A narrative review of the protective effects of curcumin in treating ischemia-reperfusion injury.

Background and Objective: Ischemia-reperfusion (IR) injury is the cause of morbidity and mortality in a variety of diseases and surgical procedures including organ transplantation surgeries, acute coronary syndrome, strokes, and limb injuries. IR injury causes dysfunction of tissues and organs, and oxidative stress plays an important role in driving this process. Curcumin (CUR), a polyphenolic compound derived from turmeric, protects against IR injury by alleviating oxidative stress, reactive oxygen species (ROS) inflammation, apoptosis, and fibrosis. We review the protective effects of CUR against IR. Methods: We searched PubMed, ScienceDirect, and Web of Science databases using the keywords: ischemic reperfusion, CUR and summarized the results. Key Content and Findings: The effects of CUR during IR have been reported for animal models in vitro and in vivo and the compound has been shown in various organs by suppression of oxidative stress, prevention of inflammation, inhibition of apoptosis and autophagy. CUR with nanocarriers showed many advantages than free CUR in the treatment of IR injury, such as improved bioavailability, sustained-release, better water solubility, better target organ accumulation, improved permeability across the blood-brain-barrier and more effective. Conclusions: Nanotechnology offers significant improvements and promising strategies to improve drug delivery to IR-injured tissues and achieve the desired protective effects. Thus, it is necessary to promote further clinical trials to promote the clinical application of CUR with nanocarriers.

Characterization, efficacy, pharmacokinetics, and biodistribution of 5kDa mPEG modified tetrameric canine uricase variant.

PEGylated uricase is a promising anti-gout drug, but the only commercially marketed 10kDa mPEG modified porcine-like uricase (Pegloticase) can only be used for intravenous infusion. In this study, tetrameric canine uricase variant was modified by covalent conjugation of all accessible ɛ amino sites of lysine residues with a smaller 5kDa mPEG (mPEG-UHC). The average modification degree and PEGylation homogeneity were evaluated. Approximately 9.4 5 kDa mPEG chains were coupled to each monomeric uricase and the main conjugates contained 7-11 mPEG chains per subunit. mPEG-UHC showed significantly therapeutic or preventive effect on uric acid nephropathy and acute urate arthritis based on three different animal models. The clearance rate from an intravenous injection of mPEG-UHC varied significantly between species, at 2.61 mL/h/kg for rats and 0.21 mL/h/kg for monkeys. The long elimination half-life of mPEG-UHC in non-human primate (191.48 h, intravenous injection) indicated the long-term effects in humans. Moreover, the acceptable bioavailability of mPEG-UHC after subcutaneous administration in monkeys (94.21%) suggested that subcutaneous injection may be regarded as a candidate administration route in clinical trails. Non-specific tissue distribution was observed after administration of (125)I-labeled mPEG-UHC in rats, and elimination by the kidneys into the urine is the primary excretion route.