Kupffer cell depletion by gadolinium chloride aggravates liver injury after brain death in rats

Zhu,Rongtao; Guo,Weizhi; Fang,Hongbo; Cao,Shengli; Yan,Bing; Chen,Sanyang; Zhang,Kaiming; Zhang,Shuijun

doi:10.3892/mmr.2018.8646

Kupffer cell depletion by gadolinium chloride aggravates liver injury after brain death in rats

Authors:
- Rongtao Zhu
- Weizhi Guo
- Hongbo Fang
- Shengli Cao
- Bing Yan
- Sanyang Chen
- Kaiming Zhang
- Shuijun Zhang
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Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The First Afﬁliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: February 27, 2018 https://doi.org/10.3892/mmr.2018.8646
Pages: 6357-6362
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Brain death (BD) impairs liver function in potential donors, and is associated with hormonal and metabolic changes or molecular effects with pro‑inflammatory activation. Resident macrophages in the liver named Kupffer cells (KCs) undergo pro‑ or anti‑inflammatory pathway activation, which affects liver function. However, the role of the KCs in liver dysfunction following BD has not been fully elucidated. The aim of the present study was to investigate the role of KCs in liver dysfunction in the context of BD and the effects of their inhibition by gadolinium chloride (GdCl3). Rats were randomly divided into the following groups: Control, BD with GdCl3 pretreatment and BD with normal saline pretreatment. Liver function, hepatic pathological histology and cytokine levels in the liver were assessed. Apoptosis and apoptosis‑related proteins [cleaved caspase‑3, caspase‑3 and apoptosis regulator Bcl‑2 (Bcl‑2)] were evaluated. GdCl3 significantly aggravated liver injury by elevating alanine aminotransferase and aspartate aminotransferase levels (P<0.05) by inhibiting KCs. Interleukin (IL)‑1β and tumor necrosis factor α levels in the GdCl3 group were significantly increased compared with those in the control and saline groups (P<0.01). However, IL‑10 levels in the GdCl3 group were significantly reduced compared with those in the saline group (P<0.05). Caspase‑3 and cleaved caspase‑3 activation, and apoptosis induction in the context of BD were also signiﬁcantly aggravated by the depletion of KCs, whereas Bcl‑2 was signiﬁcantly suppressed by the administration of GdCl3. The present study indicated that GdCl3 efficiently inhibits the activity of KCs, and is involved in the onset of liver injury through its effects on pro‑inflammatory and anti‑inflammatory activation. KCs are protective in the liver in the context of BD. This protection appears to be due to KCs secretion of the potent anti‑inflammatory cytokine IL‑10, suggesting that KCs are an attractive target for the prevention and treatment of liver injury in the context of BD in rats.

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