Departamento de Fisiologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Pará, 1720, Uberlândia Zip Code 38405-320, Minas Gerais, Brazil.
Departamento de Fisiologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Pará, 1720, Uberlândia Zip Code 38405-320, Minas Gerais, Brazil.
J Pharmacol Toxicol Methods. 2021 Nov-Dec;112:107090. doi: 10.1016/j.vascn.2021.107090. Epub 2021 Jun 25.
Previous data indicate that the diabetogenic substance streptozotocin might act in nociceptive neurons changing the sensory signal, regardless of hyperglycemia. In the present article the effects of streptozotocin were compared with another diabetogenic drug, alloxan, for diabetes induction in rats. A possible direct effect of these drugs was tested by means of in vivo experiments and in vitro assays using cultured primary nociceptive neurons. Streptozotocin (17.5 and 35 mg/kg), alloxan (15 and 30 mg/kg) or vehicle were injected in adult male rats and the animal groups were separated according to glycemic levels. Body mass, glycemia and paw mechanical sensitivity were evaluated for 5 weeks. Streptozotocin caused an increase in mechanical sensitivity in both hyperglycemic and normoglycemic rats, while alloxan induced mechanical sensitization only in hyperglycemic animals. Injection of both substances induced local inflammation at rat paws; however, only streptozotocin caused significant mechanical sensitization when injected near to sensory neurons at the dorsal root ganglia. Also, streptozotocin treatment induced a reduction in intracellular calcium levels and inhibited capsaicin induced calcium transients and membrane depolarization. Alloxan did not affect calcium levels or membrane potential in primary nociceptive neurons. These findings suggest that alloxan might be a better option for animal studies regarding painful diabetic neuropathy as streptozotocin directly affects nociceptive neurons, probably by modulating TRPV1 channel activation.
先前的数据表明，致糖尿病物质链脲佐菌素可能作用于伤害感受神经元，改变感觉信号，而与高血糖无关。在本文中，我们比较了链脲佐菌素和另一种致糖尿病药物——链脲佐菌素，以观察它们在诱导大鼠糖尿病方面的作用。通过体内实验和体外培养的初级伤害感受神经元检测，研究了这些药物的可能直接作用。链脲佐菌素（17.5 和 35mg/kg）、链脲佐菌素（15 和 30mg/kg）或载体分别注射到成年雄性大鼠体内，根据血糖水平将动物分组。在 5 周的时间里，评估了体重、血糖和爪机械敏感性。链脲佐菌素导致高血糖和正常血糖大鼠的机械敏感性增加，而链脲佐菌素仅导致高血糖动物的机械敏感性增加。两种物质的注射都会在大鼠爪子引起局部炎症；然而，只有当链脲佐菌素注射到背根神经节的感觉神经元附近时，才会引起明显的机械敏感性。此外，链脲佐菌素处理还会降低细胞内钙水平，并抑制辣椒素诱导的钙瞬变和膜去极化。链脲佐菌素对初级伤害感受神经元中的钙水平或膜电位没有影响。这些发现表明，链脲佐菌素可能是研究痛性糖尿病性神经病变的更好选择，因为链脲佐菌素直接作用于伤害感受神经元，可能通过调节 TRPV1 通道的激活来实现。
