PMID- 37569342 OWN - NLM STAT- MEDLINE DCOM- 20230814 LR - 20230815 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 15 DP - 2023 Jul 26 TI - Indoxyl Sulfate Administration during Pregnancy Contributes to Renal Injury and Increased Blood-Brain Barrier Permeability. LID - 10.3390/ijms241511968 [doi] LID - 11968 AB - Rates of pregnancy-related acute kidney injury (PR-AKI) have increased in the U.S over the past two decades, but how PR-AKI affects the blood-brain barrier (BBB) is understudied. AKI is associated with increased amounts of uremic toxins, like indoxyl sulfate (I.S), whose chronic administration leads to BBB and cognitive changes. This study's objective was to determine if (1) PR-AKI increases I.S and (2) if administration of I.S during pregnancy elicits renal injury and/or increases BBB permeability. From gestational day (GD) 11 to GD19, Sprague Dawley rats were given either 100 or 200 mg/kg body-weight dose of I.S. PR-AKI was induced on GD18 via 45 min bilateral renal ischemic reperfusion surgery. On GD18, metabolic cage metrics and metabolic waste was collected and on GD19 blood pressure, and BBB permeability (by Evan's Blue infusion) were measured. I.S and creatinine were measured in both urine and circulation, respectively. One-way ANOVA or student t-tests were performed using GraphPad Prism with a p < 0.05 significance. I.S and PR-AKI led to oliguria. I.S administration led to increased BBB permeability compared to normal pregnant and PR-AKI animals. These results suggest that I.S administration during pregnancy leads to increased BBB permeability and evidence of renal injury comparable to PR-AKI animals. FAU - Griffin, Ashley AU - Griffin A AUID- ORCID: 0000-0002-5899-236X AD - Program in Neuroscience, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. FAU - Berry, Brittany AU - Berry B AD - Department of Obstetrics and Gynecology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. FAU - Spencer, Shauna-Kay AU - Spencer SK AD - Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. FAU - Bowles, Teylor AU - Bowles T AD - Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. FAU - Wallace, Kedra AU - Wallace K AUID- ORCID: 0000-0003-4511-0046 AD - Department of Obstetrics and Gynecology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. AD - Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. LA - eng GR - P20 GM121334/GM/NIGMS NIH HHS/United States GR - P20GM121334/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20230726 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - N187WK1Y1J (Indican) SB - IM MH - Rats MH - Pregnancy MH - Animals MH - Female MH - *Blood-Brain Barrier/metabolism MH - Rats, Sprague-Dawley MH - Indican/metabolism MH - Kidney/metabolism MH - *Acute Kidney Injury MH - Permeability PMC - PMC10419049 OTO - NOTNLM OT - acute kidney injury OT - blood-brain barrier OT - indoxyl sulfate COIS- The authors declare no conflict of interest. EDAT- 2023/08/12 10:47 MHDA- 2023/08/14 06:43 PMCR- 2023/07/26 CRDT- 2023/08/12 01:08 PHST- 2023/06/28 00:00 [received] PHST- 2023/07/18 00:00 [revised] PHST- 2023/07/25 00:00 [accepted] PHST- 2023/08/14 06:43 [medline] PHST- 2023/08/12 10:47 [pubmed] PHST- 2023/08/12 01:08 [entrez] PHST- 2023/07/26 00:00 [pmc-release] AID - ijms241511968 [pii] AID - ijms-24-11968 [pii] AID - 10.3390/ijms241511968 [doi] PST - epublish SO - Int J Mol Sci. 2023 Jul 26;24(15):11968. doi: 10.3390/ijms241511968.