Effect of pyrogallol nanocomposite on miRNA and its associated pathways during radiation-induced toxicity in small intestine of irradiated Balb/C mice.

Abstract

Cancer is the abnormal and uncontrolled growth of cells that changes the structure of nearby cells or tissues. Cancer treatment strategies include surgery, chemotherapy, immunotherapy, and radiotherapy. Radiation therapy is one of the most frequently used cancer treatment modalities. Ionizing radiation not only kills cancer cells but also affects surrounding normal cells, causing extensive damage to all organs including the liver, kidneys, and intestines. Thus, identifying radioprotective agents is crucial to reduce the side effects of radiotherapy. Recently, nanocomposites have played a crucial role in cancer diagnosis and treatment as well as in reducing radiation-induced side effects. In this study, we tested pyrogallol nanocomposites for radiation-induced toxicity. Pyrogallol is a catechin molecule found in oak, eucalyptus, and other hardwood plants and is an amino polysaccharide produced by the deacetylation of chitin found in crustaceans and insects. In this study, pyrogallol and chitosan nanoparticles were blended to form a pyrogallol nanocomposite (PyNC). We investigated changes in miRNA expression in the small intestine of irradiated BALB/c mice. BALB/c mice were divided into four groups: control, irradiated (10 Gy), irradiated (10 Gy) + PyNC (40 μg/kg body weight), and PyNC alone (40 μg/kg body weight). We analyzed miRNA expression, apoptotic genes, inflammatory genes, and fibrotic genes using real-time PCR, and apoptotic proteins were analyzed by Western blotting and immunohistochemistry. Our results revealed that radiation modulated miRNA expression patterns regulated by PyNC. Analysis of the miRNA online database revealed that the miRNA targets were casp9, IL7, IL7R, JUN, MMP9, Bcl2, and SMAD4. Furthermore, real-time PCR, Western blotting, and immunohistochemistry analyses revealed that radiation increased apoptotic proteins, inflammatory markers, and TGF-β and its associated molecules, which effectively decreased upon PyNC treatment in irradiated BALB/c mice. Additionally, PyNC treatment inhibited DNA fragmentation and oxidative stress in the small intestine of irradiated BALB/c mice. Overall, we suggest that PyNC effectively protects the small intestine from radiation-induced toxicity by altering miRNAs and their associated molecular targets, including apoptosis, inflammation, and fibrosis. However, overexpression or knockout studies of miRNAs during radiation-induced toxicity are warranted.