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Nanocurcumin combined with insulin alleviates diabetic kidney disease through P38/P53 signaling axis.
Ganugula, Raghu; Nuthalapati, Nikhil K; Dwivedi, Subhash; Zou, Dianxiong; Arora, Meenakshi; Friend, Richard; Sheikh-Hamad, David; Basu, Rita; Kumar, M N V Ravi.
Afiliação
  • Ganugula R; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA; College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA; Alabama Life Research Ins
  • Nuthalapati NK; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA; College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA.
  • Dwivedi S; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA; College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA.
  • Zou D; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA; College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA.
  • Arora M; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA; College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA; Alabama Life Research Ins
  • Friend R; College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA.
  • Sheikh-Hamad D; Division of Nephrology and Selzman Institute for Kidney Health, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases, Michael E. Debakey Veterans Affairs Medical Center, Houston, TX, USA.
  • Basu R; Division of Endocrinology, Center of Diabetes Technology, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Kumar MNVR; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA; College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA; Alabama Life Research Ins
J Control Release ; 353: 621-633, 2023 01.
Article em En | MEDLINE | ID: mdl-36503070
Treatments for diabetic kidney disease (DKD) mainly focus on managing hyperglycemia and hypertension, but emerging evidence suggests that inflammation also plays a role in the pathogenesis of DKD. This 10-week study evaluated the efficacy of daily oral nanoparticulate-curcumin (nCUR) together with long-acting insulin (INS) to treat DKD in a rodent model. Diabetic rats were dosed with unformulated CUR alone, nCUR alone or together with INS, or INS alone. The progression of diabetes was reflected by increases in plasma fructosamine, blood urea nitrogen, creatinine, bilirubin, ALP, and decrease in albumin and globulins. These aberrancies were remedied by nCUR+INS or INS but not by CUR or nCUR. Kidney histopathological results revealed additional abnormalities characteristic of DKD, such as basement membrane thickening, tubular atrophy, and podocyte cytoskeletal impairment. nCUR and nCUR+INS mitigated these lesions, while CUR and INS alone were far less effective, if not ineffective. To elucidate how our treatments modulated inflammatory signaling in the liver and kidney, we identified hyperactivation of P38 (MAPK) and P53 with INS and CUR, whereas nCUR and nCUR+INS deactivated both targets. Similarly, the latter interventions led to significant downregulation of renal NLRP3, IL-1ß, NF-ĸB, Casp3, and MAPK8 mRNA, indicating a normalization of inflammasome and apoptotic pathways. Thus, we show therapies that reduce both hyperglycemia and inflammation may offer better management of diabetes and its complications.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Experimental / Nefropatias Diabéticas / Hiperglicemia Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Control Release Assunto da revista: FARMACOLOGIA Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Experimental / Nefropatias Diabéticas / Hiperglicemia Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Control Release Assunto da revista: FARMACOLOGIA Ano de publicação: 2023 Tipo de documento: Article