Effect of BRX-220 against peripheral neuropathy and insulin resistance in diabetic rat models.
Bimoclomol (BML), a symptomatic antidiabetic agent, has been developed by Biorex R & D Co. to treat diabetic neuropathy and retinopathy. BRX-220, an orally active member of the BRX family, has been developed to treat diabetic complications and insulin resistance (IR) as a follow-up compound. The effect of BRX-220 on peripheral neuropathy was examined in rats with diabetes (type 1) induced by administration of a beta-cell toxin, streptozotocin (STZ, 45 mg/kg iv). Nerve functions were evaluated by electrophysiological measurements of muscle motor and sensory nerve conduction velocities (MNCV and SNCV, respectively). MNCV and SNCV decreased in diabetic rats by 25% (p < 0.001). A 1-month preventive treatment with BRX-220 (2.5, 5, 10, and 20 mg/kg po) dose-dependently improved diabetes-related deficits in MNCV (51.3%, 71.3%, 86.1%, and 91.3%) and SNCV (48.9%, 68.5%, 86.1%, and 93.2%). Insulin sensitivity was measured using the insulin tolerance test (ITT), both in STZ diabetic and in Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). Severe IR was detected in STZ diabetic and ZDF rats. This resistance was significantly (p < 0.05) reduced by BRX-220 treatment.
Kürthy
Maria
M
Biorex Research and Development Company, Veszprém, Hungary. Maria.Kurthy@biorex.hu
Mogyorósi
Tamás
T
Nagy
Károly
K
Kukorelli
Tibor
T
Jednákovits
Andrea
A
Tálosi
László
L
Bíró
Katalin
K
D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D006146:Guanidines / Q000494:pharmacology; D006898:Hydroxylamines / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000494:pharmacology; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D013311:Streptozocin; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones
D006146:Guanidines; D006898:Hydroxylamines; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D013311:Streptozocin; D008687:Metformin; C486387:arimoclomol; C004479:pimagedine; D000077205:Pioglitazone