Investigating the Reno protective effect of Vitamin D in male mice with sepsis via modulation of PI3K expression

Abstract

Objective: to explore therapeutic efficacy of vitamin D in alleviating sepsis-associated renal dysfunction through modulation of phosphoinositide 3-kinase (PI3K) gene expression. Method: 4 groups of Mus musculus mice (7 animals/ group) were assigned: Sham group: Animals have identical anesthesia and surgical procedures (laparotomy) for same duration as sepsis induction protocol but without performing cecal ligation and puncture (CLP) procedure. Control group: Mice underwent CLP procedure to induce sepsis. Vehicle group: Animals received 10% (v/v) dimethyl sulfoxide as a vehicle control. Vitamin D group: Each mouse received vitamin D (1 µg/kg) administered 30 minutes prior to CLP procedure. Results: compared to vehicle and control groups, sham group exhibited significantly lower tissue levels of TNF-α, IL-6, F2-Isoprostane, caspase-3, and KIM-1. Similarly, vitamin D group showed a marked reduction in inflammatory and oxidative stress markers. This protective effect was associated with modulation of PI3K signaling pathway, which may contribute to attenuation of renal dysfunction during CLP-induced sepsis in male mice. Histopathological analysis demonstrated that vitamin D treatment significantly ameliorated kidney tissue damage. Conclusion: Findings indicate that vitamin D therapy markedly attenuates sepsis-induced renal tissue injury in adult male mice. This protective effect appears from its pleiotropic actions, including anti-inflammatory, antioxidant, and anti-apoptotic properties. By upregulating PI3K gene expression in renal tissues, vitamin D contributes to prevention of necrosis and apoptosis, highlighting its potential as a therapeutic strategy for mitigating renal dysfunction during sepsis.