TY - JOUR
T1 - Oral high dose vitamin B12 decreases renal superoxide and post-ischemia/reperfusion injury in mice
AU - Li, Feng
AU - Bahnson, Edward M.
AU - Wilder, Jennifer
AU - Siletzky, Robin
AU - Hagaman, John
AU - Nickekeit, Volker
AU - Hiller, Sylvia
AU - Ayesha, Azraa
AU - Feng, Lanfei
AU - Levine, Jerrold S.
AU - Takahashi, Nobuyuki
AU - Maeda-Smithies, Nobuyo
N1 - Funding Information:
This work was supported by a grant from the National Institutes of Health ( R01HL049277 to N.M-S and K01HL145354 to E.M.B.) The histology core facility at UNC is supported by NIH Grant DK 034987 .
Publisher Copyright:
© 2020 The Authors
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - Cyanocobalamin
KW - Fibrosis
KW - Inflammation
KW - Ischemia/reperfusion injury
KW - Mouse proximal tubular cells
KW - Superoxide dismutase mimetic
UR - http://www.scopus.com/inward/record.url?scp=85081344795&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081344795&partnerID=8YFLogxK
U2 - 10.1016/j.redox.2020.101504
DO - 10.1016/j.redox.2020.101504
M3 - Article
C2 - 32182573
AN - SCOPUS:85081344795
VL - 32
JO - Redox Biology
JF - Redox Biology
SN - 2213-2317
M1 - 101504
ER -