Minocycline protects against hepatic ischemia/reperfusion injury in a rat model

Li,Yining; Li,Tao; Qi,Haizhi; Yuan,Fang

doi:10.3892/br.2014.381

Minocycline protects against hepatic ischemia/reperfusion injury in a rat model

Authors:
- Yining Li
- Tao Li
- Haizhi Qi
- Fang Yuan
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Affiliations: Organ Transplantation Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: November 11, 2014 https://doi.org/10.3892/br.2014.381
Pages: 19-24

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Abstract

Hepatic ischemia/reperfusion (I/R) injury is a common clinical problem. The present study was conducted to investigate the protective effect and mechanism of minocycline (Mino), a tetracycline with anti‑inflammatory and antioxidant properties, on I/R injury of liver in rats. In total, 54 male Sprague‑Dawley rats were randomly divided into 3 groups with 18 rats in each: Sham‑operated (control group), I/R model (I/R group) and Mino preconditioning groups (Mino group). The rats of the Mino group were administered Mino (45 mg/kg) by gastric irrigation at 36 h before surgery and were subsequently administered with 22.5 mg/kg every 12 h for the 36 h before surgery. The rats were sacrificed at 2, 6 and 24 h after reperfusion, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured. Hematoxylin/eosin staining of liver tissues was performed to detect the rat liver histological changes and the grade of liver I/R injury (Suzuki's criteria); the levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were determined by spectrophotometry; hepatic tumor necrosis factor‑α (TNF‑α) and interleukin‑1β (IL‑1β) mRNA were measured by quantitative polymerase chain reaction; the Dickkopf‑1 (DKK‑1) and β‑catenin gene products of the liver were detected by western blot analysis. Mino treatment significantly ameliorated the I/R injury of the liver, as shown by decreased Suzuki scores and liver function (ALT, AST and LDH). After 2, 6 and 24 h reperfusion, compared to the I/R group the MDA and MPO levels of the Mino group decreased in the liver tissues and the levels of hepatic TNF‑α and IL‑1β mRNA were decreased too. The protein expression of hepatic DKK‑1 decreased, whereas β‑catenin increased, which indicates that the Wnt/β‑catenin pathway has been activated. In conclusion, Mino protects the liver from I/R injury mainly through reducing oxidative stress and inhibiting the release of pro‑inflammatory cytokines by activating the Wnt/β‑catenin signaling pathway in the liver.

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