Título

VITAMIN D DEFICIENCY ACCELERATES THE DEVELOPMENT OF DIABETIC NEPHROPATHY IN RATS WITH TYPE 1 DIABETES

Introdução

Diabetic nephropathy (DN) is characterized by renal disturbances that can be exacerbated by the vitamin D (VitD) deficiency. The aim of this study is to evaluate the influence on the VitD deficiency on the DN development in a type 1 diabetes mellitus (T1DM) model.

Material e Método

Twenty rats received a previous diet deficient or not in VitD3 for 6 weeks. After this period, T1DM was induced by a single injection of streptozotocin (STZ; 45 mg/kg i.p.). Rats were divided into four experimental groups: control with a standard diet (SD) (Ctrl SD); control with a vitamin D deficient (VitD-) diet (Ctrl VitD-); diabetic with a SD (DM SD); diabetic with VitD- diet (DM VitD-). The animals of the different groups were followed for 24 weeks after diabetes induction. After that the rats were euthanized and serum, plasma, urine and renal tissue were collected for renal function, histological, morphometrical and immunohistochemical studies. Ethics Committee: protocol number 002/2019.

Resultados

Our data showed that rats treated with the VitD3-free diet were deficient in VitD before and after the induction of T1DM induction (P < 0.05). To simulate a decompensated diabetes, glycemia in rats in the groups DM SD and DM VitD- was maintained between 300 to 350 mg/dL (P < 0.05). An increase in feed and water consumption and a progressive increase in UAE was observed in all diabetic animals when compared to rats in the Ctrl SD and Ctrl VitD- groups (P < 0.05, respectively). The rats in the DM VitD- group also showed an increase in GFR when compared to the rats in the Ctrl VitD- and the DM SD groups (P < 0.05). The morphometric data demonstrated an increase in the area of the glomerular tuft, fractional mesangial area and tubulointerstitial fibrosis in rats in the DM VitD- group when compared to the Ctrl VitD- and the DM SD groups (P < 0.05). The immunohistochemical studies showed increased the desmin expression in the glomerular edge and cortical and medullary tubulointerstitial vimentin expression in the DM VitD- group when compared to the Ctrl VitD- and the DM SD groups (P < 0.05), important markers of mesenchymal epithelial transition (EMT).

Discussão e Conclusões

The results of the present study showed that compared with the control rats, the diabetic rats with VitD deficiency presented more intense disturbances on the renal function and structure. The effects of its deficiency can accelerate the progression to fibrosis and epithelial transdifferentiation in the renal cells of these animals.

Palavras Chave

diabetic nephropathy, vitamin D deficiency, EMT

Área

Doença renal crônica

Instituições

Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo - Ribeirão Preto - São Paulo - Brasil

Autores

Cláudia Silva Souza, Heloísa Della Colleta Franscecato, Amanda Lima Deluque, Cleonice Giovanni, Francisco Jose Albuquerque de Paula, Roberto Silva Costa, Terezila Machado Coimbra