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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Pyrrolidine dithiocarbamate reduces alloxan-induced kidney damage by decreasing nox4, inducible nitric oxide synthase, and metalloproteinase-2

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Autor(es):
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Pereira, Bruna Pinheiro [1] ; do Valle, Gabriel Tavares [2] ; Correa Salles, Bruno Cesar [3] ; Mancini Costa, Karla Cristinne [1] ; Angelo, Marilene Lopes [1] ; Lobo Torres, Larissa Helena [1] ; Novaes, Romulo Dias [4] ; Ruginsk, Silvia Graciela [5] ; Tirapelli, Carlos Renato [2] ; de Araujo Paula, Fernanda Borges [3] ; Ceron, Carla Speroni [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Fed Alfenas UNIFAL MG, Dept Alimentos & Medicamentos, Alfenas, MG - Brazil
[2] Univ Sao Paulo, EERP, Sao Paulo - Brazil
[3] Univ Fed Alfenas UNIFAL MG, Dept Anal Clin, Alfenas, MG - Brazil
[4] Univ Fed Alfenas UNIFAL MG, Dept Biol Estrutural, Alfenas, MG - Brazil
[5] Univ Fed Alfenas UNIFAL MG, Dept Ciencias Fisiol, Alfenas, MG - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. 393, n. 10 MAY 2020.
Citações Web of Science: 0
Resumo

We examined the effect of the NF kappa B inhibitor pyrrolidine-1-carbodithioic acid (PDTC) on inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2) activity, and oxidative and inflammatory kidney damage in alloxan-induced diabetes. Two weeks after diabetes induction (alloxan-130 mg/kg), control and diabetic rats received PDTC (100 mg/kg) or vehicle for 8 weeks. Body weight, glycemia, urea, and creatinine were measured. Kidney changes were measured in hematoxylin/eosin sections and ED1 by immunohistochemistry. Kidney thiobarbituric acid reactive substances (TBARS), superoxide anion (O2-), and nitrate/nitrite (NOx) levels, and catalase and superoxide dismutase (SOD) activities were analyzed. Also, kidney nox4 and iNOS expression, and NFkB nuclear translocation were measured by western blot, and MMP-2 by zymography. Glycemia and urea increased in alloxan rats, which were not modified by PDTC treatment. However, PDTC attenuated kidney structural alterations and macrophage infiltration in diabetic rats. While diabetes increased both TBARS and O-2(-) levels, PDTC treatment reduced TBARS in diabetic and O-2(-) in control kidneys. A decrease in NOx levels was found in diabetic kidneys, which was prevented by PDTC. Diabetes reduced catalase activity, and PDTC increased catalase and SOD activities in both control and diabetic kidneys. PDTC treatment reduced MMP-2 activity and iNOS and p65 NF kappa B nuclear expression found increased in diabetic kidneys. Our results show that the NF kappa B inhibitor PDTC reduces renal damage through reduction of Nox4, iNOS, macrophages, and MMP-2 in the alloxan-induced diabetic model. These findings suggest that PDTC inhibits alloxan kidney damage via antioxidative and anti-inflammatory mechanisms. (AU)

Processo FAPESP: 15/22046-8 - Participação dos receptores AT1 no aumento da pressão arterial e do estresse oxidativo vascular induzidos pela abstinência ao etanol
Beneficiário:Carlos Renato Tirapelli
Modalidade de apoio: Auxílio à Pesquisa - Regular