ABSTRACT
Background: Oral administration of proteins/peptides is challenging in clinical application due to their instability and susceptibility in the gastrointestinal tract. Materials and Methods: The in situ polymerization on the surface of enzymes was used to encapsulate antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) in polymeric shells, and the reactive oxygen species (ROS) scavenging ability was monitored based on DCFH-DA probe using flow cytometry and confocal laser scanning microscopy. The mRNA expression level of pro-inflammatory factors was assessed by real-time qPCR, using lipopolysaccharide-induced RAW264.7 cells as a model. Finally, the enzyme capsules were orally administered for the treatment of inflammatory bowel disease using dextran sodium sulfate (DSS)-induced colitis mice as a model, based on the evaluation of the disease-associated index, ROS level and pro-inflammatory cytokines' expression. Results: The enzyme capsules could effectively scavenge the intracellular reactive oxygen species (ROS) through the cascade catalysis of SOD and CAT, and thus protect the cells from ROS-induced oxidative damage. Meanwhile, the enzyme capsules could inhibit the secretion of pro-inflammatory cytokines from macrophages, thereby achieving favorable anti-inflammation effect. Oral administration of enzyme capsules could facilitate the accumulation of enzymes in the inflamed colon tissues of DSS-induced colitis mice. Moreover, the oral delivery of enzyme capsules could effectively alleviate the symptoms associated with colitis, attributing to the excellent ROS scavenging ability and the inhibition of pro-inflammatory cytokines' level. Conclusion: In summary, our findings provided a promising approach to construct enzyme-based nano-formulations with favorable therapeutic efficacy and biocompatibility, exhibiting great potential in the treatment of gastrointestinal diseases in an oral administration manner.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Mice , Animals , Dextran Sulfate , Reactive Oxygen Species/metabolism , Catalase , Antioxidants/pharmacology , Lipopolysaccharides , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/drug therapy , Cytokines/metabolism , Superoxide Dismutase/metabolism , Administration, Oral , RNA, MessengerABSTRACT
ABSTRACT: Heavy metals are an indispensable part of industrial and agricultural development. As the cradle of China's industry and an important province for agricultural production, Jilin Province has been an area of concern about heavy metal pollution in the local environment and grains. In this study, we focused on four heavy metals that are harmful to humans: arsenic (As), cadmium (Cd), methylmercury (MeHg), and inorganic arsenic (iAs). We determined the contents of these metals in 341 grain samples by using graphite furnace atomic absorption spectrometry and liquid chromatography-atomic fluorescence spectrometry and compared our results with the limit value of national standards. To evaluate the potential risk to human health, we determined the target hazard quotient and hazard index. Heavy metals were detected at these rates, from high to low: Cd (48%) > iAs (20.8%) > MeHg (4.6%) > Pb (3%). Most of these values are far below the limit of national standards. The target hazard quotient and hazard index were both smaller than 1; thus, we conclude that heavy metal pollution in grains in Jilin Province is not serious and that people are not at high risk from heavy metals in grains.
