Oral high dose vitamin B12 decreases renal superoxide and post-ischemia/reperfusion injury in mice
Authors: John Hagaman
Jennifer Wilder
Robin Siletzky
Sylvia Hiller
Lanfei Feng
Feng Li
Edward M Bahnson
Jerrold S Levine
Azraa Ayesha
Volker Nickekeit
Nobuyuki Takahashi
Nobuyo Maeda-Smithies
Journal: Redox Biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cyanocobalamin; Fibrosis; Inflammation; Ischemia/reperfusion injury; Mouse proximal tubular cells
Affiliations: Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA. Electronic address: ., Department of Surgery, The University of North Carolina, Chapel Hill, NC, 27599, USA., Dept of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC, 27599, USA., 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., Section of Nephrology, Department of Medicine, University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center, Chicago, IL, 60612, USA., 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.

Abstract:  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. 

Retracted: No

PubPeer comments:
 The images in Figure 5A and 5B appear to be the same. *** ![file] , 
 #1 My goodness, I did not notice at all! We take issues of data integrity seriously. When I was assembling the figures, I must have inserted panel B twice by mistake. Because no pH2A-immunostained nuclei were detectable in kidneys of sham-operated mice either with or without B12 treatment, it escaped my attention, as well as my coauthorsu2019, completely. I have remade the Figure 5 by replacing with a correct representation of panel A as attached below, and am contacting the Journal to correct the Figure 5 as a corrigendum. While this mistake does not influence our conclusion, I am very concerned and will do my best to have this corrected by the journal as well as to prevent similar mistakes in the future. I thank you very much for noticing our error. ![file] , 
 May 31, 2021 The authors regret that an error was made, in Fig. 5, the panel A and panel B are identical. Below is the correct Figure 5. ![file] The authors would like to apologise for any inconvenience caused. , 
 #3 This is a year ago. , 
 #4 Yes. I was posting the correction here for the convenience of readers. , 
 #4 Thank you!! ,