PMID- 37942539 OWN - NLM STAT- MEDLINE DCOM- 20231221 LR - 20240208 IS - 1522-1466 (Electronic) IS - 1522-1466 (Linking) VI - 326 IP - 1 DP - 2024 Jan 1 TI - Acute high-dose MitoQ does not increase urinary kidney injury markers in healthy adults: a randomized crossover trial. PG - F135-F142 LID - 10.1152/ajprenal.00186.2023 [doi] AB - Several human studies have used the mitochondrial antioxidant MitoQ. Recent in vitro data indicating that MitoQ may induce nephrotoxicity caused concern regarding the safety of MitoQ on the kidneys, but the doses were supraphysiological. Therefore, we sought to determine whether acute MitoQ elicits changes in urinary biomarkers associated with tubular injury in healthy adults with our hypothesis being there would be no changes. Using a randomized crossover design, 32 healthy adults (16 females and 16 males, 29 +/- 11 yr old) consumed MitoQ (100-160 mg based on body mass) or placebo capsules. We obtained serum samples and a 4- to 6-h postcapsule consumption urine sample. We assessed creatinine clearance and urine kidney injury biomarkers including the chitinase 3-like-1 gene product YKL-40, kidney-injury marker-1, monocyte chemoattractant protein-1, epidermal growth factor, neutrophil gelatinase-associated lipocalin, interleukin-18, and uromodulin using multiplex assays. We used t tests, Wilcoxon tests, and Hotelling's T(2) to assess global differences in urinary kidney injury markers between conditions. Acute MitoQ supplementation did not influence urine flow rate (P = 0.086, r(rb) = 0.39), creatinine clearance (P = 0.085, r(rb) = 0.42), or urinary kidney injury markers (T(2)(2,8) = 30.6, P = 0.121, univariate ps > 0.064). Using exploratory univariate analysis, MitoQ did not alter individual injury markers compared with placebo (e.g., placebo vs. MitoQ: YKL-40, 507 +/- 241 vs. 442 +/- 236 pg/min, P = 0.241; kidney injury molecule-1, 84.1 +/- 43.2 vs. 76.2 +/- 51.2 pg/min, P = 0.890; and neutrophil gelatinase-associated lipocalin, 10.8 +/- 10.1 vs. 9.83 +/- 8.06 ng/min, P = 0.609). In conclusion, although longer-term surveillance and data are needed in clinical populations, our findings suggest that acute high-dose MitoQ had no effect on urinary kidney injury markers in healthy adults.NEW & NOTEWORTHY We found acute high-dose mitochondria-targeted antioxidant (MitoQ) supplementation was not nephrotoxic and had no effect on markers of acute kidney injury in healthy adults. These findings can help bolster further confidence in the safety of MitoQ, particularly for future investigations seeking to examine the role of mitochondrial oxidative stress, via acute MitoQ supplementation, on various physiological outcomes. FAU - Linder, Braxton A AU - Linder BA AUID- ORCID: 0000-0001-6825-5622 AD - School of Kinesiology, Auburn University, Auburn, Alabama, United States. FAU - Stute, Nina L AU - Stute NL AUID- ORCID: 0000-0001-8213-638X AD - School of Kinesiology, Auburn University, Auburn, Alabama, United States. FAU - Hutchison, Zach J AU - Hutchison ZJ AUID- ORCID: 0000-0001-9091-5973 AD - School of Kinesiology, Auburn University, Auburn, Alabama, United States. FAU - Barnett, Alex M AU - Barnett AM AD - School of Kinesiology, Auburn University, Auburn, Alabama, United States. FAU - Tharpe, McKenna A AU - Tharpe MA AUID- ORCID: 0000-0002-3868-1564 AD - School of Kinesiology, Auburn University, Auburn, Alabama, United States. FAU - Kavazis, Andreas N AU - Kavazis AN AUID- ORCID: 0000-0002-2535-7490 AD - School of Kinesiology, Auburn University, Auburn, Alabama, United States. FAU - Kirkman, Danielle L AU - Kirkman DL AUID- ORCID: 0000-0003-1648-0662 AD - Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, Virginia, United States. FAU - Gutierrez, Orlando M AU - Gutierrez OM AUID- ORCID: 0000-0001-6593-3571 AD - Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States. FAU - Robinson, Austin T AU - Robinson AT AUID- ORCID: 0000-0001-8250-3952 AD - School of Kinesiology, Auburn University, Auburn, Alabama, United States. LA - eng GR - R15 HL165325/HL/NHLBI NIH HHS/United States GR - K01 HL147998/HL/NHLBI NIH HHS/United States GR - UL1 TR003096/TR/NCATS NIH HHS/United States GR - P30 DK079337/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20231109 PL - United States TA - Am J Physiol Renal Physiol JT - American journal of physiology. Renal physiology JID - 100901990 RN - 0 (Lipocalin-2) RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (Antioxidants) RN - AYI8EX34EU (Creatinine) RN - 47BYS17IY0 (mitoquinone) RN - 0 (Biomarkers) SB - IM MH - Male MH - Adult MH - Female MH - Humans MH - Lipocalin-2/metabolism MH - Cross-Over Studies MH - Chitinase-3-Like Protein 1/metabolism MH - *Antioxidants/metabolism MH - Creatinine/metabolism MH - Kidney/metabolism MH - *Acute Kidney Injury/chemically induced/diagnosis MH - Biomarkers/urine OTO - NOTNLM OT - acute kidney injury OT - cardiovascular disease OT - chronic kidney disease OT - dietary antioxidants OT - mitochondrial reactive oxygen species EDAT- 2023/11/09 06:42 MHDA- 2023/12/21 06:43 CRDT- 2023/11/09 04:33 PHST- 2023/12/21 06:43 [medline] PHST- 2023/11/09 06:42 [pubmed] PHST- 2023/11/09 04:33 [entrez] AID - 10.1152/ajprenal.00186.2023 [doi] PST - ppublish SO - Am J Physiol Renal Physiol. 2024 Jan 1;326(1):F135-F142. doi: 10.1152/ajprenal.00186.2023. Epub 2023 Nov 9.