Oral high dose vitamin B12 decreases renal superoxide and post-ischemia/reperfusion injury in mice.

Autor:	Li F; Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA. Electronic address: lif@med.unc.edu., Bahnson EM; Department of Surgery, The University of North Carolina, Chapel Hill, NC, 27599, USA., Wilder J; Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA., Siletzky R; Department of Surgery, The University of North Carolina, Chapel Hill, NC, 27599, USA., Hagaman J; Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA., Nickekeit V; Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA; Division of Nephropathy, School of Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA., Hiller S; Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA., Ayesha A; Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA., Feng L; Section of Nephrology, Department of Medicine, University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center, Chicago, IL, 60612, USA., Levine JS; Section of Nephrology, Department of Medicine, University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center, Chicago, IL, 60612, USA., Takahashi N; Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA; Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School, Sendai, Japan., Maeda-Smithies N; Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2020 May; Vol. 32, pp. 101504. Date of Electronic Publication: 2020 Mar 10.
DOI:	10.1016/j.redox.2020.101504
Abstrakt:	Renal ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), a potentially fatal syndrome characterized by a rapid decline in kidney function. Excess production of superoxide contributes to the injury. We hypothesized that oral administration of a high dose of vitamin B12 (B12 - cyanocobalamin), which possesses a superoxide scavenging function, would protect kidneys against IRI and provide a safe means of treatment. Following unilateral renal IR surgery, C57BL/6J wild type (WT) mice were administered B12 via drinking water at a dose of 50 mg/L. After 5 days of the treatment, plasma B12 levels increased by 1.2-1.5x, and kidney B12 levels increased by 7-8x. IRI mice treated with B12 showed near normal renal function and morphology. Further, IRI-induced changes in RNA and protein markers of inflammation, fibrosis, apoptosis, and DNA damage response (DDR) were significantly attenuated by at least 50% compared to those in untreated mice. Moreover, the presence of B12 at 0.3 μM in the culture medium of mouse proximal tubular cells subjected to 3 hr of hypoxia followed by 1 hr of reperfusion in vitro showed similar protective effects, including increased cell viability and decreased reactive oxygen species (ROS) level. We conclude that a high dose of B12 protects against perfusion injury both in vivo and in vitro without observable adverse effects in mice and suggest that B12 merits evaluation as a treatment for I/R-mediated AKI in humans. Competing Interests: Declaration of competing interest None. (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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