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

• Published in: Molecular biology reports Vol. 46; no. 2; pp. 2197 - 2207
• Main Authors: Lemos, Natália Emerim, Dieter, Cristine, Carlessi, Rodrigo, Rheinheimer, Jakeline, Brondani, Letícia de Almeida, Leitão, Cristiane Bauermann, Bauer, Andrea Carla, Crispim, Daisy
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-04-2019; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Apoptosis; Biomedical and Life Sciences; Biopsy; Brain death; Central nervous system; Creatinine; Genes; Histology; Kidney transplants; Kidneys; Life Sciences; Mitochondrial uncoupling protein 2; Morphology; Original Article; Oxidative stress; Superoxide dismutase; Transplantation; Tumor necrosis factor; Urea; Renal tissue; Brain death; Kidney transplantation; Exendin-4
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-019-04674-1

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
.