Protective Effect of Empagliflozin from Acute Renal Injury During Endotoxemia in Mice Model

Abstract

One of the most complex clinical challenges facing medical practice is sepsis-induced renal dysfunction, which results from polymicrobial sepsis and despite many therapeutic approaches have been used
in such clinical challenges, still there is more need for a new effective therapeutic approach. This study investigated the potential protective effect of empagliflozin from acute renal injury during endotoxemia in mice.
24 adult male Swiss-albino mice aged 8-12 weeks, with a weight of 20-37 g, were randomized into 4 equal
groups (n = 6), sham (laparotomy without CLP), sepsis (laparotomy with CLP), vehicle (equivalent volume
of DMSO prior to CLP), empagliflozin (10 mg/kg/day i.p prior to CLP) group. Blood sample used to assessment serum levels of urea and creatinine. Kidney used to assessed tissue TNF-α, IL-10, IL-6, TNFR1, TLR4
and TLR2 as well as the histological examination. Serum levels of urea, creatinine and tissue levels of TNF-α,
IL-6, IL-10, and TNFR1 in sham group are significantly lowered than those in sepsis and vehicle groups. In
addition, the serum levels of these parameters in empagliflozin group are significantly lowered than those
of sepsis and vehicle groups, otherwise IL-10 in empagliflozin group are significantly increase than those of
sepsis and vehicle groups. On the other hand, it showed that the tissue levels of TLR4 and TLR2 in sham
group are significantly lowered than those in both sepsis and vehicle groups. Also, these parameters are
significantly lowered in empagliflozin group than those of both sepsis and vehicle groups. In histopathology
examination, the empagliflozin significantly reduce the kidney injury, minimize the severity of tubular damage and inflammation in comparison with sepsis and vehicle groups that showed severe renal injury, tubular
damage and inflammation. Empagliflozin has the ability to attenuate renal dysfunction during CLP-induced
polymicrobial sepsis through his modulating effects on TLR4 and TLR2 downstream signaling pathways
including NF-κB cascades, and subsequently decreased proinflammatory cytokines (TNF-α, IL-6) and the
TNFR1 and increase anti-inflammatory cytokine (IL-10)