Diabetic Neuropathies; Diabetic Retinopathy; Imidazoles; Imidazolidines; Indenes; Lens, Crystalline; Rabbits; Rats; Sciatic Nerve; Sorbitol; Sugar Alcohol Dehydrogenases; Sulindac