Dexmedetomidine alleviates hepatic injury via the inhibition of oxidative stress and activation of the Nrf2/HO-1 signaling pathway

Zhao, Yuan; Kong, Gaoyin; Pei, Wanmin; Zhou, Bo; Zhang, Qinqin; Pan, Bingbing

doi:10.1684/ecn.2019.0431

Cited by 24 publications

(2 citation statements)

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“…Hepatic involvement in i–IRI is well documented in the literature. 29 Beside the general mechanism of endothelium damage induced by activated lymphocytes in liver, kidneys or lungs, because of the anatomical relationship between the intestine and the liver, all the toxic substances accumulated during ischemia are drained directly to the liver through the portal vein adding more stress to the organ. Despite the positive effects on the intestine (both mucosal damage and absorptive function), none of the treatments employed was able to reduce the elevation of these enzymes.…”

Section: Discussionmentioning

confidence: 99%

“… 28 There is little evidence about the underlying mechanism of the protective effect of dexmedetomidine against oxidative stress, but it has been shown that it activates the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (NrF-2/HO-1) signaling pathways, protecting against oxidative stress-induced DNA damage and apoptosis. 29 Because of its promptness in peaking plasma concentrations (15 minutes) and its prolonged effect (up to 4 h), is a promising agent for treating i–IRI. 30 In fact, it was successfully used to prevent damage to the lungs 31 and liver 32 after i–IRI, and even to the intestine.…”

Section: Introductionmentioning

confidence: 99%

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Prophylactic Treatment of Intestinal Ischemia-Reperfusion Injury Reduces Mucosal Damage and Improves Intestinal Absorption

Garcia-Alonso,

Velasco-Oraa,

Cearra

et al. 2023

JIR

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Purpose Intestinal ischemia-reperfusion injury (i–IRI) involves a blood flow interruption in an intestinal segment followed by blood flow restoration. When blood flow is restored, oxidative and inflammatory molecules are distributed throughout the bloodstream, triggering both local and systemic damage. Our goal was to evaluate the potential of three antioxidant and/or anti–inflammatory compounds (curcumin, dexmedetomidine and α-tocopherol) to prevent or reverse local and systemic damage induced by i–IRI. Methods i-IRI was induced by placing a microvascular clip in the superior mesenteric artery of female WAG/RijHsd rats; the clip was removed after 1h and reperfusion was allowed for 4h. Curcumin (200 mg/kg, orally), α-tocopherol (20 mg/kg, i.p.), and dexmedetomidine (5 or 20 µg/kg, s.c.; DEX5 and DEX20, respectively) were administered. Blood and terminal ileum specimens were collected for biochemical and histological determination. Furthermore, D-xylose absorption test was performed to evaluate intestinal absorption; after completing the 1-hour ischemia and 4-hour reperfusion period, 1 mL of aqueous D-xylose solution (0.615 mg/mL) was administered orally, and one hour later, plasma D-xylose levels were quantified. Results The histological injury degree (HID) measured by the Chiu scale was significantly reduced when the treatments were applied (non-treated rats, 2.6 ± 0.75; curcumin, 1.54 ± 0.8; DEX5, 1.47 ± 0.7; DEX20 1.14 ± 0.5; and α-tocopherol, 1.01 ± 0.6); intestinal absorptive capacity also improved in all cases healthy rats (2.06 ± 0.07 µg/mL; non-treated, 1.18 ± 0.07 µg/mL; curcumin 1.76 ± 0.3 µg/mL; DEX5, 2.29 ± 0.2 µg/mL; DEX20, 2.25 ± 0.26 µg/mL; and α-tocopherol 1.66 ± 0.21 µg/mL). However, it failed to reduce liver enzyme levels. Finally, only dexmedetomidine significantly reduced urea and creatinine levels compared to non-treated animals. Conclusion All drugs were effective in reducing HID, although α-tocopherol was effective to a greater extent. Only dexmedetomidine reverted intestinal absorption to normal values of healthy animals.

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Section: Discussionmentioning

confidence: 99%