Bilirubin Improves the Quality and Function of Hypothermic Preserved Islets by Its Antioxidative and Anti-inflammatory Effect

Abstract

Background. Islet transplantation is a promising option for the treatment of type 1 diabetes. However, the current lack of practical techniques for the isolated islets preservation still hampers the advancement of life-saving islet transplantation. Islet suffers from internal or external stimuli-induced oxidative stress and subsequent inflammation during preservation, which leads to disappointing outcomes regarding islet yield, survival, and function. Reactive oxygen species (ROS) overproduction is the primary cause of oxidative stress that induces islet loss and dysfunction. Thus, in this article, we hypothesized that an endogenous antioxidant, bilirubin, that could efficiently scavenge ROS and inhibit inflammatory reactions could be beneficial for islet preservation. Methods. Herein, we studied the effect of bilirubin on the hypothermic preserved (4°C) islets and evaluate the islets viability, insulin secretory function, oxidative stress levels, and in vivo transplantation performance. Results. Bilirubin could prevent cellular damages during short-term preservation and maintain the cocultured islets viability and function. The protective role of bilirubin is associated with its antioxidative ability, which dramatically increased the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and decreased the levels of ROS and malondialdehyde. Diabetic mice transplanted with bilirubin preserved islets were normoglycemic for 28 days, even overmatched the diabetic mouse transplanted with fresh islets. Mice receiving bilirubin cocultured islets required the least time to achieve normoglycemia among all groups and exhibited minimum inflammatory responses during the early transplantation stage. Conclusions. By utilizing bilirubin, we achieved highly viable and functional islets after hypothermic preservation to reverse diabetes in mice.

Low Antioxidant Status of Serum Uric Acid, Bilirubin, Albumin, and Creatinine in Patients With Benign Paroxysmal Positional Vertigo

“…Many studies have reported a negative association between BIL levels and a range of diseases associated with oxidative stress, such as diabetes (27), asthma (28), and inflammatory bowel disease (29). Yao et al found that short-term preservation of BIL could prevent cell damage and maintain the viability and function of transplanted islets (30). The results of the present study also revealed lower BIL levels in the BPPV group with statistical differences between males and females.…”

Bioinspired biliverdin/silk fibroin hydrogel for antiglioma photothermal therapy and wound healing

“…Biliverdin, as one main component in the BVSF hydrogel system, also contributed to the wound repair. Our previous research indicated that bilirubin possesses a power anti-inflammatory property, which showed significant cytoprotective effects against oxidative and inflammatory damage in multiple cell lines 40 , 63 - 65 . Biliverdin, as a precursor substance of bilirubin, has also been demonstrated as an important cytoprotective and anti-inflammatory molecule 34 , 35 .…”

Drug discovery and formulation development for acute pancreatitis

“…In recent years, a large number of active drugs have emerged to improve therapy for acute pancreatitis by inhibiting the NF-κB signaling pathway in experiments (Cen et al., 2016 ; Tao et al., 2019 ). Bilirubin is a bioproduct, and possessed potent antioxidant and anti-inflammatory properties (Yao, Jiang, et al., 2019 ; Yao, Jiang, 2019 ; Yao, Huang, 2020 ; Yao, Sun, 2020 ). Our previous study also indicated that bilirubin could inhibit the NF-κB mediated pro-inflammatory signaling pathway, and significant reduced the progression of acute pancreatitis in a rat model (Wang et al., 2016 ).…”

“…Nanotechnology has gained considerable attention as a drug delivery carrier (Kou et al., 2013 , 2017a , 2017b , 2018a , 2018b , 2018c ). One of the most well-known benefits of nanomedicine is their selective accumulation by the enhanced permeability and retention (EPR) effect at tumor sites (Yao et al., 2018 ; Kou et al., 2019 ; Yao et al., 2019 , 2020 ; Zhao et al., 2020 ). Recent studies have indicated that similar EPR effect also occurred in the inflammatory lesion, that analogous nanoparticles within certain size range could accumulate in the inflamed site through the effect of extravasation across leaky vasculature and subsequent inflammatory cell-mediated sequestration, so-called ELVIS effect (Gong et al., 2019 ).…”

“…As mentioned above, the over premature release trypsin is one of the pathological features in acute pancreatitis. The over accumulated enzymes act as a stimulus for the nanoparticulate delivery system and could be utilized for controlled drug release (Yao et al., 2018 ; Qiao et al., 2019 ; Yao et al., 2019 ). Scientists have designed novel specific lipase-responsive nanoparticles as pancreatitis diagnostic agent (HW et al., 2014 ).…”