Hesperidin - loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway.

Introduction: Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a bioflavonoid naturally occurring in citrus fruits, exhibits a range of pharmacological attributes, including antimicrobial, antioxidant, anti-inflammatory, anticoagulant, and analgesic properties. The main objective of the study was to formulate a hydrogel with the intention of addressing skin conditions, particularly wound healing. Methods: This research introduces a methodology for the fabrication of a membrane composed of a Polyvinyl alcohol - Sodium Alginate (PVA/A) blend, along with the inclusion of an anti-inflammatory agent, Hesperidin (H), which exhibits promising wound healing capabilities. A uniform layer of a homogeneous solution comprising PVA/A was cast. The process of crosslinking and the enhancement of hydrogel characteristics were achieved through the application of gamma irradiation at a dosage of 30 kGy. The membrane was immersed in a Hesperidin (H) solution, facilitating the permeation and absorption of the drug. The resultant system is designed to deliver H in a controlled and sustained manner, which is crucial for promoting efficient wound healing. The obtained PVA/AH hydrogel was evaluated for cytotoxicity, antioxidant and free radical scavenging activities, anti-inflammatory and membrane stability effect. In addition, its action on oxidative stress, and inflammatory markers was evaluated on BJ-1 human normal skin cell line. Results and Discussion: We determined the effect of radical scavenging activity PVA/A (49 %) and PVA/AH (87%), the inhibition of Human red blood cell membrane hemolysis by PVA/AH (81.97 and 84.34 %), hypotonicity (83.68 and 76.48 %) and protein denaturation (83.17 and 85.8 %) as compared to 250 µg/ml diclofenac (Dic.) and aspirin (Asp.), respectively. Furthermore, gene expression analysis revealed an increased expression of genes associated with anti-oxidant and anti-inflammatory properties and downregulated TNFα, NFκB, iNOS, and COX2 by 67, 52, 58 and 60%, respectively, by PVA/AH hydrogel compared to LPS-stimulated BJ-1 cells. The advantages associated with Hesperidin can be ascribed to its antioxidant and anti-inflammatory attributes. The incorporation of Hesperidin into hydrogels offers promise for the development of a novel, secure, and efficient strategy for wound healing. This innovative approach holds potential as a solution for wound healing, capitalizing on the collaborative qualities of PVA/AH and gamma irradiation, which can be combined to establish a drug delivery platform for Hesperidin.

The Implication of microRNAs as non-invasive biomarkers in 179 Egyptian breast cancer female patients.

Background: MicroRNAs (miRs) are small (19-25 nucleotides), non-protein coding RNAs that regulate gene expression, and thus play essential roles in cell cycle progression. The evidence has demonstrated that the expression of several miRs is dysregulated in human cancer. Methods: The study includes 179 female patients and 58 healthy women Patients were identified as luminal A, B, Her-2/neu, and basal-like, as well as classified into I, II, and III stages. Analysis of the expression fold change of miR-21 and miR-34a with molecular markers, including the oncogene Bcl-2 (B-cell lymphoma 2) and the tumor suppressor genes BRCA1 (breast cancer susceptibility gene 1), BRCA2 (breast cancer susceptibility gene 2), and the tumor suppressor protein p53, was carried out for all patients, pre- and post-chemotherapy, and for all healthy women. Results: At diagnosis (pre-chemotherapy), miR-21 was up-regulated (p < 0.001), while miR-34a was down-regulated (p < 0.001). Post-chemotherapy, the expression of miR-21 decreased significantly (p < 0.001), while the expression of miR-34a increased significantly (p < 0.001). Conclusion: miR-21 and miR-34a may be helpful to non-invasive biomarkers to evaluate the response of breast cancer to chemotherapy.

The impact of citicoline on brain injury in rats subjected to head irradiation.

