Comparison of acute kidney injury following brain death between male and female rats

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Tipo de produção
article
Data de publicação
2023
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Título do Volume
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ELSEVIER ESPANA
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CLINICS, v.78, article ID 100222, 8p, 2023
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Background: Clinical reports associate kidneys from female donors with worse prognostic in male recipients. Brain Death (BD) produces immunological and hemodynamic disorders that affect organ viability. Following BD, female rats are associated with increased renal inflammation interrelated with female sex hormone reduction. Here, the aim was to investigate the effects of sex on BD-induced Acute Kidney Injury (AKI) using an Isolated Perfused rat Kidney (IPK) model.Methods: Wistar rats, females, and males (8 weeks old), were maintained for 4h after BD. A left nephrectomy was performed and the kidney was preserved in a cold saline solution (30 min). IPK was performed under normothermic temperature (37 & DEG;C) for 90 min using WME as perfusion solution. AKI was assessed by morphological analyses, staining of complement system components and inflammatory cell markers, perfusion flow, and creatinine clearance. Results: BD-male kidneys had decreased perfusion flow on IPK, a phenomenon that was not observed in the kidneys of BD-females (p < 0.0001). BD-male kidneys presented greater proximal (p = 0.0311) and distal tubule (p = 0.0029) necrosis. However, BD-female kidneys presented higher expression of eNOS (p = 0.0060) and greater upregulation of inflammatory mediators, iNOS (p = 0.0051), and Caspase-3 (p = 0.0099). In addition, both sexes had increased complement system formation (C5b-9) (p=0.0005), glomerular edema (p = 0.0003), and nNOS (p = 0.0051).Conclusion: The present data revealed an important sex difference in renal perfusion in the IPK model, evidenced by a pronounced reduction in perfusate flow and low eNOS expression in the BD-male group. Nonetheless, the upregulation of genes related to the proinflammatory cascade suggests a progressive inflammatory process in BDfemale kidneys.
Palavras-chave
Brain death, Sex differences, Acute kidney injury, Isolated perfused kidney, Rat
Referências
  1. An JN, 2020, J CELL MOL MED, V24, P5640, DOI 10.1111/jcmm.15225
  2. Armstrong-Jr R, 2021, ANN TRANSL MED, V9, DOI 10.21037/atm-21-1408
  3. Armstrong R, 2020, TRANSPL INT, V33, P1312, DOI 10.1111/tri.13687
  4. Avlonitis VS, 2005, AM J TRANSPLANT, V5, P684, DOI 10.1111/j.1600-6143.2005.00755.x
  5. Basile DP, 2012, COMPR PHYSIOL, V2, P1303, DOI 10.1002/cphy.c110041
  6. Bos EM, 2007, KIDNEY INT, V72, P797, DOI 10.1038/sj.ki.5002400
  7. Bouma HR, 2009, AM J TRANSPLANT, V9, P989, DOI 10.1111/j.1600-6143.2009.02587.x
  8. Breithaupt-Faloppa AC, 2016, J SURG RES, V200, P714, DOI 10.1016/j.jss.2015.09.018
  9. Damman J, 2008, TRANSPLANTATION, V85, P923, DOI 10.1097/TP.0b013e3181683cf5
  10. Deitch EA, 2008, J TRAUMA, V65, P566, DOI 10.1097/TA.0b013e31814b2c38
  11. Elmore S, 2007, TOXICOL PATHOL, V35, P495, DOI 10.1080/01926230701320337
  12. Ferreira SG, 2018, INFLAMMATION, V41, P1488, DOI 10.1007/s10753-018-0794-7
  13. Han SJ, 2019, KIDNEY RES CLIN PRAC, V38, P427, DOI 10.23876/j.krcp.19.062
  14. Hernandez D, 2020, KIDNEY BLOOD PRESS R, V45, P1, DOI 10.1159/000504546
  15. Horbelt M, 2007, AM J PHYSIOL-RENAL, V293, pF688, DOI 10.1152/ajprenal.00452.2006
  16. HUBANK M, 1994, NUCLEIC ACIDS RES, V22, P5640, DOI 10.1093/nar/22.25.5640
  17. Huijink TM, 2021, CTS-CLIN TRANSL SCI, V14, P222, DOI 10.1111/cts.12846
  18. Ichimura T, 1998, J BIOL CHEM, V273, P4135, DOI 10.1074/jbc.273.7.4135
  19. Karch J, 2015, CIRC RES, V116, P1800, DOI 10.1161/CIRCRESAHA.116.305421
  20. Kolkert JLP, 2007, LAB ANIM-UK, V41, P363, DOI 10.1258/002367707781282848
  21. Kusaka M, 2000, TRANSPLANTATION, V69, P405, DOI 10.1097/00007890-200002150-00017
  22. Liu CB, 2022, CELL DEATH DISCOV, V8, DOI 10.1038/s41420-022-01032-2
  23. Maggiore U, 2015, NEPHROL DIAL TRANSPL, V30, P217, DOI 10.1093/ndt/gfu212
  24. Molitoris BA, 2014, J CLIN INVEST, V124, P2355, DOI 10.1172/JCI72269
  25. Muller V, 1999, KIDNEY INT, V55, P2011, DOI 10.1046/j.1523-1755.1999.00441.x
  26. Poppelaars F, 2017, MOL IMMUNOL, V84, P77, DOI 10.1016/j.molimm.2016.11.004
  27. Rebolledo RA, 2016, J TRANSL MED, V14, DOI 10.1186/s12967-016-0890-0
  28. Ricardo-da-Silva FY, 2021, TRANSPLANTATION, V105, P775, DOI 10.1097/TP.0000000000003467
  29. Sharawy N, 2013, MICROVASC RES, V85, P118, DOI 10.1016/j.mvr.2012.10.002
  30. Simao RR, 2016, ACTA CIR BRAS, V31, P278, DOI 10.1590/S0102-865020160040000009
  31. Simas R, 2012, CLINICS, V67, P69, DOI 10.6061/clinics/2012(01)11
  32. Van Erp AC, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-22689-9
  33. van Erp AC, 2020, AM J TRANSPLANT, V20, P2425, DOI 10.1111/ajt.15885
  34. Vieira RF, 2020, TRANSPLANTATION, V104, P1862, DOI 10.1097/TP.0000000000003280
  35. Vieira RF, 2018, J HEART LUNG TRANSPL, V37, P1381, DOI 10.1016/j.healun.2018.06.015
  36. Watts RP, 2013, J TRANSPLANT, V2013, DOI 10.1155/2013/521369
  37. Yokoyama Y, 2003, CYTOKINE, V21, P91, DOI 10.1016/S1043-4666(03)00014-0
  38. Yu HP, 2007, ANN SURG, V245, P971, DOI 10.1097/01.sla.0000254417.15591.88
  39. Zuk A, 2016, ANNU REV MED, V67, P293, DOI 10.1146/annurev-med-050214-013407