Pretreatment of Cisplatin in Recipients Attenuates Post-Transplantation Pancreatitis in Murine Model

Sheng Yan^{1, #}, Yuan Ding^{1, #}, Fei Sun¹, Zhongjie Lu¹, Liang Xue¹, Xiangyan Liu¹, Mingqi Shuai¹, Chen Fang¹, Yan Wang¹, Hui Cheng¹, Lin Zhou¹, Ming H Zheng^1,2,✉, Shusen Zheng^1,✉

1. Division of Hepatobiliary and Pancreatic Surgery; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health; and Key Laboratory of Organ Transplantation Zhejiang Province, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, P.R. China.
2. Centre for Orthopaedic Research, School of Surgery, University of Western Australia, Western Australia, 6009, Australia.
# These authors contributed equally to this paper.

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Citation:
Yan S, Ding Y, Sun F, Lu Z, Xue L, Liu X, Shuai M, Fang C, Wang Y, Cheng H, Zhou L, Zheng MH, Zheng S. Pretreatment of Cisplatin in Recipients Attenuates Post-Transplantation Pancreatitis in Murine Model. Int J Biol Sci 2012; 8(3):298-309. doi:10.7150/ijbs.3656. Available from http://www.ijbs.com/v08p0298.htm

Abstract

Pancreas transplantation is the definite treatment for type 1 diabetes that enables the achievement of long-term normoglycemia and insulin independence. However Post-Transplantation Pancreatitis (PTP) due to ischemia reperfusion (IR) injury and preservation is a major complication in pancreas transplantation. Owning the potential anti-inflammatory effect of Cisplatin (Cis) in liver IR injury, we have examined if Cis could attenuate PTP using a murine model. We found that Cis is able to prevent inflammatory response in PTP. Pretreatment of Cis in recipient mice reduce the impairments of the grafts and hyperamylasimea in the recipients. We documented that the protective mechanism of Cis in PTP involves improvement of microcirculation, reduction of the mononuclear cellular infiltration and apoptosis, suppression of inflammatory cytokine-cascade and inhibition of translocation of high-motility group box protein-1 (HMGB-1) from nucleus to cytoplasm. In short, our study demonstrated that pretreatment of Cis in recipients may reduce the onset of PTP in pancreas transplantation.

Keywords: Cisplatin, Pancreatitis, Ischemia reperfusion injury, High-motility group box protein-1, Intravital fluorescence microscopy.