Vanadium(IV/V) compounds have been studied as possible metallopharmaceutical drugs against diabetes mellitus. However, mechanisms of action and toxicological threshold have been tackled poorly so far. In this paper, our purposes were to evaluate the metabolic activity on dyslipidemia and dysglycemia, insulin signaling in liver and adipose tissue, and toxicology of the title compound. To do so, the previously reported bisammonium tetrakis 4-(N,N-dimethylamino)pyridinium decavanadate, the formula of which is [DMAPH]₄(NH₄)₂[V₁₀O₂₈]·8H₂O (where DMAPH is 4-dimethylaminopyridinium ion), was synthesized, and its dose-response curve on hyperglycemic rats was evaluated. A Long–Evans rat model showing dyslipidemia and dysglycemia with parameters that reproduce metabolic syndrome and severe insulin resistance was generated. Two different dosages, 5 µmol and 10 µmol twice a week of the title compound (equivalent to 2.43 mg·V/kg/day and 4.86 mg·V/kg/day, resp.), were administered intraperitoneal (i.p.) for two months. Then, an improvement on each of the following parameters was observed at a 5 µmol dose: weight reduction, abdominal perimeter, fatty index, body mass index, oral glucose tolerance test, lipid profile, and adipokine and insulin resistance indexes. Nevertheless, when the toxicological profile was evaluated at a 10 µmol dose, it did not show complete improvement, tested by the liver and adipose histology, as well as by insulin receptor phosphorylation and GLUT-4 expression. In conclusion, the title compound administration produces regulation on lipids and carbohydrates, regardless of dose, but the pharmacological and toxicological threshold for cell regulation are suggested to be up to 5 µmol (2.43 mg·V/kg/day) dose twice per week.

中文翻译：

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在代谢综合征和胰岛素抵抗的大鼠模型中四酸四铵4-（N，N-二甲基氨基）吡啶鎓十钒酸盐的药理和毒理学阈值。

钒（IV / V）化合物已被研究作为可能的抗糖尿病金属药物。但是，到目前为止，作用机理和毒理学阈值尚未得到很好的解决。在本文中，我们的目的是评估对血脂异常和血糖异常的代谢活性，肝脏和脂肪组织中的胰岛素信号传导以及标题化合物的毒理学。为此，以前报道的四（4-（N，N-二甲基氨基）吡啶鎓双铵十钒酸盐）的分子式为[DMAPH] ₄（NH ₄）₂ [V ₁₀ O ₂₈ ]·8H ₂合成了O（其中DMAPH是4-二甲氨基吡啶鎓离子），并评估了其在高血糖大鼠上的剂量反应曲线。生成了具有显示代谢综合征和严重胰岛素抵抗的参数的血脂异常和血糖异常的Long-Evans大鼠模型。两个不同的剂量，5  μ mol和10  μ摩尔的标题化合物，每周两次（相当于2.43毫克·V / kg /天和4.86毫克·V / kg /天，RESP。），进行腹膜内（ip）施用对两个月 然后，观察到以下每个参数在5 µ时都有改善。 摩尔剂量：体重减轻，腹围，脂肪指数，体重指数，口服葡萄糖耐量试验，脂质分布以及脂肪因子和胰岛素抵抗指数。然而，当所述的毒理学特性在评价10  μ摩尔的剂量，它没有显示出完整的改善，由肝和脂肪组织学测试，以及由胰岛素受体磷酸化和GLUT-4的表达。总之，获得标题化合物施用产生调节上脂类和碳水化合物，无论剂量，但对细胞调节的药理学和毒理学阈值建议是高达5  μ摩尔（2.43毫克·V / kg /天），每周剂量两次。