Assessment of Sumatriptan on Sepsis-Induced Kidney injury in the Cecal Ligation and Puncture Mice Model

Sepsis is a severe systemic inflammatory response with high mortality rate resulting from different microorganisms. Cytokines activation is essential for the immune response, but in painful conditions like sepsis, cytokines act as a double-edged sword and dysregulate immune response which is life-threatening owing to multiple organ dysfunction. The abnormality in 5-HT function is involved in pathological conditions like irritable bowel syndrome, inflammation, myocardial ischemia, itch and renal injury. Sumatriptan, a 5-HT1B/ 1D agonist, has anti-inflammatory and anti-oxidative stress effects on animal models. This study was aimed to assess the effects of sumatriptan on kidney injury, the levels of pro-inflammatory cytokines and the percentage of survival in (CLP)-induced sepsis were examined. Cecal ligation and puncture (CLP) model was done on adult C57BL/6 male mice to induce Polymicrobial sepsis. Sumatriptan was injected intraperitoneally 1 h after the sepsis induction by CLP at doses of 0.1, 0.3, and 1 mg/kg in 3 treatment groups. To study the effect of sumatriptan on short-term survival, septic animals were detected 72 h after CLP. Serum levels of TNF-alpha, IL-1 beta, IL-6 and IL-10 were evaluated. To study sepsis-induced acute renal failure, kidney functional biomarkers and histopathological alterations were evaluated. Sumatriptan (0.3 mg/kg) administration significantly enhanced survival rate (P < 0.01) compared to the CLP group. The beneficial effects of sumatriptan were related to a significant decrease in the pro-inflammatory cytokines and elevated level of IL-10. Sumatriptan presented protective effects on kidney biomarkers and histopathology assay. Anti-inflammatory effects of sumatriptan lead to decrease mortality rate and inflammatory cytokines in CLP induction sepsis in C57BL/6 mice.

Automated summary

Sepsis is a severe systemic inflammatory response with high mortality rate caused by different microorganisms. Sumatriptan, a 5-HT1B/1D agonist, has anti-inflammatory and anti-oxidative stress effects, showing significant protection in sepsis-induced inflammatory cytokines and survival rate.