Cilostazol mitigates mesenteric ischemia/reperfusion-induced lung lesion: Contribution of PPAR-γ, NF-κB, and STAT3 crosstalk

Aims: Cilostazol (Cilo), a phosphodiesterase-III inhibitor, has signified its efficacy against different ischemia/ reperfusion (IS/RE) models. Nevertheless, it has not fully illuminated its potential effect against intestinal IS/REinduced lung injury. Consequently, the study was fashioned to evaluate the feasible mechanism of action of Cilo against intestinal IS/RE-induced lung injury. Main methods: Wistar rats were treated with Cilo (0.1 g/kg, p.o.) or with a vehicle for 14 days prior to IS/RE, induced by clamping of the superior mesenteric artery for 30 min with subsequent clamp removal for 2 h. Key findings: The mechanistic study disclosed that Cilo protected the two studied organs, viz., lung, and intestine partially by intensifying the expression/content of PPAR-gamma accompanied by reducing the expression/content of NF-kappa B-p65 and STAT3. In addition to normalizing MDA, iNOS, and NOx, the Cilo antioxidant power was confirmed by intensifying tissues content of the total antioxidant capacity. With regard to the anti-inflammatory effect, Cilo reduced the effects of TNF-alpha, IL-6, and ICAM-1, which were reflected in MPO activity. Furthermore, Cilo had an anti-apoptotic attribute demonstrated by enhancing Bcl-2 content and lessening caspase-3 level. Significance: Cilo provided conceivable protective mechanisms to modulate events concomitant with mesenteric IS/RE partly by modulating oxidative stress, inflammation, and apoptosis feasibly via the participation of PPAR-gamma, STAT3, and NF-kappa B p65 signaling pathways.

Automated summary

Cilostazol, a phosphodiesterase-III inhibitor, has been shown to have protective effects against intestinal ischemia/reperfusion-induced lung injury, partly by modulating oxidative stress, inflammation, and apoptosis mechanisms.