PMID- 34769064 OWN - NLM STAT- MEDLINE DCOM- 20211214 LR - 20211214 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 21 DP - 2021 Oct 27 TI - ATRvD1 Attenuates Renal Tubulointerstitial Injury Induced by Albumin Overload in Sepsis-Surviving Mice. LID - 10.3390/ijms222111634 [doi] LID - 11634 AB - Novel strategies for the prevention and treatment of sepsis-associated acute kidney injury and its long-term outcomes have been required and remain a challenge in critical care medicine. Therapeutic strategies using lipid mediators, such as aspirin-triggered resolvin D1 (ATRvD1), can contribute to the resolution of acute and chronic inflammation. In this study, we examined the potential effect of ATRvD1 on long-term kidney dysfunction after severe sepsis. Fifteen days after cecal ligation and puncture (CLP), sepsis-surviving BALB/c mice were subjected to a tubulointerstitial injury through intraperitoneal injections of bovine serum albumin (BSA) for 7 days, called the subclinical acute kidney injury (subAKI) animal model. ATRvD1 treatment was performed right before BSA injections. On day 22 after CLP, the urinary protein/creatinine ratio (UPC), histologic parameters, fibrosis, cellular infiltration, apoptosis, inflammatory markers levels, and mRNA expression were determined. ATRvD1 treatment mitigated tubulointerstitial injury by reducing proteinuria excretion, the UPC ratio, the glomerular cell number, and extracellular matrix deposition. Pro-fibrotic markers, such as transforming growth factor beta (TGFbeta), type 3 collagen, and metalloproteinase (MMP)-3 and -9 were reduced after ATRvD1 administration. Post-septic mice treated with ATRvD1 were protected from the recruitment of IBA1(+) cells. The interleukin-1beta (IL-1beta) levels were increased in the subAKI animal model, being attenuated by ATRvD1. Tumor necrosis factor-alpha (TNF-alpha), IL-10, and IL-4 mRNA expression were increased in the kidney of BSA-challenged post-septic mice, and it was also reduced after ATRvD1. These results suggest that ATRvD1 protects the kidney against a second insult such as BSA-induced tubulointerstitial injury and fibrosis by suppressing inflammatory and pro-fibrotic mediators in renal dysfunction after sepsis. FAU - Silva, Jose Bruno N F AU - Silva JBNF AUID- ORCID: 0000-0003-4398-3943 AD - Institute of Microbiology Paulo de Goes (IMPG), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil. FAU - Calcia, Thayanne B B AU - Calcia TBB AUID- ORCID: 0000-0001-7641-2915 AD - Institute of Biophysics Carlos Chagas Filho (IBCCF), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil. FAU - Silva, Cyntia P AU - Silva CP AD - Institute of Biomedical Sciences (ICB), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil. FAU - Guilherme, Rafael F AU - Guilherme RF AD - Institute of Microbiology Paulo de Goes (IMPG), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil. FAU - Almeida-Souza, Fernando AU - Almeida-Souza F AUID- ORCID: 0000-0003-0047-6159 AD - Laboratory of Immunomodulation and Protozoology, Oswaldo Cruz Institute (IOC), Fiocruz, Rio de Janeiro 21040-900, Brazil. AD - Postgraduate in Animal Science, State University of Maranhao, Sao Luis 65055-310, Brazil. FAU - Lemos, Felipe S AU - Lemos FS AD - Institute of Biomedical Sciences (ICB), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil. FAU - Calabrese, Katia S AU - Calabrese KS AD - Laboratory of Immunomodulation and Protozoology, Oswaldo Cruz Institute (IOC), Fiocruz, Rio de Janeiro 21040-900, Brazil. FAU - Caruso-Neves, Celso AU - Caruso-Neves C AUID- ORCID: 0000-0002-2415-7753 AD - Institute of Biophysics Carlos Chagas Filho (IBCCF), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil. FAU - Neves, Josiane S AU - Neves JS AD - Institute of Biomedical Sciences (ICB), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil. FAU - Benjamim, Claudia F AU - Benjamim CF AD - Institute of Biophysics Carlos Chagas Filho (IBCCF), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil. LA - eng GR - E-26/210.870/2019/FAPERJ/ GR - E-26/202.834/2018/FAPERJ/ GR - 311905/2019-6/CNPq/ PT - Journal Article DEP - 20211027 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Albumins) RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (RNA, Messenger) RN - 0 (resolvin D1) RN - 25167-62-8 (Docosahexaenoic Acids) RN - R16CO5Y76E (Aspirin) SB - IM MH - Acute Kidney Injury/chemically induced/*drug therapy MH - Albumins/pharmacology MH - Animals MH - Aspirin/*pharmacology MH - Biomarkers/metabolism MH - Cytokines/metabolism MH - Disease Models, Animal MH - Docosahexaenoic Acids/*pharmacology MH - Female MH - Inflammation/drug therapy/metabolism MH - Kidney Function Tests/methods MH - Kidney Glomerulus/*drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Proteinuria/chemically induced/drug therapy/metabolism MH - RNA, Messenger/metabolism MH - Sepsis/*drug therapy/metabolism PMC - PMC8583751 OTO - NOTNLM OT - ATRvD1 OT - inflammation OT - kidney OT - renal tubulointerstitial injury OT - resolvin OT - sepsis COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2021/11/14 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/10/27 CRDT- 2021/11/13 01:04 PHST- 2021/07/19 00:00 [received] PHST- 2021/10/15 00:00 [revised] PHST- 2021/10/22 00:00 [accepted] PHST- 2021/11/13 01:04 [entrez] PHST- 2021/11/14 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/10/27 00:00 [pmc-release] AID - ijms222111634 [pii] AID - ijms-22-11634 [pii] AID - 10.3390/ijms222111634 [doi] PST - epublish SO - Int J Mol Sci. 2021 Oct 27;22(21):11634. doi: 10.3390/ijms222111634.