Comparação entre estreptozotocina e aloxana como indutores de diabetes experimental para estudos dos mecanismos envolvidos na neuropatia diabética

Abstract

Diabetes mellitus is a disease with high worldwide prevalence. Animal models of experimental diabetes play a key role in elucidating the pathogenesis of diabetes in humans and its complications, including diabetic neuropathy. The most used drugs for the induction of experimental diabetes are streptozotocin and alloxan, with a higher prevalence of the first in studies in rodents. However, there is evidence that streptozotocin may alter the sensitivity of animals treated with this drug regardless of its glycemic condition. The aim of this study was to compare the effects of streptozotocin and alloxan as inducers of experimental diabetes for studies of the mechanisms involved in diabetic neuropathy in rats. Wistar rats were used to evaluate the systemic effects of the two drugs by evaluating the mechanical and thermal sensitivities of the animals for 5 weeks in animals treated with two doses of aloxane (30 or 15 mg/kg) and streptozotocin (35 or 17.5 mg/kg). Both drugs induced similar hyperglycemia in part of the animals, while the other part remained normoglycemic. No variations in thermal sensitivity were observed at any of the times and treatments tested. Treatment with streptozotocin induced evident alterations at the mechanical sensitivity threshold, including in those animals that remained normoglycemic. Aloxane treatment induced changes in mechanical sensitivity only in the fifth week of treatment. Intraplant administration of the two drugs caused hyperalgesia and inflammation, evidenced by paw edema. Direct administration at the dorsal root ganglion (L5) promoted hyperalgesia in animals treated with streptozotocin, but not with alloxan. In vitro experiments using dorsal root ganglia primary cultures suggested a direct effect only for streptozotocin on intracellular levels of calcium in nociceptive neurons. The results suggest that both drugs have similar potential in inducing diabetes, but streptozotocin appears to have a direct effect on nociceptive neurons and this effect may hinder studies using this drug as a diabetes inducer as model for diabetic neuropathy studies. We conclude that alloxan seems to be a better alternative in the study of this complication.