Pyrrolidine dithiocarbamate reduces alloxan-induced kidney damage by decreasing nox4, inducible nitric oxide synthase, and metalloproteinase-2
| العنوان: | Pyrrolidine dithiocarbamate reduces alloxan-induced kidney damage by decreasing nox4, inducible nitric oxide synthase, and metalloproteinase-2 |
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| المؤلفون: | Carlos R. Tirapelli, Gabriel Tavares do Valle, Silvia Graciela Ruginsk, Carla S. Ceron, Fernanda Borges de Araújo Paula, Larissa Helena Torres, Marilene Lopes Ângelo, Karla Cristinne Mancini Costa, Rômulo Dias Novaes, Bruna Pinheiro Pereira, Bruno Cesar Correa Salles |
| المصدر: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Pyrrolidines, Nitric Oxide Synthase Type II, Matrix Metalloproteinase Inhibitors, 030204 cardiovascular system & hematology, medicine.disease_cause, Antioxidants, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pyrrolidine dithiocarbamate, Thiocarbamates, Internal medicine, Alloxan, medicine, TBARS, Animals, Rats, Wistar, Pharmacology, Kidney, ESTRESSE OXIDATIVO, biology, Reduced catalase activity, Chemistry, General Medicine, Rats, Nitric oxide synthase, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, NADPH Oxidase 4, biology.protein, Matrix Metalloproteinase 2, Kidney Diseases, Oxidative stress |
| الوصف: | We examined the effect of the NFκB 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 O2− levels, PDTC treatment reduced TBARS in diabetic and O2− 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 NFκB nuclear expression found increased in diabetic kidneys. Our results show that the NFκB 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. |
| تدمد: | 1432-1912 0028-1298 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5c551479cedf0714ae38dc26c57b7c5f https://doi.org/10.1007/s00210-020-01906-1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5c551479cedf0714ae38dc26c57b7c5f |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14321912 00281298 |
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