Vitamin B12 Protects Against Hypoxia/ Reperfusion Injury in Mouse Proximal Tubule Cells

Acute kidney injury (AKI) is a common syndrome characterized by a sudden decline in kidney function that can potentially lead to death. Ischemia/reperfusion injury (IRI) is the leading cause of AKI and is inevitable during kidney transplants. There is no effective treatment available to treat IRI. Pathways involved in IRI are evidenced to lead to reactive oxygen species (ROS), inflammation, fibrosis, apoptosis, DNA damage response (DDR) and autophagy. Vitamin B12 (B12) or cobalamin, is essential for the human body and is pharmacologically known to scavenge ROS, suppressing inflammation and reverse impaired autophagy that occurs in B12 deficient conditions. To test whether B12 has beneficial effects in IRI, I subjected cultured mouse proximal tubule cells (BU.MPT) to a hypoxia/reperfusion (H/R) procedure and measured transcription of markers for inflammation (Mcp1, Il6, Nos2) and fibrosis (fibronectin), protein markers for apoptosis(Tgf1, c-cap3), and DDR (p.H2AX) induced by hypoxia/reperfusion (H/R). Presence of B12 during the H/R procedure at 0.3µM dramatically inhibited the upregulation of these markers studied and to an increased cell survival. Together, my findings suggest that B12 is a highly promising molecule to prevent/treat AKI.Bachelor of Science in Public Healt