Gallic Acid-Loaded Microemulsion Combined with Low Doses of Radiation Ameliorates Chronic Pancreatitis in Rats via Modulation of the Nrf2-Keap1-HO-1 Pathway

Document Type : Original Article

Authors

1 Health Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.

2 Polymer Chemistry Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.

3 Radiation Biology Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.

Abstract

Chronic pancreatitis (CP) is a complicated inflammatory disease with a significantly reduced quality of life and irreversible pancreatic damage. Gallic acid (GA), a common secondary polyphenol metabolite generated from plants, stimulated nuclear translocation of Nrf2 as well as the production of target proteins such as heme oxygenase-1 (HO-1). However, its usage is restricted due to its low water solubility, which results in poor bioavailability. So, in the current study, the microemulsions (MEs) were prepared based on polyvinylpyrrolidone polymer (PVP) as a carrier for GA to increase its miscibility and bioavailability. Also, characterization of polymer ME system was evaluated by using FTIR and DLS, in addition to studying its antimicrobial activity toward some types of bacteria. The objective of this research was to evaluate the effect of PVP/GA microemulsion prepared with clove oil essential oil (CEO) combined with low doses of radiation to ameliorate chronic pancreatitis in rats via modulation of the Nrf2/Keap1/HO-1 Pathway. 42 rats were randomly assigned to seven groups: control group, rats were received PVP/CEO/GA microemulsion (0.9 ml/100 g body weight) orally 5 days per week for 4 weeks, rats were exposed to low doses of radiation (0.25 Gy every week for 4 weeks), rats were received L-arginine 4 times by a dose of 250 mg/100 g body weight (2 doses separated by 1-hour interval), every week for 4 weeks to induce chronic pancreatitis, rats were received L-arginine & were received GA-loaded PVP/CEO microemulsion, rats were received L-arginine & were exposed to low doses of radiation, and rats were received L-arginine & were received GA-loaded PVP/CEO microemulsion & were exposed to low doses of radiation. L-arginine induced a marked increase in serum lipase, amylase, and lactate dehydrogenase (LDH) activities, MYD88, TLR4 gene expression, and IL-1β. While, a significant decrease in Nrf2, Keap1, and HO-1 was observed. GA-loaded PVP/Clove oil microemulsion significantly ameliorated the above-mentioned parameters and histopathological examination.

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