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Molecular Biology Reports

, Volume 46, Issue 2, pp 2197–2207 | Cite as

Renal effects of exendin-4 in an animal model of brain death

  • Natália Emerim Lemos
  • Cristine Dieter
  • Rodrigo Carlessi
  • Jakeline Rheinheimer
  • Letícia de Almeida Brondani
  • Cristiane Bauermann Leitão
  • Andrea Carla Bauer
  • Daisy CrispimEmail author
Original Article
  • 118 Downloads

Abstract

Organ transplantation is the gold standard therapy for the majority of patients with terminal organ failure. However, it is still a limited treatment especially due to the low number of brain death (BD) donors in relation to the number of waiting list recipients. Strategies to increase the quantity and quality of donor organs have been studied, and the administration of exendin-4 (Ex-4) to the donor may be a promising approach. Male Wistar rats were randomized into 3 groups: (1) control, without central nervous system injury; (2) BD induced experimentally, and (3) BD induced experimentally + Ex-4 administered immediately after BD induction. After BD induction, animals were monitored for 6 h before blood collection and kidney biopsy. Kidney function was assessed by biochemical quantification of plasma kidney markers. Gene and protein expressions of inflammation- and stress-related genes were evaluated by RT-qPCR and immunoblot analysis. Animals treated with Ex-4 had lower creatinine and urea levels compared with controls. BD induced oxidative stress in kidney tissue through increased expression of Ucp2, Sod2 and Inos, and Ex-4 administration reduced the expression of these genes. Ex-4 also induced increased expression of the anti-apoptotic Bcl2 gene. Nlrp3 and Tnf expressions were up-regulated in the BD group compared with controls, but Ex-4 treatment had no effect on these genes. Our findings suggest that Ex-4 administration in BD rats reduces BD-induced kidney damage by decreasing the expression of oxidative stress genes and increasing the expression of Bcl2.

Keywords

Brain death Kidney transplantation Renal tissue Exendin-4 

Notes

Funding

This study was partially supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundo de Incentivo à Pesquisa e Eventos (FIPE) at the Hospital de Clínicas de Porto Alegre, Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). D.C. and C.B.L. are recipients of scholarships from CNPq.

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Laboratory of Human Pancreatic Islet Biology, Endocrine DivisionHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  2. 2.Postgraduation Program in Medical Sciences: Endocrinology, Faculdade de MedicinaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.School of Biomedical Sciences, Curtin Health Innovation Research InstituteCurtin UniversityBentley, PerthAustralia
  4. 4.Nephrology DivisionHospital de Clínicas de Porto AlegrePorto AlegreBrazil

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