AUTHOR=Sonmez Muhammed Ikbal , Shahzadi Andleeb , Kose Cagla , Sonmez Haktan , Ozyazgan Sibel , Akkan Ahmet Gokhan 

TITLE=Effect of sulfasalazine on endothelium-dependent vascular response by the activation of Nrf2 signalling pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.979300

DOI=10.3389/fphar.2022.979300

ISSN=1663-9812

ABSTRACT=Background: Diabetes mellitus leads to endothelial dysfunction and accumulation of oxygen
radicals. Sulfasalazine-induced Nrf2 activation reduces oxidative stress in vessels. Thus, in the
present study we investigated the effects of sulfasalazine on endothelial dysfunction induced by
high glucose we also elucidated the underlying mechanism involved in glucose-induced
endothelial dysfunction.
Methods: For this experiment we used rat aorta to calculate the dose response curve of
noradrenalin and acetylcholine. Vessels were incubated in normal and high glucose (44mM) for
two hours. To investigate glucose and sulfasalazine effects the vessels of the high glucose group
were pre-treated with sulfasalazine, JNK inhibitor (SP600125), and ERK inhibitor (U0126) for
30 minutes. The eNOS, TAS, TOS, and HO-1 levels were estimated by commercially available
ELISA kits.
Results: In the high glucose group, the E max for contraction was significantly higher (p <0.001),
than the E max for relaxation. These functional changes were parallel with the low levels of eNOS
(p <0.05). High glucose vessel treated with sulfasalazine showed low E max value for contraction
(p <0.001) however, the E max for relaxation was significantly high (p <0.001). In the JNK group,
E max for contraction and relaxation was inhibited (p <0.001) compared to sulfasalazine treated
vessels. HO – 1 enzyme levels were significantly low (p <0.01) with sulfasalazine but higher
with ERK inhibitor (p <0.05).
Conclusion: High glucose induced endothelial dysfunction and sulfasalazine reduced damage in
high glucose vessels by activating eNOS, antioxidant effect, and particularly inducing Nrf2 via
the ERK and JNK pathways.