Domingo J L, Sanchez D J, Gomez M, Llobet J M, Corbella J
Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona, Reus, Spain.
Vet Hum Toxicol. 1993 Dec;35(6):495-500.
It has been shown that improvement of glucose homeostasis by oral vanadate or vanadyl treatment in streptozotocin-induced diabetic rats is accompanied by severe negative side effects (some deaths, decreased weight gain, alteration in renal function as well as tissue vanadium accumulation) which argue against the use of vanadium compounds in diabetes treatment. The present study was undertaken to assess the effectiveness in alleviating some signs of diabetes in streptozotocin-treated rats with oral therapy with sodium metavanadate (NaVO3) and sodium 4,5 dihydroxybenzene-1,3-disulfonate (Tiron), a chelating agent effective in mobilizing vanadium. In a preliminary experiment, diabetic rats were given aqueous solutions of 0.20 mg NaVO3/ml for 4 days. Vanadium-treated rats which showed blood glucose levels significantly lower (p < 0.001) than vanadate-untreated diabetic rats were selected for subsequent experiments. These animals were given 0.20 mg NaVO3/ml in drinking water and 0, 125.6, 314 or 628 mg Tiron/kg/d by gavage for 2 w. Although most of the animals did not become normoglycemic, several characteristic signs of diabetes (hyperglycemia, hyperphagia and polydipsia) were alleviated by the NaVO3 treatment. The administration of 314 mg Tiron/kg/d (approximately 1 NaVO3: 5 Tiron, mole ratio) did not diminish the ameliorative effects of NaVO3 with respect to diabetes, but significantly decreased the level of vanadium accumulation in target organs. These results show that some of the beneficial effects of NaVO3 are maintained in diabetic animals given Tiron, while the administration of the chelator results in a significant decrease in tissue vanadium accumulation. Accordingly, this would diminish the possibility of toxic side effects derived from prolonged oral vanadium administration.
研究表明，用钒酸盐或氧钒治疗链脲佐菌素诱导的糖尿病大鼠，虽能改善葡萄糖稳态，但会伴随严重的负面副作用（一些大鼠死亡、体重增加减缓、肾功能改变以及组织钒蓄积），这表明不适合将钒化合物用于糖尿病治疗。本研究旨在评估用偏钒酸钠（NaVO3）和4,5 -二羟基苯 - 1,3 -二磺酸钠（Tiron，一种有效螯合钒的螯合剂）口服治疗链脲佐菌素处理的大鼠，对缓解糖尿病某些症状的有效性。在初步实验中，给糖尿病大鼠连续4天给予浓度为0.20 mg NaVO3/ml的水溶液。选择血糖水平显著低于未用钒酸盐处理的糖尿病大鼠（p < 0.001）的经钒处理大鼠用于后续实验。这些动物饮用含0.20 mg NaVO3/ml的水，并通过灌胃给予0、125.6、314或628 mg Tiron/kg/d，持续2周。尽管大多数动物未恢复正常血糖，但NaVO3治疗减轻了糖尿病的几个特征性症状（高血糖、多食和多饮）。给予314 mg Tiron/kg/d（摩尔比约为1 NaVO3: 5 Tiron）并不降低NaVO3对糖尿病的改善作用，但显著降低了靶器官中的钒蓄积水平。这些结果表明，在给予Tiron的糖尿病动物中，NaVO3的一些有益作用得以维持，而给予螯合剂可显著降低组织钒蓄积。因此，这将减少长期口服钒所产生毒副作用的可能性。
