Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway

Molecular Medicine Reports
Shuai XueQifa Ye

Abstract

Hypothermic machine perfusion (HMP) has been demonstrated to be a more effective method for preserving livers donated after circulatory death (DCD) than cold storage (CS); however, the underlying mechanisms remain unclear. The aim of the present study was to investigate the protective effects of HMP on rat DCD livers and the possible role of the nuclear factor erythroid 2‑related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. A total of 18 adult male rats were randomly divided into three groups: Control, HMP and CS (n=6 per group). To simulate the conditions of DCD liver transplantation, rat livers in the CS and HMP groups were subjected to 30 min warm ischemia following cardiac arrest and were then preserved by CS or HMP for 3 h. Subsequently, after 1 h of isolated reperfusion, the extent of ischemia/reperfusion injury (IRI) and cellular functions were assessed. During reperfusion, intrahepatic resistance and bile production were measured, and the perfusion fluid was collected for liver enzyme analysis. The liver tissues were then harvested for the assessment of malondialdehyde (MDA) production, superoxide dismutase (SOD) activity, ATP levels, as well as for histological analysis, immunohistochemistry an...Continue Reading

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Citations

Mar 7, 2021·International Journal of Molecular Sciences·Laura Giuseppina Di PasquaMariapia Vairetti
Jul 25, 2021·International Journal of Molecular Sciences·George ClarkeDarius F Mirza

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