RESUMO
Cemtirestat, a bifunctional drug acting as an aldose reductase inhibitor with antioxidant ability, is considered a promising candidate for the treatment of diabetic neuropathy. Our study firstly examined the effects of prolonged cemtirestat treatment on bone parameters reflecting bone quality in non-diabetic rats and rats with streptozotocin (STZ)-induced diabetes. Experimental animals were assigned to four groups: non-diabetic rats, non-diabetic rats treated with cemtirestat, diabetic rats, and diabetic rats treated with cemtirestat. Higher levels of plasma glucose, triglycerides, cholesterol, glycated hemoglobin, magnesium, reduced femoral weight and length, bone mineral density and content, parameters characterizing trabecular bone mass and microarchitecture, cortical microarchitecture and geometry, and bone mechanical properties were determined in STZ-induced diabetic versus non-diabetic rats. Treatment with cemtirestat did not affect all aforementioned parameters in non-diabetic animals, suggesting that this drug is safe. In diabetic rats, cemtirestat supplementation reduced plasma triglyceride levels, increased the Haversian canal area and slightly, but insignificantly, improved bone mineral content. Nevertheless, the insufficient effect of cemtirestat treatment on diabetic bone disease does not support its use in the therapy of this complication of type 1 diabetes mellitus.
RESUMO
BACKGROUND: Histamine H1 receptor antagonists are widely used in the treatment of allergic diseases. H1 receptors are expressed on bone cells and histamine takes part in regulation of bone metabolism. Loratadine is often prescribed to children. PURPOSE: The aim of the present study was to investigate the effects of loratadine on the skeletal system of young rats. MATERIAL AND METHODS: Loratadine (0.5, 5, and 50 mg/kg p.o. daily) was administered for 4 weeks to male Wistar rats, 6-week-old at the start of the experiment. Bone mass, mass of bone mineral, calcium, and phosphorus content in the bone mineral of the tibia, femur, and L-4 vertebra, histomorphometric parameters of the femur, mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck, and serum levels of bone turnover markers were examined. RESULTS: Loratadine at 0.5 and 5 mg/kg did not significantly affect the skeletal system of young rats. At 50 mg/kg, loratadine decreased the femoral length, increased content of calcium and phosphorus in the bone mineral of the vertebra, and tended to improve mechanical properties of the tibial metaphysis. CONCLUSION: High-dose loratadine slightly but significantly affected development of the skeletal system in rapidly growing rats.