Hazard and risk associated with the use of radiotherapy play a crucial role in brain injury with interference via the neuroendocrine activity of the cancer survivors, and there is no effective preventive strategy. We conducted this study to assess the effect of citicoline in biosynthesis variants occurring in the cerebral cortex of rats in response to head γ-irradiation. Bio-analysis includes MDA, 8-OHdG, and NO as oxidation indicators; total antioxidant activity; the inflammatory factors TNF-α, IL-1ß, and amyloid-ß 42 levels; the caspase-3 cell death marker; IGF-I; serum hormones including GH, ACTH, FSH, and LH; and the neurotransmitters acetylcholine, dopamine, and serotonin. We exposed animals to 10 Gy head gamma irradiation followed by citicoline treatment and sustained for 30 days. The animals were sacrificed at the 3rd and 30th day post-irradiation. Citicoline mechanism has been linked to potent radical reduced ability counteracting the oxidative stress-mediated inflammation and apoptosis. Citicoline treatment has normalized the altering recorded in serum hormones associated with a significant modulation in the levels of IGF-1/PI3K/AKT factors. Such improvements have been concomitant with regulated neurotransmitter levels. We could conclude that citicoline may safely be supplemented to avoid both short- and long-term damages to the neuroendocrine disturbances, oxidative stress, inflammation, and apoptosis induced by head irradiation.

Role of betaine in liver injury induced by the exposure to ionizing radiation.

Oxidative stress, apoptosis, and fibrosis may play a major role in the development of radiation-induced liver damage. Betaine, a native compound widely present in beetroot, was reported to possess hepato-protective properties. The objective of this study was to investigate the influence of betaine on radiation-induced liver damage. Animals were exposed to 9 Gy applied in 3 doses of 3 Gy/wk. Betaine (400 mg/kg/d), was orally supplemented to rats after the first radiation dose, and daily during the irradiation period. Animals were sacrificed 1 day after the last dose of radiation. The results showed that irradiation has induced oxidative stress in the liver denoted by a significant elevation in malondialdehyde, protein carbonyl, and 8-hydroxy-2-deoxyguanosine with a significant reduction in catalase activity and glutathione (GSH) content. The activity of the detoxification enzyme cytochrome P450 (CYP450) increased while GSH transferase (GSH-T) decreased. The activity of the apoptotic marker caspase-3 increased concomitant with increased hyaluronic acid, hydroxyproline, laminin (LN), and collagen IV. These alterations were associated with a significant increase of gamma-glutamyl transferase, alkaline phosphatase and alanine and aspartate aminotransferase markers of liver dysfunction. Betaine treatment has significantly attenuated oxidative stress, decreased the activity of CYP450, enhanced GSH-T, reduced the activity of caspase-3, and the level of fibrotic markers concomitant with a significant improvement of liver function. In conclusion, betaine through its antioxidant activity and by enhancing liver detoxification and reducing apoptosis may alleviate the progression of liver fibrosis and exert a beneficial impact on radiation-induced liver damage.

Fish oil omega-3 fatty acids reduce the severity of radiation-induced oxidative stress in the rat brain.

PURPOSE: To evaluate the modulator role of fish oil (FO) on some biochemical changes in the brain of gamma-irradiated rats (RAD). MATERIAL AND METHODS: Male albino rats Sprague Dawley were divided into four groups (n = 10). (i) CONTROL: received vehicle via gavages during 28 days; (ii) FO: received fish oil (400 mg/kg/day) via gavages during 28 days; (iii) RAD: received vehicle for 7 days before whole body gamma-irradiation with 8 Gy given in four fractions each 7 days apart and continued during the irradiation period; and (iv) FO+ RAD: received FO for 7 days before exposure to the first dose of irradiation and FO treatment was continued during the irradiation period. Animals were sacrificed 24 hours post the last irradiation dose. RESULTS: A significant increase of malondialdehyde (MDA) and protein carbonyl (CO) content associated with a significant decrease of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content were recorded in the brain of irradiated rats. Oxidative stress was accompanied by a significant decrease of eicosapentaenoic (EPA) and docosahexaenoic (DHA) levels. Aspartic (Asp) and glutamic (Glu) acid levels were increased. Serotonin level showed a decrease associated with enhanced monoamine oxidase (MAO) activity and increased 5-hydroxyindolacetic acid (5-HIAA) level. FO treatment reduced the severity of radiation-induced oxidative stress, alteration of Asp and Glu levels and serotonin metabolism concomitant with increased EPA and DHA levels. CONCLUSION: FO attenuates the severity of radiation-induced biochemical disorders in the brain by counteracting the radiation-induced decrease of EPA and DHA. Further studies are needed concerning the long-term implications of our findings.

