Nephroprotective Effect of Melatonin in Sepsis Induces Renal Injury: CLP Mice Model

Abstract

One of the most complex clinical challenges in medical practice is sepsis-induced renal dysfunction and despite many therapeutic approaches have been used in such clinical challenges, still there is more
need for a new effective therapeutic approach. The objectives were to investigate if melatonin may help protect the kidneys during polymicrobial sepsis by modulating the inflammatory and oxidative stress pathways.
Twenty four mature male Swiss-albino mice with were randomized into 4 groups (n = 6), sham (laparotomy
without CLP), sepsis (laparotomy with CLP), vehicle (equivalent volume of DMSO prior to CLP), melatonin
(30 mg/kg/30 min i.p prior to CLP and 30 min, 4 h, and 8 h after 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, VEGF,
notch1and jagged1 in addition to the histology analysis. Blood levels of urea and creatinine, as well as tissue
levels of TNF-, IL-6, IL-10, VEGF, and TNFR1, were much lower in sham group as compared to sepsis and
vehicle groups. Furthermore, blood levels of urea and creatinine, as well as tissue levels of TNF-, IL-6, VEGF,
and TNFR1, were considerably lower in melatonin group in comparison to the sepsis and vehicle groups,
while IL-10 is significantly hiegher in melatonin group in comparison to the sepsis and vehicle groups. But,
It had been discovered that the tissue levels of notch1 and jagged1 in the sham group were much lower than
those in the sepsis and vehicle groups. Furthermore, it was discovered that the tissue levels of notch1 and
jagged1 in melatonin group were much lower in comparison to those in the sepsis and vehicle groups. In histology, melatonin may dramatically decrease renal injury and decrease the severity of tubular damage and
inflammation when compared to the sepsis and vehicle groups, which had severe renal impairment, tubular
damage, and inflammation. Melatonin can reduce renal impairment during CLP-induced polymicrobial
sepsis in male mice by altering notch1 and jagged1 downstream signaling pathways, resulting in reduced
cytokines IL6, TNF, VEGF, and the TNFR1 and increased anti-inflammatory cytokine (IL-10).