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

Feng Li, Edward M. Bahnson, Jennifer Wilder, Robin Siletzky, John Hagaman, Volker Nickekeit, Sylvia Hiller, Azraa Ayesha, Lanfei Feng, Jerrold S. Levine, Nobuyuki Takahashi, Nobuyo Maeda-Smithies

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number101504
JournalRedox Biology
Volume32
DOIs
Publication statusPublished - 2020 May

Keywords

  • Cyanocobalamin
  • Fibrosis
  • Inflammation
  • Ischemia/reperfusion injury
  • Mouse proximal tubular cells
  • Superoxide dismutase mimetic

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

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