Lycopene protects the structure of the small intestine against gamma-radiation-induced oxidative stress.

The small intestine displays numerous morphological and functional alterations after exposure to ionizing radiations. Oxidative stress and changes in monoamines levels may contribute toward some of these alterations. The objective of the current work is to evaluate the efficacy of lycopene on radiation-induced damage in the small intestine. Lycopene (5 mg/kg BW) was given to male albino rats, via gavages for 7 days before whole body exposure to gamma ray (6 Gy). Irradiated animals, sacrificed 7 days after irradiation, showed sloughing villi, ulcers, and ruptured goblet cells, shrinkage of submucosa layers, more fibers and fibroblasts. Histopathological changes were associated with a significant increase in thiobarbituric acid reactive substances (TBARS) and alteration in xanthine oxidoreductase system (XOR). In parallel, significant decreases in reduced glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT) activities were recorded. Gamma irradiation has also induced a significant decrease in the level of monoamines: serotonin (5-HT), dopamine (DA), norepinephrine (NE), and epinephrine (EPI) associated with an increase in monoamine-oxidase (MAO) activity. Lycopene pretreatment has significantly improved the oxidant/antioxidant status, which was associated with significant regeneration of the small intestine, and improved monoamines levels. Based on these results, it is concluded that lycopene may protect the small intestine against radiation-induced damage.

Grape seed extract Vitis vinifera protects against radiation-induced oxidative damage and metabolic disorders in rats.

Whole body exposure to ionizing radiation induces the formation of reactive oxygen species (ROS) in different tissues provoking oxidative damage, organ dysfunction and metabolic disturbances. The present study was designed to determine the possible protective effect of grape seed extract (GSE), rich in proanthocyanidins against gamma-radiation-induced oxidative stress in heart and pancreas tissues associated with serum metabolic disturbances. Irradiated rats were whole body exposed to 5 Gy gamma-radiation. GSE-treated irradiated rats received 100 mg GSE/kg/day, by gavage, for 14 days before irradiation. The animals were killed on days 1, 14 and 28 after irradiation. Significant decreases of SOD, CAT and GSH-Px activities associated with significant increases of TBARS levels were recorded in both tissues after irradiation. GSE administration pre-irradiation significantly attenuated the radiation-induced oxidative stress in heart tissues which was substantiated by a significant amelioration of serum LDH, CPK and AST activities. GSE treatment also attenuated the oxidative stress in pancreas tissues which was associated with a significant improvement in radiation-induced hyperglycemia and hyperinsulinemia. In conclusion, the present data demonstrate that GSE would protect the heart and pancreas tissues from oxidative damage induced by ionizing irradiation.

Role of lycopene in recovery of radiation induced injury to mammalian cellular organelles.

Whole body exposure of male rats to 7 Gy gamma irradiation increased lipid peroxidation in the liver resulting in biomembrane damage of subcellular structures and release of their enzymes. This is evidenced by increase of thiobarbituric acid-reactive substances (TBARS) in mitochondria, lysosomes and microsomes. This was associated with a decrease in activity of the enzymes specific for each subcellular fraction; namely, mitochondrial glutamate dehydrogenase (GDH), lysosomal beta-glucuronidase and microsomal glucose 6-phosphatase. This was paralleled by an increased activity of these enzymes in the cytosol. Rats were supplemented with lycopene, a carotenoid present in tomatoes (5 mg/kg weight/day), by gavage, for 7 days before exposure to 7 Gy gamma irradiation. This resulted in diminishing amount of TBARS recorded for each subcellular structure in the liver of irradiated animals. Significant amelioration in the decrease recorded for the activity of mitochondrial glutamate dehydrogenase, lysosomal beta-glucuronidase and microsomal glucose 6-phosphatase was observed. This was associated with significant amelioration in the increase recorded for the activity of these enzymes in the cytosol. It is postulated that lycopene could play an important role in the recovery of the integrity of biological membranes of the liver after radiation injury.