Effects of different routes and forms of Vitamin D administration on septic acute kidney injury in obese mice

Sepsis-associated acute kidney injury (S-AKI) is a common complication of most critically-ill patients characterized by excessive inflammation, oxidative stress and immunosuppression. Meanwhile, obesity is a condition that impairs immune responses and aggravates inflammation in sepsis. Vit D is a nutrient that has extraskeletal functions such as immune regulation and anti-inflammation. This study examined the effects of different routes and forms of vit D administration on S-AKI in obese mice. Male C57BL/6 mice were fed a high-fat diet for 8-10 weeks and divided into four different treatment groups: without vitD (S), with oral Cholecalciferol 1 day before sepsis (G), with intravenous Calcitriol 1h after sepsis (V), and with both Cholecalciferol before and intravenous Calcitriol after sepsis (GV). Sepsis was induced by Cecal ligation and puncture (CLP) to mimic polymicrobial peritonitis. Mice were sacrificed at 12 and 24h after sepsis. The expression of inflammatory markers such as TLR4, NF-B, IL-6, TNF-, MCP1 , MDA levels and MPO activity were downregulated while Th1/Th2 ratio increased and Th17/Treg ratio decreased simultaneously in the GV group at 24h followed by the V group in which the expression of Caspase 3 decreased while Th1/Th2 ratio increased and Th17/Treg ratio decreased concurrently at 24h. The findings suggest that vit D could ameliorate inflammation and modulate immunity, which may attenuate S-AKI in obese mice, especially when administered both orally and intravenously.