Ameliorative effect of umbelliferone in remote organ injury induced by renal ischemia-reperfusion in rats

We evaluated the ameliorative role of umbelliferone in kidney, heart, and lung damage induced by renal ischemia/reperfusion (I/R) injury in rats. Umbelliferone was given orally to rats 60 min before ischemia. Ischemia was induced for 50 min and then reperfusion for 3 hr. The antioxidant enzymes, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, and cytokine levels in the kidney, heart, and lung were measured by ELISA. Moreover, histopathological changes were monitored. Renal I/R-induced oxidative stress in the organs by decreasing antioxidant enzymes. However, umbelliferone pretreatment enhanced superoxide dismutase (SOD) and glutathione (GSH), levels, reduced MDA and MPO levels. Renal I/R increased in tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) levels, and histopathological changes but these effects were inhibited with umbelliferone pretreatment. Furthermore, umbelliferone increased in nitric oxide synthase (eNOS) level under ischemia conditions. Our results indicated that pretreatment of umbelliferone-ameliorated damages in remote organ induced by renal I/R through suppressing oxidative stress and modulating inflammatory responses. Practical applications kidney, heart, and lung damages induced by renal I/R in rats was alleviated by umbelliferone. The oral treatment of umbelliferone markedly reversed the oxidative stress, inflammation, and histopathological changes by increasing in the levels of SOD, GSH, and eNOS, decreasing in the levels of MDA, MPO, TNF-alpha, and IL-6 in distant organ injury induced by renal I/R. This study firstly revealed that umbelliferone has potent antioxidant and anti-inflammatory activity in the remote organ damages caused by renal I/R. Consequently, umbelliferone may be an alternative therapeutic agent for treating renal I/R-induced damages.