The effects of acute sumatriptan treatment on renal ischemia/reperfusion injury in rat and the possible involvement of nitric oxide

Can J Physiol Pharmacol. 2020 Apr;98(4):252-258. doi: 10.1139/cjpp-2019-0301. Epub 2019 Oct 11.

Abstract

Renal ischemia/reperfusion (I/R) injury is a common pathological condition. Studies reported renal toxicity following administration of triptans, which are commonly used for treating migraine headaches. To investigate the effects of sumatriptan and the molecular mechanisms involved in renal I/R injury in rats, ischemia was induced by bilateral clamping of renal pedicles followed by 24 h of reperfusion. Sumatriptan was administered in three different doses (5, 10, and 20 mg/kg) before I/R injury induction. Biochemical and histopathological changes were evaluated. The contribution of nitric oxide in modulating the effects of sumatriptan was determined by administrating aminoguanidine at 50 mg/kg 60 min before I/R injury. The tissue level of nitrite, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured. Sumatriptan at 10 and 20 mg/kg increased the serum level of creatinine (Cr) and blood urea nitrogen (BUN) significantly. There was also a significant increase in nitrite level of animals that received 10 mg/kg sumatriptan. Co-administration of sumatriptan with aminoguanidine significantly decreased the BUN and Cr. Depletion of SOD level (P < 0.05) and elevation of serum levels of MDA (P < 0.001) indicated the involvement of oxidative stress in sumatriptan adverse effects. Overall, the administration of sumatriptan intensified renal I/R injury through activation of inducible nitric oxide synthase and oxidative responses in rats.

Keywords: ischemia/reperfusion; ischémie/reperfusion; kidney; nitric oxide; oxyde nitrique; rat; rein; sumatriptan.

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / metabolism
  • Animals
  • Blood Urea Nitrogen
  • Creatinine / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Nitric Oxide / metabolism*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Sumatriptan / pharmacology*
  • Superoxide Dismutase / metabolism

Substances

  • Nitric Oxide
  • Malondialdehyde
  • Sumatriptan
  • Creatinine
  • Superoxide Dismutase