Abstract:
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.
摘要:
Cemtirestat,一种具有抗氧化能力的作为醛糖还原酶抑制剂的双功能药物,被认为是治疗糖尿病神经病变的有希望的候选者。我们的研究首先检查了长时间的骨水泥司他治疗对非糖尿病大鼠和链脲佐菌素(STZ)诱导的糖尿病大鼠中反映骨质量的骨参数的影响。实验动物分为四组:非糖尿病大鼠,用骨替司他治疗的非糖尿病大鼠,糖尿病大鼠,和糖尿病大鼠用cemtirestat治疗。血浆葡萄糖水平较高,甘油三酯,胆固醇,糖化血红蛋白,镁,减少股骨重量和长度,骨矿物质密度和含量,表征骨小梁质量和微结构的参数,皮质微结构和几何学,并测定了STZ诱导的糖尿病和非糖尿病大鼠的骨力学特性。在非糖尿病动物中,用骨水泥司他治疗并不影响上述所有参数,表明这种药物是安全的.在糖尿病大鼠中,补充西替司他降低了血浆甘油三酯水平,增加了哈弗斯运河面积,但无关紧要,改善骨矿物质含量。然而,骨水泥司他对糖尿病性骨病的治疗效果不足,这并不支持将其用于治疗1型糖尿病的这种并发症.